Science.gov

Sample records for allergic airway sensitization

  1. Airway Epithelial Regulation of Allergic Sensitization in Asthma

    PubMed Central

    Poynter, Matthew E.

    2012-01-01

    While many of the contributing cell types and mediators of allergic asthma are known, less well understood are the factors that influence the development of allergic responses that lead to the development of allergic asthma. As the first airway cell type to respond to inhaled factors, the epithelium orchestrates downstream interactions between dendritic cells (DCs) and CD4+ T cells that quantitatively and qualitatively dictate the degree and type of the allergic asthma phenotype, making the epithelium of critical importance for the genesis of allergies that later manifest in allergic asthma. Amongst the molecular processes of critical importance in airway epithelium is the transcription factor, nuclear factor-kappaB (NF-κB). This review will focus primarily on the genesis of pulmonary allergies and the participation of airway epithelial NF-κB activation therein, using examples from our own work on nitrogen dioxide (NO2) exposure and genetic modulation of airway epithelial NF-κB activation. In addition, the mechanisms through which Serum Amyloid A (SAA), an NF-κB-regulated, epithelial-derived mediator, influences allergic sensitization and asthma severity will be presented. Knowledge of the molecular and cellular processes regulating allergic sensitization in the airways has the potential to provide powerful insight into the pathogenesis of allergy, as well as targets for the prevention and treatment of asthma. PMID:22579987

  2. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

    SciTech Connect

    Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema; Akhtar, Mohamad Nadeem; Shaari, Khozirah; Zamri-Saad, Mohamad; Tham, Chau Ling; Sulaiman, Mohd Roslan; Lajis, Nordin Hj; Israf, Daud Ahmad

    2012-03-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.

  3. Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation

    SciTech Connect

    Kato, Takuma; Tada-Oikawa, Saeko; Wang, Linan; Murata, Mariko; Kuribayashi, Kagemasa

    2013-11-15

    In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases. - Highlights: • Oral exposure to TBT exacerbates airway inflammation. • TBT induces oxidative stress in secondary lymphoid organs, but not in the lung. • TBT preferentially induces regulatory T cell apoptosis over non-Treg cells. • TBT does not enhance pre-existing airway inflammation in sensitized mice. • Chemicals in food contaminants

  4. IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization

    NASA Astrophysics Data System (ADS)

    Mäkelä, M. J.; Kanehiro, A.; Borish, L.; Dakhama, A.; Loader, J.; Joetham, A.; Xing, Z.; Jordana, M.; Larsen, G. L.; Gelfand, E. W.

    2000-05-01

    Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10/) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.

  5. Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

    PubMed Central

    2010-01-01

    Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed. PMID:20092634

  6. Effect of diesel exhaust particles on allergic reactions and airway responsiveness in ovalbumin-sensitized brown Norway rats.

    PubMed

    Dong, Caroline C; Yin, Xuejun J; Ma, Jane Y C; Millecchia, Lyndell; Wu, Zhong-Xin; Barger, Mark W; Roberts, Jenny R; Antonini, James M; Dey, Richard D; Ma, Joseph K H

    2005-11-01

    We have previously demonstrated that exposure to diesel exhaust particles (DEP) prior to ovalbumin (OVA) sensitization in rats reduced OVA-induced airway inflammation. In the present study, Brown Norway rats were first sensitized to OVA (42.3 +/- 5.7 mg/m3) for 30 min on days 1, 8, and 15, then exposed to filtered air or DEP (22.7 +/- 2.5 mg/m3) for 4 h/day on days 24-28, and challenged with OVA on day 29. Airway responsiveness was examined on day 30, and animals were sacrificed on day 31. Ovalbumin sensitization and challenge resulted in a significant infiltration of neutrophils, lymphocytes, and eosinophils into the lung, elevated presence of CD4+ and CD8+ T lymphocytes in lung draining lymph nodes, and increased production of serum OVA-specific immunoglobulin (Ig)E and IgG. Diesel exhaust particles pre-exposure augmented OVA-induced production of allergen-specific IgE and IgG and pulmonary inflammation characterized by marked increases in T lymphocytes and infiltration of eosinophils after OVA challenge, whereas DEP alone did not have these effects. Although OVA-sensitized rats showed modest response to methacholine challenge, it was the combined DEP and OVA exposure that produced significant airway hyperresponsiveness in this animal model. The effect of DEP pre-exposure on OVA-induced immune responses correlated with an interactive effect of DEP with OVA on increased production of reactive oxygen species (ROS) and nitric oxide (NO) by alveolar macrophages (AM) and alveolar type II (ATII) cells, NO levels in bronchoalveolar lavage fluid, the induction of inducible NO synthase expression in AM and ATII cells, and a depletion of total intracellular glutathione (GSH) in AM and lymphocytes. These results show that DEP pre-exposure exacerbates the allergic responses to the subsequent challenge with OVA in OVA-sensitized rats. This DEP effect may be, at least partially, attributed to the elevated generation of ROS in AM and ATII cells, a depletion of GSH in AM and

  7. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  8. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.

    PubMed

    Talbot, Sébastien; Abdulnour, Raja-Elie E; Burkett, Patrick R; Lee, Seungkyu; Cronin, Shane J F; Pascal, Maud A; Laedermann, Cedric; Foster, Simmie L; Tran, Johnathan V; Lai, Nicole; Chiu, Isaac M; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M; Kuchroo, Vijay K; Bean, Bruce P; Levy, Bruce D; Woolf, Clifford J

    2015-07-15

    Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  9. Silencing nociceptor neurons reduces allergic airway inflammation

    PubMed Central

    Talbot, Sébastien; Abdulnour, Raja-Elie E.; Burkett, Patrick R.; Lee, Seungkyu; Cronin, Shane J.F.; Pascal, Maud A.; Laedermann, Cedric; Foster, Simmie L.; Tran, Johnathan V.; Lai, Nicole; Chiu, Isaac M.; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M.; Kuchroo, Vijay K.; Bean, Bruce P.; Levy, Bruce D.; Woolf, Clifford J.

    2015-01-01

    Summary Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8+ sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large pore ion channels to specifically block nociceptors, substantially reduced ovalbumin or house dust mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4+ and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  10. Innate Immune Responses to Engineered Nanomaterials During Allergic Airway Inflammation

    NASA Astrophysics Data System (ADS)

    Shipkowski, Kelly Anne

    The field of nanotechnology is continually advancing, and increasing amounts of consumer goods are being produced using engineered nanomaterials (ENMs). The health risks of occupational and/or consumer exposure to ENMs are not completely understood, although significant research indicates that pulmonary exposure to nanomaterials induces toxic effects in the lungs of exposed animals. Multi-walled carbon nanotubes (MWCNTs) are a specific category of ENMs and consist of sheets of graphene rolled into cylinders that are multiple layers thick in order to strengthen their rigidity. MWCNTs have a fiber-like shape, similar to that of asbestos, which allows for a high aspect ratio and makes them difficult to clear from the lung. Studies with rodent models have demonstrated that pulmonary exposure to ENMs, in particular MWCNTs, results in acute lung inflammation and the subsequent development of chronic fibrosis, suggesting a potential human health risk to individuals involved in the manufacturing of products utilizing these nanomaterials. Induction of IL-1beta secretion via activation of the inflammasome is a prime mechanism of MWCNT-induced inflammation. The inflammasome is a multi-protein scaffold found in a variety of cell types that forms in response to a variety of immune signals, including particulates. Sensitization with allergens, such as house dust mite (HDM), increases levels of the T helper 2 (Th2) cytokines IL-4 and IL-13 in mice and in humans, and there is particular cause for concern in cases of MWCNT exposure in individuals with pre-existing allergic airway disease, such as asthma. MWCNT exposure exacerbates airway inflammation and fibrosis in animal models of pre-existing allergic asthma, suggesting that individuals suffering from asthma are more susceptible to the toxic pulmonary effects of MWCNT exposure. Asthma is an exceptionally prominent human disease, and therefore the goal of this research was to better understand how pre-existing allergic airway

  11. NEUROTROPHIN MEDIATION OF ALLERGIC AIRWAYS RESPONSES TO INHALED DIESEL PARTICLES IN MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway hyper-responsiveness. Diesel exhaust particulates (DEP) associated with the combustion of diesel fuel exacerbate many of these allergic airways respons...

  12. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  13. Prevention of House Dust Mite Induced Allergic Airways Disease in Mice through Immune Tolerance

    PubMed Central

    Agua-Doce, Ana; Graca, Luis

    2011-01-01

    Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens. PMID:21818308

  14. Airway Fibrinogenolysis and the Initiation of Allergic Inflammation

    PubMed Central

    Millien, Valentine Ongeri; Lu, Wen; Mak, Garbo; Yuan, Xiaoyi; Knight, J. Morgan; Porter, Paul; Kheradmand, Farrah

    2014-01-01

    The past 15 years of allergic disease research have produced extraordinary improvements in our understanding of the pathogenesis of airway allergic diseases such as asthma. Whereas it was previously viewed as largely an immunoglobulin E-mediated process, the gradual recognition that T cells, especially Type 2 T helper (Th2) cells and Th17 cells, play a major role in asthma and related afflictions has inspired clinical trials targeting cytokine-based inflammatory pathways that show great promise. What has yet to be clarified about the pathogenesis of allergic inflammatory disorders, however, are the fundamental initiating factors, both exogenous and endogenous, that drive and sustain B- and T-cell responses that underlie the expression of chronic disease. Here we review how proteinases derived from diverse sources drive allergic responses. A central discovery supporting the proteinase hypothesis of allergic disease pathophysiology is the role played by airway fibrinogen, which in part appears to serve as a sensor of unregulated proteinase activity and which, when cleaved, both participates in a novel allergic signaling pathway through Toll-like receptor 4 and forms fibrin clots that contribute to airway obstruction. Unresolved at present is the ultimate source of airway allergenic proteinases. From among many potential candidates, perhaps the most intriguing is the possibility such enzymes derive from airway fungi. Together, these new findings expand both our knowledge of allergic disease pathophysiology and options for therapeutic intervention. PMID:25525732

  15. Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model.

    PubMed

    de Haar, Colin; Hassing, Ine; Bol, Marianne; Bleumink, Rob; Pieters, Raymond

    2005-10-01

    To gain more insight into the mechanisms of particulate matter (PM)-induced adjuvant activity, we studied the kinetics of airway toxicity/inflammation and allergic sensitization to ovalbumin (OVA) in response to ultrafine carbon black particles (CBP). Mice were exposed intranasally to OVA alone or in combination with different concentrations of CBP. Airway toxicity and inflammation were assessed at days 4 and 8. Immune adjuvant effects were studied in the lung draining peribronchial lymph nodes (PBLN) at day 8. Antigen-specific IgE was measured at days 21 and 28, whereas allergic airway inflammation was studied after OVA challenges (day 28). Results show that a total dose of 200 microg CBP per mouse, but not 20 microg or 2 microg, induced immediate airway inflammation. This 200 microg CBP was the only dose that had immune adjuvant activity, by inducing enlargement of the PBLN and increasing OVA-specific production of Th2 cytokines (IL-4, IL-5, and IL-10). The immune adjuvant activity of 200 microg CBP dosing was further examined. Whereas increased OVA-specific IgE levels in serum on day 21 confirms systemic sensitization, this was further supported by allergic airway inflammation after challenges with OVA. Our data show a link between early airway toxicity and adjuvant effects of CBP. In addition, results indicate that local cytokine production early after exposure to CBP is predictive of allergic airway inflammation. In addition this model appears suitable for studying the role of airway toxicity, inflammation and other mechanisms of particle adjuvant activity, and predicting the adjuvant potential of different particles.

  16. Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice

    PubMed Central

    2013-01-01

    Background With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. Methods We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. Results Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. Conclusions These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon

  17. Elimination of Aspergillus fumigatus conidia from the airways of mice with allergic airway inflammation

    PubMed Central

    2013-01-01

    Background Aspergillus fumigatus conidia can exacerbate asthma symptoms. Phagocytosis of conidia is a principal component of the host antifungal defense. We investigated whether allergic airway inflammation (AAI) affects the ability of phagocytic cells in the airways to internalize the resting fungal spores. Methods Using BALB/c mice with experimentally induced AAI, we tested the ability of neutrophils, macrophages, and dendritic cells to internalize A. fumigatus conidia at various anatomical locations. We used light microscopy and differential cell and conidium counts to determine the ingestion potential of neutrophils and macrophages present in bronchoalveolar lavage (BAL). To identify phagocyte-conidia interactions in conducting airways, conidia labeled with tetramethylrhodamine-(5-(and-6))-isothiocyanate were administered to the oropharyngeal cavity of mice. Confocal microscopy was used to quantify the ingestion potential of Ly-6G+ neutrophils and MHC II+ antigen-presenting cells located in the intraepithelial and subepithelial areas of conducting airways. Results Allergen challenge induced transient neutrophil recruitment to the airways. Application of A. fumigatus conidia at the acute phase of AAI provoked recurrent neutrophil infiltration, and consequently increased the number and the ingestion potential of the airway neutrophils. In the absence of recurrent allergen or conidia provocation, both the ingestion potential and the number of BAL neutrophils decreased. As a result, conidia were primarily internalized by alveolar macrophages in both AAI and control mice at 24 hours post-inhalation. Transient influx of neutrophils to conducting airways shortly after conidial application was observed in mice with AAI. In addition, the ingestion potential of conducting airway neutrophils in mice with induced asthma exceeded that of control mice. Although the number of neutrophils subsequently decreased, the ingestion capacity remained elevated in AAI mice, even at 24

  18. Innate Immune Responses to Engineered Nanomaterials During Allergic Airway Inflammation

    NASA Astrophysics Data System (ADS)

    Shipkowski, Kelly Anne

    The field of nanotechnology is continually advancing, and increasing amounts of consumer goods are being produced using engineered nanomaterials (ENMs). The health risks of occupational and/or consumer exposure to ENMs are not completely understood, although significant research indicates that pulmonary exposure to nanomaterials induces toxic effects in the lungs of exposed animals. Multi-walled carbon nanotubes (MWCNTs) are a specific category of ENMs and consist of sheets of graphene rolled into cylinders that are multiple layers thick in order to strengthen their rigidity. MWCNTs have a fiber-like shape, similar to that of asbestos, which allows for a high aspect ratio and makes them difficult to clear from the lung. Studies with rodent models have demonstrated that pulmonary exposure to ENMs, in particular MWCNTs, results in acute lung inflammation and the subsequent development of chronic fibrosis, suggesting a potential human health risk to individuals involved in the manufacturing of products utilizing these nanomaterials. Induction of IL-1beta secretion via activation of the inflammasome is a prime mechanism of MWCNT-induced inflammation. The inflammasome is a multi-protein scaffold found in a variety of cell types that forms in response to a variety of immune signals, including particulates. Sensitization with allergens, such as house dust mite (HDM), increases levels of the T helper 2 (Th2) cytokines IL-4 and IL-13 in mice and in humans, and there is particular cause for concern in cases of MWCNT exposure in individuals with pre-existing allergic airway disease, such as asthma. MWCNT exposure exacerbates airway inflammation and fibrosis in animal models of pre-existing allergic asthma, suggesting that individuals suffering from asthma are more susceptible to the toxic pulmonary effects of MWCNT exposure. Asthma is an exceptionally prominent human disease, and therefore the goal of this research was to better understand how pre-existing allergic airway

  19. Dual oxidase regulates neutrophil recruitment in allergic airways.

    PubMed

    Chang, Sandra; Linderholm, Angela; Franzi, Lisa; Kenyon, Nicholas; Grasberger, Helmut; Harper, Richart

    2013-12-01

    Enhanced reactive oxygen species production in allergic airways is well described and correlates with increased airway contractions, inflammatory cell infiltration, goblet cell metaplasia, and mucus hypersecretion. There is also an abundance of interleukin-4/interleukin-13 (IL-4/IL-13)- or interleukin-5-secreting cells that are thought to be central to the pathogenesis of allergic asthma. We postulated that the dual oxidases (DUOX1 and DUOX2), members of the nicotinamide adenine dinucleotide phosphate oxidase family that release hydrogen peroxide (H2O2) in the respiratory tract, are critical proteins in the pathogenesis of allergic airways. DUOX activity is regulated by cytokines, including IL-4 and IL-13, and DUOX-mediated H2O2 influences several important features of allergic asthma: mucin production, IL-8 secretion, and wound healing. The objective of this study was to establish the contribution of DUOXs to the development of allergic asthma in a murine model. To accomplish this goal, we utilized a DUOXA-deficient mouse model (Duoxa(-/-)) that lacked maturation factors for both DUOX1 and DUOX2. Our results are the first to demonstrate evidence of DUOX protein and DUOX functional activity in murine airway epithelium. We also demonstrate that DUOXA maturation factors are required for airway-specific H2O2 production and localization of DUOX to cilia of fully differentiated airway epithelial cells. We compared wild-type and Duoxa(-/-) mice in an ovalbumin exposure model to determine the role of DUOX in allergic asthma. In comparison to DUOX-intact mice, Duoxa(-/-) mice had reduced mucous cell metaplasia and lower levels of TH2 cytokine levels in bronchoalveolar fluid. In addition, increased airway resistance in response to methacholine was observed in Duoxa(+/+) mice, as expected, but was absent in Duoxa(-/-) mice. Surprisingly, Duoxa(-/-) mice had decreased influx of neutrophils in bronchoalveolar fluid and lung tissue sections associated with a lower level of the

  20. Allergic sensitization: screening methods

    PubMed Central

    2014-01-01

    Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute. PMID:24739743

  1. Effects of local nasal immunotherapy in allergic airway inflammation: Using urea denatured Dermatophagoides pteronyssinus.

    PubMed

    Yu, Sheng-Jie; Liao, En-Chih; Tsai, Jaw-Ji

    2015-01-01

    Despite improvements in anti-allergy medication, the prevalence of allergic airway inflammation remains high, affecting up to 40% of the population worldwide. Allergen immunotherapy is effective for inducing tolerance but has the adverse effect of severe allergic reaction. This can be avoided by denaturing with urea. In this study, we demonstrated that the serum level of allergen-specific IgE in mice sensitized with native Dermatophagoides pteronyssinus (Der p) crude extract after receiving local nasal immunotherapy (LNIT) with urea-denatured Der p crude extract (DN-Dp) significantly decreased compared to that in the normal saline (NS) treatment group. Expressions of IL-4 were significantly reduced in lung tissues after treatment. Inflammation around the bronchial epithelium improved and airway hypersensitivity was down-regulated. LNIT with DN-Dp can down-regulate IL-1b, IL-6 and TNF-a expression and then decrease Der p-induced allergic airway inflammation. This therapeutic modality may be used as an alternative treatment for airway allergic diseases.

  2. HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation

    PubMed Central

    2012-01-01

    Background The pathogenesis of allergic airway inflammation in asthmatic patients is complex and characterized by cellular infiltrates and activity of many cytokines and chemokines. Both the transcription factor hypoxia inducible factor-1 (HIF-1) and chemokine CCL2 have been shown to play pivotal roles in allergic airway inflammation. The interrelationship between these two factors is not known. We hypothesized that the expression of HIF-1 and CCL2 may be correlated and that the expression of CCL2 may be under the regulation of HIF-1. Several lines of evidence are presented to support this hypothesis. Methods The effects of treating wild-type OVA (ovalbumin)-sensitized/challenged mice with ethyl-3,4-dihydroxybenzoate (EDHB), which upregulate HIF, on CCL2 expression, were determined. Mice conditionally knocked out for HIF-1β was examined for their ability to mount an allergic inflammatory response and CCL2 expression in the lung after intratracheal exposure to ovalbumin. The association of HIF-1α and CCL2 levels was also measured in endobronchial biopsies and bronchial fluid of asthma patients after challenge. Results We show that both HIF-1α and CCL2 were upregulated during an OVA (ovalbumin)-induced allergic response in mice. The levels of HIF-1α and CCL2 were significantly increased following treatment with a pharmacological agent which upregulates HIF-1α, ethyl-3,4-dihydroxybenzoate (EDHB). In contrast, the expression levels of HIF-1α and CCL2 were decreased in the lungs of mice that have been conditionally knocked out for ARNT (HIF-1β) following sensitization with OVA when compared to levels in wild type mice. In asthma patients, the levels of HIF-1α and CCL2 increased after challenge with the allergen. Conclusions These data suggest that CCL2 expression is regulated, in part, by HIF-1 in the lung. These findings also demonstrate that both CCL2 and HIF-1 are implicated in the pathogenesis of allergic airway inflammation. PMID:22823210

  3. Role of sensitization to mammalian serum albumin in allergic disease.

    PubMed

    Liccardi, Gennaro; Asero, Riccardo; D'Amato, Maria; D'Amato, Gennaro

    2011-10-01

    Serum albumin (SA) constitutes an intriguing puzzle that is involved in allergic sensitizations from different sources and induces different clinical manifestations. In this article, we describe the role of sensitization to SAs in inducing allergic diseases and the complex interactions and cross-reactivity between SA resulting from its presence in various mammalian tissues and fluids. SAs alone are an uncommon cause of allergic sensitization in airways, but these allergenic proteins likely play a significant role as cross-reacting allergens in individuals sensitized to several types of animal dander. SAs are a minor allergen in milk but a major allergen in meats. Recently, bovine SA has been added to the culture medium of spermatozoids used for artificial insemination. As a consequence, some case reports have shown that bovine SA may be a causative agent in severe anaphylaxis after standard intrauterine insemination or in vitro fertilization. PMID:21809117

  4. Role of sensitization to mammalian serum albumin in allergic disease.

    PubMed

    Liccardi, Gennaro; Asero, Riccardo; D'Amato, Maria; D'Amato, Gennaro

    2011-10-01

    Serum albumin (SA) constitutes an intriguing puzzle that is involved in allergic sensitizations from different sources and induces different clinical manifestations. In this article, we describe the role of sensitization to SAs in inducing allergic diseases and the complex interactions and cross-reactivity between SA resulting from its presence in various mammalian tissues and fluids. SAs alone are an uncommon cause of allergic sensitization in airways, but these allergenic proteins likely play a significant role as cross-reacting allergens in individuals sensitized to several types of animal dander. SAs are a minor allergen in milk but a major allergen in meats. Recently, bovine SA has been added to the culture medium of spermatozoids used for artificial insemination. As a consequence, some case reports have shown that bovine SA may be a causative agent in severe anaphylaxis after standard intrauterine insemination or in vitro fertilization.

  5. Volatile Organic Compounds Enhance Allergic Airway Inflammation in an Experimental Mouse Model

    PubMed Central

    Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

    2012-01-01

    Background Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. Methods To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Results Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Conclusions Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases. PMID:22802943

  6. Impact of Adiponectin Overexpression on Allergic Airways Responses in Mice

    PubMed Central

    Verbout, Norah G.; Williams, Alison S.; Kasahara, David I.; Wurmbrand, Allison P.; Halayko, Andrew J.; Shore, Stephanie A.

    2013-01-01

    Obesity is an important risk factor for asthma. Obese individuals have decreased circulating adiponectin, an adipose-derived hormone with anti-inflammatory properties. We hypothesized that transgenic overexpression of adiponectin would attenuate allergic airways inflammation and mucous hyperplasia in mice. To test this hypothesis, we used mice overexpressing adiponectin (Adipo Tg). Adipo Tg mice had marked increases in both serum adiponectin and bronchoalveolar lavage (BAL) fluid adiponectin. Both acute and chronic ovalbumin (OVA) sensitization and challenge protocols were used. In both protocols, OVA-induced increases in total BAL cells were attenuated in Adipo Tg versus WT mice. In the acute protocol, OVA-induced increases in several IL-13 dependent genes were attenuated in Adipo Tg versus WT mice, even though IL-13 per se was not affected. With chronic exposure, though OVA-induced increases in goblet cells numbers per millimeter of basement membrane were greater in Adipo Tg versus WT mice, mRNA abundance of mucous genes in lungs was not different. Also, adiponectin overexpression did not induce M2 polarization in alveolar macrophages. Our results indicate that adiponectin protects against allergen-induced inflammatory cell recruitment to the airspaces, but not development of goblet cell hyperplasia. PMID:23861690

  7. Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy.

    PubMed

    Datta, Ankur; Moitra, Saibal; Hazra, Iman; Mondal, Somnath; Das, Prasanta Kumar; Singh, Manoj Kumar; Chaudhuri, Suhnrita; Bhattacharya, Debanjan; Tripathi, Santanu Kumar; Chaudhuri, Swapna

    2016-01-01

    Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcɛRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcɛRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities.

  8. Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy.

    PubMed

    Datta, Ankur; Moitra, Saibal; Hazra, Iman; Mondal, Somnath; Das, Prasanta Kumar; Singh, Manoj Kumar; Chaudhuri, Suhnrita; Bhattacharya, Debanjan; Tripathi, Santanu Kumar; Chaudhuri, Swapna

    2016-01-01

    Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcɛRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcɛRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities. PMID:26667977

  9. The spectrum of allergic fungal diseases of the upper and lower airways.

    PubMed

    Rodrigues, Jonathan; Caruthers, Carrie; Azmeh, Roua; Dykewicz, Mark S; Slavin, Raymond G; Knutsen, Alan P

    2016-01-01

    Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease. PMID:26776889

  10. Temporal Changes in Glutaredoxin 1 and Protein S-Glutathionylation in Allergic Airway Inflammation

    PubMed Central

    Maki, Kanako; Nagai, Katsura; Suzuki, Masaru; Inomata, Takashi; Yoshida, Takayuki; Nishimura, Masaharu

    2015-01-01

    Introduction Asthma is a chronic inflammatory disorder of the airways, involving oxidative stress. Upon oxidative stress, glutathione covalently binds to protein thiols to protect them against irreversible oxidation. This posttranslational modification, known as protein S-glutathionylation, can be reversed by glutaredoxin 1 (Glrx1) under physiological condition. Glrx1 is known to increase in the lung tissues of a murine model of allergic airway inflammation. However, the temporal relationship between levels of Glrx1, protein S-glutathionylation, and glutathione in the lungs with allergic airway inflammation is not clearly understood. Methods BALB/c mice received 3 aerosol challenges with ovalbumin (OVA) following sensitization to OVA. They were sacrificed at 6, 24, 48, or 72 h, or 8 days (5 mice per group), and the levels of Glrx1, protein S-glutathionylation, glutathione, and 25 cytokines/chemokines were evaluated in bronchoalveolar lavage fluid (BALF) and/or lung tissue. Results Levels of Glrx1 in BALF were significantly elevated in the OVA 6 h (final challenge) group compared to those in the control, with concurrent increases in protein S-glutathionylation levels in the lungs, as well as total glutathione (reduced and oxidized) and oxidized glutathione in BALF. Protein S-glutathionylation levels were attenuated at 24 h, with significant increases in Glrx1 levels in lung tissues at 48 and 72 h. Glrx1 in alveolar macrophages was induced after 6 h. Glrx1 levels concomitantly increased with Th2/NF-κB-related cytokines and chemokines in BALF. Conclusions The temporal relationships of Glrx1 with protein S-glutathionylation, glutathione, and cytokines/chemokines were observed as dynamic changes in lungs with allergic airway inflammation, suggesting that Glrx1 and protein–SSG redox status may play important roles in the development of allergic airway inflammation. PMID:25874776

  11. Diagnostic significance of nitric oxide concentrations in exhaled air from the airways in allergic rhinitis patients

    PubMed Central

    Krzych-Fałta, Edyta; Samoliński, Bolesław K; Zalewska, Marta

    2016-01-01

    Introduction The effect of nitric oxide (NO) on the human body is very important due its physiological regulation of the following functions of airways: modulation of ciliary movement and maintenance of sterility in sinuses. Aim To evaluate the diagnostic significance of NO concentrations in exhaled air from the upper and lower airways in patients diagnosed with allergic rhinitis (AR). Material and methods The subjects included in the study were a group of 30 people diagnosed with sensitivity to environmental allergens and a control group consisting of 30 healthy subjects. The measurement of NO in the air exhaled from the lower and upper airways was performed using an on-line method by means of Restricted Exhaled Breath (REB), as well as using the measurement procedure (chemiluminescence) set out in the guidelines prepared in 2005 by the American Thoracic Society and the European Respiratory Society. Results In the late phase of the allergic reaction, higher values of the level of exhaled NO concentration from the lower airways were observed in the groups of subjects up to the threshold values of 25.17 ppb in the group of subjects with year-round allergic rhinitis and 21.78 ppb in the group with diagnosed seasonal allergic rhinitis. The difference in the concentration of NO exhaled from the lungs between the test group and the control group in the 4th h of the test was statistically significant (p = 0.045). Conclusions Exhaled NO should be considered as a marker of airway inflammation. It plays an important role in the differential diagnosis of allergy. PMID:27279816

  12. Inhaled multiwalled carbon nanotubes potentiate airway fibrosis in murine allergic asthma.

    PubMed

    Ryman-Rasmussen, Jessica P; Tewksbury, Earl W; Moss, Owen R; Cesta, Mark F; Wong, Brian A; Bonner, James C

    2009-03-01

    Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m(3)) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-beta1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-beta1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-beta1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.

  13. Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma

    PubMed Central

    Ryman-Rasmussen, Jessica P.; Tewksbury, Earl W.; Moss, Owen R.; Cesta, Mark F.; Wong, Brian A.; Bonner, James C.

    2009-01-01

    Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT. PMID:18787175

  14. Inhibition of pan neurotrophin receptor p75 attenuates diesel particulate-induced enhancement of allergic airway responses in C57/B16J mice.

    PubMed

    Farraj, Aimen K; Haykal-Coates, Najwa; Ledbetter, Allen D; Evansky, Paul A; Gavett, Stephen H

    2006-06-01

    Recent investigations have linked neurotrophins, including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF), to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle (DEP) exposure has been linked to asthma exacerbation in many cities with vehicular traffic congestion. We tested the hypothesis that DEP-induced enhancement of the hallmark features of allergic airway disease in a murine model is dependent on the function of the pan neurotrophin receptor p75. Ovalbumin (OVA)-sensitized C57B1/6J mice were intranasally instilled with an antibody against the p75 receptor or saline alone 1 h before OVA challenge. The mice were then exposed nose-only to the PM2.5 fraction of SRM2975 DEP or air alone for 5 h beginning 1 h after OVA challenge. Two days later, air-exposed OVA-allergic mice developed a small but insignificant increase in methacholine-induced airflow obstruction relative to air-exposed, vehicle-sensitized mice. DEP-exposed OVA-allergic mice had a significantly greater degree of airway obstruction than all other groups. Instillation of anti-p75 significantly attenuated the DEP-induced increase in airway obstruction in OVA-allergic mice to levels similar to non-sensitized mice. The DEP-induced exacerbation of allergic airway responses may, in part, be mediated by neurotrophins.

  15. Adam8 Limits the Development of Allergic Airway Inflammation in Mice

    PubMed Central

    Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

    2013-01-01

    To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

  16. Protective effect of soybean oil- or fish oil-rich diets on allergic airway inflammation

    PubMed Central

    Navarro-Xavier, Roberta Araujo; de Barros, Karina Vieira; de Andrade, Iracema Senna; Palomino, Zaira; Casarini, Dulce Elena; Flor Silveira, Vera Lucia

    2016-01-01

    Background The increased prevalence of asthma and allergic diseases in westernized societies has been associated with increased intake of diets rich in n-6 fatty acids (FAs) and poor in n-3 FAs. This study aimed to analyze the prophylactic effects of treatment with a soybean oil-rich diet (rich in n-6) or fish oil (rich in n-3) in an allergic airway inflammation model on lung inflammation score, leukocyte migration, T-helper cell (Th)-2 (interleukin [IL]-4, IL-5) and Th1 (interferon [IFN]-γ, tumor necrosis factor-α) cytokines, lipoxin A4, nitric oxide, bradykinin, and corticosterone levels in bronchoalveolar lavage (BAL) or lungs. Methods Male Wistar rats fed with soybean oil- or fish oil-rich diet or standard rat chow were sensitized twice with ovalbumin–alumen and challenged twice with ovalbumin aerosol. The BAL and lungs were examined 24 hours later. Results Both diets, rich in n-6 or n-3 FAs, impaired the allergic lung inflammation and reduced leukocyte migration, eosinophil and neutrophil percentages, and IL-4/IL-5/bradykinin levels in BAL and/or lungs, as well as increased the nitric oxide levels in BAL. The soybean oil-rich diet additionally increased the levels of lipoxin A4 and corticosterone in the lungs. Conclusion Data presented demonstrated that the n-6 FA-rich diet had protective effect upon allergic airway inflammation and was as anti-inflammatory as the n-3 FA-rich diet, although through different mechanisms, suggesting that both diets could be considered as complementary therapy or a prophylactic alternative for allergic airway inflammation. PMID:27274303

  17. Toxoplasma gondii infection induces suppression in a mouse model of allergic airway inflammation.

    PubMed

    Fenoy, Ignacio M; Chiurazzi, Romina; Sánchez, Vanesa R; Argenziano, Mariana A; Soto, Ariadna; Picchio, Mariano S; Martin, Valentina; Goldman, Alejandra

    2012-01-01

    Allergic asthma is an inflammatory disorder characterized by infiltration of the airway wall with inflammatory cells driven mostly by activation of Th2-lymphocytes, eosinophils and mast cells. There is a link between increased allergy and a reduction of some infections in Western countries. Epidemiological data also show that respiratory allergy is less frequent in people exposed to orofecal and foodborne microbes such as Toxoplasma gondii. We previously showed that both acute and chronic parasite T. gondii infection substantially blocked development of airway inflammation in adult BALB/c mice. Based on the high levels of IFN-γ along with the reduction of Th2 phenotype, we hypothesized that the protective effect might be related to the strong Th1 immune response elicited against the parasite. However, other mechanisms could also be implicated. The possibility that regulatory T cells inhibit allergic diseases has received growing support from both animal and human studies. Here we investigated the cellular mechanisms involved in T. gondii induced protection against allergy. Our results show for the first time that thoracic lymph node cells from mice sensitized during chronic T. gondii infection have suppressor activity. Suppression was detected both in vitro, on allergen specific T cell proliferation and in vivo, on allergic lung inflammation after adoptive transference from infected/sensitized mice to previously sensitized animals. This ability was found to be contact-independent and correlated with high levels of TGF-β and CD4(+)FoxP3(+) cells. PMID:22952678

  18. Neonatal Streptococcus pneumoniae Infection May Aggravate Adulthood Allergic Airways Disease in Association with IL-17A

    PubMed Central

    Yang, Ting; Jiang, Xiaoli; Zhang, Liqun; Wang, Lijia; Wang, Qinghong; Luo, Zhengxiu; Liu, Enmei; Fu, Zhou

    2015-01-01

    Epidemiologic studies have demonstrated that some bacteria colonization or infections in early-life increased the risk for subsequent asthma development. However, little is known about the mechanisms by which early-life bacterial infection increases this risk. The aim of this study was to investigate the effect of neonatal Streptococcus pneumoniae infection on the development of adulthood asthma, and to explore the possible mechanism. A non-lethal S. pneumoniae lung infection was established by intranasal inoculation of neonatal (1-week-old) female mice with D39. Mice were sensitized and challenged with ovalbumin in adulthood to induce allergic airways disease (AAD). Twenty-four hours later, the lungs and bronchoalveolar lavage fluid (BALF) were collected to assess AAD. Neonatal S. pneumoniae infection exacerbated adulthood hallmark features of AAD, with enhanced airway hyperresponsiveness and increased neutrophil recruitment into the airways, increased Th17 cells and interleukin (IL)-17A productions. Depletion of IL-17A by i.p. injection of a neutralizing monoclonal antibody reduced neutrophil recruitment into the airways, alleviated airway inflammation and decreased airway hyperresponsiveness. Furthermore, IL-17A depletion partially restored levels of inteferon-γ, but had no effect on the release of IL-5 or IL-13. Our data suggest that neonatal S. pneumoniae infection may promote the development of adulthood asthma in association with increased IL-17A production. PMID:25816135

  19. Restoring airway epithelial barrier dysfunction: a new therapeutic challenge in allergic airway disease.

    PubMed

    Steelant, B; Seys, S F; Boeckxstaens, G; Akdis, C A; Ceuppens, J L; Hellings, P W

    2016-09-01

    An intact functional mucosal barrier is considered to be crucial for the maintenance of airway homeostasis as it protects the host immune system from exposure to allergens and noxious environmental triggers. Recent data provided evidence for the contribution of barrier dysfunction to the development of inflammatory diseases in the airways, skin and gut. A defective barrier has been documented in chronic rhinosinusitis, allergic rhinitis, asthma, atopic dermatitis and inflammatory bowel diseases. However, it remains to be elucidated to what extent primary (genetic) versus secondary (inflammatory) mechanisms drive barrier dysfunction. The precise pathogenesis of barrier dysfunction in patients with chronic mucosal inflammation and its implications on tissue inflammation and systemic absorption of exogenous particles are only partly understood. Since epithelial barrier defects are linked with chronicity and severity of airway inflammation, restoring the barrier integrity may become a useful approach in the treatment of allergic diseases. We here provide a state-of-the-art review on epithelial barrier dysfunction in upper and lower airways as well as in the intestine and the skin and on how barrier dysfunction can be restored from a therapeutic perspective.

  20. Alveolar macrophages from allergic lungs are not committed to a pro-allergic response and can reduce airway hyperresponsiveness following ex vivo culture

    PubMed Central

    Pouliot, P.; Spahr, A.; Careau, É.; Turmel, V.; Bissonnette, E. Y.

    2016-01-01

    Summary Background We already demonstrated that adoptive transfer of alveolar macrophages (AMs) from non-allergic rats into AM-depleted allergic rats prevents airway hyperresponsiveness (AHR). We also showed that AMs from non-sensitized, but not from sensitized, allergy-prone rats can prevent AHR following allergen challenge in sensitized allergic animals, establishing the importance of rat immunological status on the modulation of AM functions and suggesting that an allergic lung environment alters AM functions. Objective We investigated how the activation of allergic AMs can be modulated to reinstitute them with their capacity to reduce AHR. Methods AMs from sensitized Brown Norway rats were cultured ex vivo for up to 18 h in culture media to deprogram them from the influence of the allergic lung before being reintroduced into the lung of AM-depleted sensitized recipient. AHR and cytokines in bronchoalveolar lavage (BAL) were measured following allergen challenge. AMs stimulated ex vivo with Bacillus Calmette-Guerin(BCG) were used as positive controls as BCG induces a T-helper type 1 activation in AMs. Results AMs ex vivo cultured for 4–18 h reduced AHR to normal level. Interestingly, pro-allergic functions of AMs were dampened by 18 h culture and they reduced AHR even after spending 48 h in an allergic lung microenvironment. Furthermore, transfer of cultured AMs caused an increase in the levels of IFN-γ and IL-12 in BAL when compared with their ovalbumin control. After 18 h of ex vivo culture, AMs expressed reduced levels of TNF, IL-1α, IL-6, and Arginase-2 mRNAs compared with freshly isolated AMs, suggesting that ex vivo culture exempted AMs from lung stimuli that affected their functions. Conclusions There is a significant crosstalk between lung microenvironment and AMs, affecting their functions. It is also the first report showing that sensitized AMs can be modulated ex vivo to reduce lung pro-allergic environment, opening the way to therapies targetting

  1. Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice

    PubMed Central

    Glaab, Thomas; Ziegert, Michaela; Baelder, Ralf; Korolewitz, Regina; Braun, Armin; Hohlfeld, Jens M; Mitzner, Wayne; Krug, Norbert; Hoymann, Heinz G

    2005-01-01

    Background This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice. Methods Using noninvasive head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50), we determined early AR (EAR) to inhaled Aspergillus fumigatus antigens in conscious mice. These measurements were paralleled by invasive determination of pulmonary conductance (GL), dynamic compliance (Cdyn) and EF50 in another group of anesthetized, orotracheally intubated mice. Results With both methods, allergic mice, sensitized and boosted with A. fumigatus, elicited allergen-specific EAR to A. fumigatus (p < 0.05 versus controls). Dose-response studies to aerosolized methacholine (MCh) were performed in the same animals 48 h later, showing that allergic mice relative to controls were distinctly more responsive (p < 0.05) and revealed acute airway inflammation as evidenced from increased eosinophils and lymphocytes in bronchoalveolar lavage. Conclusion We conclude that invasive and noninvasive pulmonary function tests are capable of detecting both allergen-specific and cholinergic AR in intact, allergic mice. The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF50 method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice. PMID:16309547

  2. Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function.

    PubMed

    Sussan, Thomas E; Gajghate, Sachin; Chatterjee, Samit; Mandke, Pooja; McCormick, Sarah; Sudini, Kuladeep; Kumar, Sarvesh; Breysse, Patrick N; Diette, Gregory B; Sidhaye, Venkataramana K; Biswal, Shyam

    2015-07-01

    Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility.

  3. Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization.

    PubMed

    Smarr, Charles B; Yap, Woon Teck; Neef, Tobias P; Pearson, Ryan M; Hunter, Zoe N; Ifergan, Igal; Getts, Daniel R; Bryce, Paul J; Shea, Lonnie D; Miller, Stephen D

    2016-05-01

    Specific immunotherapy (SIT) is the most widely used treatment for allergic diseases that directly targets the T helper 2 (Th2) bias underlying allergy. However, the most widespread clinical applications of SIT require a long period of dose escalation with soluble antigen (Ag) and carry a significant risk of adverse reactions, particularly in highly sensitized patients who stand to benefit most from a curative treatment. Thus, the development of safer, more efficient methods to induce Ag-specific immune tolerance is critical to advancing allergy treatment. We hypothesized that antigen-associated nanoparticles (Ag-NPs), which we have used to prevent and treat Th1/Th17-mediated autoimmune disease, would also be effective for the induction of tolerance in a murine model of Th2-mediated ovalbumin/alum-induced allergic airway inflammation. We demonstrate here that antigen-conjugated polystyrene (Ag-PS) NPs, although effective for the prophylactic induction of tolerance, induce anaphylaxis in presensitized mice. Antigen-conjugated NPs made of biodegradable poly(lactide-co-glycolide) (Ag-PLG) are similarly effective prophylactically, are well tolerated by sensitized animals, but only partially inhibit Th2 responses when administered therapeutically. PLG NPs containing encapsulated antigen [PLG(Ag)], however, were well tolerated and effectively inhibited Th2 responses and airway inflammation both prophylactically and therapeutically. Thus, we illustrate progression toward PLG(Ag) as a biodegradable Ag carrier platform for the safe and effective inhibition of allergic airway inflammation without the need for nonspecific immunosuppression in animals with established Th2 sensitization. PMID:27091976

  4. Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB.

    PubMed

    Goh, Fera Y; Upton, Nadine; Guan, Shouping; Cheng, Chang; Shanmugam, Muthu K; Sethi, Gautam; Leung, Bernard P; Wong, W S Fred

    2012-03-15

    Persistent activation of nuclear factor-κB (NF-κB) has been associated with the development of asthma. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring bioactive flavonol, has been shown to inhibit NF-κB activity. We hypothesized that fisetin may attenuate allergic asthma via negative regulation of the NF-κB activity. Female BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Fisetin dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of adhesion molecules, chitinase, IL-17, IL-33, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. Fisetin blocked NF-κB subunit p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. In normal human bronchial epithelial cells, fisetin repressed TNF-α-induced NF-κB-dependent reporter gene expression. Our findings implicate a potential therapeutic value of fisetin in the treatment of asthma through negative regulation of NF-κB pathway.

  5. Toxoplasma gondii infection blocks the development of allergic airway inflammation in BALB/c mice.

    PubMed

    Fenoy, I; Giovannoni, M; Batalla, E; Martin, V; Frank, F M; Piazzon, I; Goldman, A

    2009-02-01

    There is a link between increased allergy and a reduction of some infections in western countries. Epidemiological data also show that respiratory allergy is less frequent in people exposed to orofaecal and foodborne microbes such as Toxoplasma gondii. Infection with T. gondii induces a strong cell-mediated immunity with a highly polarized T helper type 1 (Th1) response in early stages of infection. Using a well-known murine model of allergic lung inflammation, we sought to investigate whether T. gondii infection could modulate the susceptibility to develop respiratory allergies. Both acute and chronic infection with T. gondii before allergic sensitization resulted in a diminished allergic inflammation, as shown by a decrease in bronchoalveolar lavage (BAL) eosinophilia, mononuclear and eosinophil cell infiltration around airways and vessels and goblet cell hyperplasia. Low allergen-specific immunoglobulin (Ig)E and IgG1 and high levels of allergen-specific IgG2a serum antibodies were detected. A decreased interleukin (IL)-4 and IL-5 production by lymph node cells was observed, while no antigen-specific interferon-gamma increase was detected. Higher levels of the regulatory cytokine IL-10 were found in BAL from infected mice. These results show that both acute and chronic parasite infection substantially blocked development of airway inflammation in adult BALB/c mice. Our results support the hypothesis that T. gondii infection contributes to protection against allergy in humans. PMID:19032550

  6. Rapamycin attenuates airway hyperreactivity, goblet cells, and IgE in experimental allergic asthma.

    PubMed

    Mushaben, Elizabeth M; Kramer, Elizabeth L; Brandt, Eric B; Khurana Hershey, Gurjit K; Le Cras, Timothy D

    2011-12-01

    The mammalian target of rapamycin (mTOR) signaling pathway integrates environmental cues, promotes cell growth/differentiation, and regulates immune responses. Although inhibition of mTOR with rapamycin has potent immunosuppressive activity, mixed effects have been reported in OVA-induced models of allergic asthma. We investigated the impact of two rapamycin treatment protocols on the major characteristics of allergic asthma induced by the clinically relevant allergen, house dust mite (HDM). In protocol 1, BALB/c mice were exposed to 10 intranasal HDM doses over a period of 24 d and treated with rapamycin simultaneously during the sensitization/exposure period. In protocol 2, rapamycin was administered after the mice had been sensitized to HDM (i.p. injection) and prior to initiation of two intranasal HDM challenges over 4 d. Airway hyperreactivity (AHR), IgE, inflammatory cells, cytokines, leukotrienes, goblet cells, and activated T cells were assessed. In protocol 1, rapamycin blocked HDM-induced increases in AHR, inflammatory cell counts, and IgE, as well as attenuated goblet cell metaplasia. In protocol 2, rapamycin blocked increases in AHR, IgE, and T cell activation and reduced goblet cell metaplasia, but it had no effect on inflammatory cell counts. Increases in IL-13 and leukotrienes were also blocked by rapamycin, although increases in IL-4 were unaffected. These data demonstrated that rapamycin can inhibit cardinal features of allergic asthma, including increases in AHR, IgE, and goblet cells, most likely as a result of its ability to reduce the production of two key mediators of asthma: IL-13 and leukotrienes. These findings highlight the importance of the mTOR pathway in allergic airway disease. PMID:22021618

  7. Rapamycin attenuates airway hyperreactivity, goblet cells, and IgE in experimental allergic asthma.

    PubMed

    Mushaben, Elizabeth M; Kramer, Elizabeth L; Brandt, Eric B; Khurana Hershey, Gurjit K; Le Cras, Timothy D

    2011-12-01

    The mammalian target of rapamycin (mTOR) signaling pathway integrates environmental cues, promotes cell growth/differentiation, and regulates immune responses. Although inhibition of mTOR with rapamycin has potent immunosuppressive activity, mixed effects have been reported in OVA-induced models of allergic asthma. We investigated the impact of two rapamycin treatment protocols on the major characteristics of allergic asthma induced by the clinically relevant allergen, house dust mite (HDM). In protocol 1, BALB/c mice were exposed to 10 intranasal HDM doses over a period of 24 d and treated with rapamycin simultaneously during the sensitization/exposure period. In protocol 2, rapamycin was administered after the mice had been sensitized to HDM (i.p. injection) and prior to initiation of two intranasal HDM challenges over 4 d. Airway hyperreactivity (AHR), IgE, inflammatory cells, cytokines, leukotrienes, goblet cells, and activated T cells were assessed. In protocol 1, rapamycin blocked HDM-induced increases in AHR, inflammatory cell counts, and IgE, as well as attenuated goblet cell metaplasia. In protocol 2, rapamycin blocked increases in AHR, IgE, and T cell activation and reduced goblet cell metaplasia, but it had no effect on inflammatory cell counts. Increases in IL-13 and leukotrienes were also blocked by rapamycin, although increases in IL-4 were unaffected. These data demonstrated that rapamycin can inhibit cardinal features of allergic asthma, including increases in AHR, IgE, and goblet cells, most likely as a result of its ability to reduce the production of two key mediators of asthma: IL-13 and leukotrienes. These findings highlight the importance of the mTOR pathway in allergic airway disease.

  8. BLOCKADE OF TRKA OR P75 NEUROTROPHIN RECEPTORS ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAYS RESPONSES IN BALB/C MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway resistance. Exposure to diesel exhaust particles (DEP) associated with the combustion of diesel fuel exacerbates allergic airways responses. We tested t...

  9. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    SciTech Connect

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurélio; Silva Dias, Celidarque da; Piuvezam, Márcia Regina; and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  10. [Housing conditions and allergic sensitization in children].

    PubMed

    Heinrich, J; Hölscher, B; Wjst, M

    1998-09-01

    Genetic predisposition and indoor exposure to allergens-especially during the very early childhood years are major factors for the development of allergic diseases later in life. The present study analyzed the association between allergic sensitization in children aged 5 to 14 years and residing since birth in homes of different building types. A cross-sectional study of 811 children aged 5 to 14 years who resided in the same home since birth investigated indoor factors using a questionnaire and allergic sensitization assessed by skin prick test. The prevalence of allergic sensitization was compared between children who lived since birth in five different building types. After adjustment for age, gender, parental education and study area the odds of allergic sensitization were higher among children who lived in prefabricated concrete slab buildings built after 1970 (OR 1.56, 95% CI: 1.02-2.38) and among children who lived in new brick buildings (OR 1.75, 95% CI: 0.88-3.47) than among children who lived in old brick buildings. Moreover, the odds of pollen sensitization was higher among children who lived in the new building types (prefabricated slab buildings: OR 1.68, 95% CI: 1.04-2.72; new brick buildings: OR 1.48, 95% CI: 0.64-3.42) while living in timber-framed houses was associated with a higher odds of sensitization against mites (OR 1.63, 95% CI: 0.77-3.44). The step by step inclusion of single indoor factors like type of heating, numbers of building storeys, number of persons per room, environmental tobacco smoke, use of gas for cooking purposes, dampness of the home or visible moulds in the logistic regression model only marginally changed the odds ratios. Modern living conditions are associated with a higher odds of allergic sensitization. PMID:9789357

  11. The Role of Ion Channels to Regulate Airway Ciliary Beat Frequency During Allergic Inflammation.

    PubMed

    Joskova, M; Sutovska, M; Durdik, P; Koniar, D; Hargas, L; Banovcin, P; Hrianka, M; Khazaei, V; Pappova, L; Franova, S

    2016-01-01

    Overproduction of mucus is a hallmark of asthma. The aim of this study was to identify potentially effective therapies for removing excess mucus. The role of voltage-gated (Kir 6.1, KCa 1.1) and store-operated ion channels (SOC, CRAC) in respiratory cilia, relating to the tracheal ciliary beat frequency (CBF), was compared under the physiological and allergic airway conditions. Ex vivo experiments were designed to test the local effects of Kir 6.1, KCa 1.1 and CRAC ion channel modulators in a concentration-dependent manner on the CBF. Cilia, obtained with the brushing method, were monitored by a high-speed video camera and analyzed with ciliary analysis software. In natural conditions, a Kir 6.1 opener accelerated CBF, while CRAC blocker slowed it in a concentration-dependent manner. In allergic inflammation, the effect of Kir 6.1 opener was insignificant, with a tendency to decrease CBF. A cilio-inhibitory effect of a CRAC blocker, while gently reduced by allergic inflammation, remained significant. A KCa 1.1 opener turned out to significantly enhance the CBF under the allergic OVA-sensitized conditions. We conclude that optimally attuned concentration of KCa 1.1 openers or special types of bimodal SOC channel blockers, potentially given by inhalation, might benefit asthma. PMID:27369295

  12. Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice.

    PubMed Central

    Gavett, Stephen H; Haykal-Coates, Najwa; Copeland, Lisa B; Heinrich, Joachim; Gilmour, M Ian

    2003-01-01

    Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 micro m aerodynamic diameter; PM(2.5)) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM(2.5) from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM(2.5) from Hettstedt, but not PM(2.5) from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Hettstedt PM(2.5) whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only in allergic mice exposed to Hettstedt PM(2.5) before challenge. Both Hettstedt and Zerbst PM(2.5) significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM(2.5) influences the severity of allergic respiratory disease. PMID:12948886

  13. Effects of multi-walled carbon nanotubes on a murine allergic airway inflammation model

    SciTech Connect

    Inoue, Ken-ichiro Koike, Eiko; Yanagisawa, Rie; Hirano, Seishiro; Nishikawa, Masataka; Takano, Hirohisa

    2009-06-15

    The development of nanotechnology has increased the risk of exposure to types of particles other than combustion-derived particles in the environment, namely, industrial nanomaterials. On the other hand, patients with bronchial asthma are sensitive to inhaled substances including particulate matters. This study examined the effects of pulmonary exposure to a type of nano-sized carbon nanotube (multi-walled nanotubes: MWCNT) on allergic airway inflammation in vivo and their cellular mechanisms in vitro. In vivo, ICR mice were divided into 4 experimental groups. Vehicle, MWCNT (50 {mu}g/animal), ovalbumin (OVA), and OVA + MWCNT were repeatedly administered intratracheally. Bronchoalveolar lavage (BAL) cellularity, lung histology, levels of cytokines related to allergic inflammation in lung homogenates/BAL fluids (BALFs), and serum immunoglobulin levels were studied. Also, we evaluated the impact of MWCNT (0.1-1 {mu}g/ml) on the phenotype and function of bone marrow-derived dendritic cells (DC) in vitro. MWCNT aggravated allergen-induced airway inflammation characterized by the infiltration of eosinophils, neutrophils, and mononuclear cells in the lung, and an increase in the number of goblet cells in the bronchial epithelium. MWCNT with allergen amplified lung protein levels of Th cytokines and chemokines compared with allergen alone. MWCNT exhibited adjuvant activity for allergen-specific IgG{sub 1} and IgE. MWCNT significantly increased allergen (OVA)-specific syngeneic T-cell proliferation, particularly at a lower concentration in vitro. Taken together, MWCNT can exacerbate murine allergic airway inflammation, at least partly, via the promotion of a Th-dominant milieu. In addition, the exacerbation may be partly through the inappropriate activation of antigen-presenting cells including DC.

  14. Effect of P2X4R on airway inflammation and airway remodeling in allergic airway challenge in mice

    PubMed Central

    CHEN, HONGXIA; XIA, QINGQING; FENG, XIAOQIAN; CAO, FANGYUAN; YU, HANG; SONG, YINLI; NI, XIUQIN

    2016-01-01

    P2X4 receptor (P2X4R) is the most widely expressed subtype of the P2XRs in the purinergic receptor family. Adenosine triphosphate (ATP), a ligand for this receptor, has been implicated in the pathogenesis of asthma. ATP-P2X4R signaling is involved in pulmonary vascular remodeling, and in the proliferation and differentiation of airway and alveolar epithelial cell lines. However, the role of P2X4R in asthma remains to be elucidated. This aim of the present study was to investigate the effects of P2X4R in a murine experimental asthma model. The asthmatic model was established by the inhalation of ovalbumin (OVA) in BALB/c mice. The mice were treated with P2X4R-specific agonists and antagonists to investigate the role of this receptor in vivo. Pathological changes in the bronchi and lung tissues were examined using hematoxylin and eosin staining, Masson's trichrome staining and Alcian blue staining. The inflammatory cells in the bronchoalveolar lavage fluid were counted, and the expression levels of P2X4R, α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) were detected using western blotting. In the OVA-challenged mice, inflammation, infiltration, collagen deposition, mucus production, and the expression levels of P2X4R and PCNA were all increased; however, the expression of α-SMA was decreased, compared with the mice in the control group. Whereas treatment with the P2X4R agonist, ATP, enhanced the allergic reaction, treatment with the P2X4R antagonist, 5-BDBD, attenuated the allergic reaction. The results suggested that ATP-P2X4R signaling may not only contribute to airway inflammation, but it may also contribute to airway remodeling in allergic asthma in mice. PMID:26648454

  15. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

    PubMed Central

    Yarova, Polina L.; Stewart, Alecia L.; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A.; Lowe, Alexander P. P.; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C.; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J.; Ford, William R.; Broadley, Kenneth J.; Rietdorf, Katja; Chang, Wenhan; Khayat, Mohd E. Bin; Ward, Donald T.; Corrigan, Christopher J.; Ward, Jeremy P. T.; Kemp, Paul J.; Pabelick, Christina M.; Prakash, Y. S.; Riccardi, Daniela

    2016-01-01

    Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyper-reactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744

  16. Nerve growth factor and neurotrophin-3 mediate survival of pulmonary plasma cells during the allergic airway inflammation.

    PubMed

    Abram, Melanie; Wegmann, Michael; Fokuhl, Verena; Sonar, Sanchaita; Luger, Elke Olga; Kerzel, Sebastian; Radbruch, Andreas; Renz, Harald; Zemlin, Michael

    2009-04-15

    Allergen-specific Abs play a pivotal role in the induction and maintenance of allergic airway inflammation. During secondary immune responses, plasma cell survival and Ab production is mediated by extrinsic factors provided by the local environment (survival niches). It is unknown whether neurotrophins, a characteristic marker of allergic airway inflammation, influence plasma cell survival in the lung. Using a mouse model of allergic asthma, we found that plasma cells from the lung and spleen are distinct subpopulations exhibiting differential expression patterns of neurotrophins and their receptors (Trks). In vitro, the nerve growth factor (NGF) and neurotrophin-3 (NT3) led to a dose-dependent increase in viability of isolated pulmonary plasma cells due to up-regulation of the antiapoptotic Bcl2 pathway. In parallel, the expression of transcription factors that stimulate the production of immunoglobulins (X-box binding protein 1 and NF-kappaB subunit RelA) was enhanced in plasma cells treated with NGF and NT3. These findings were supported in vivo. When the NGF pathway was blocked by intranasal application of a selective TrkA inhibitor, sensitized mice showed reduced numbers of pulmonary plasma cells and developed lower levels of allergen-specific and total serum IgE in response to OVA inhalation. This suggests that in the allergic airway inflammation, NGF/TrkA-mediated pulmonary IgE production contributes significantly to serum-IgE levels. We conclude that the neurotrophins NGF and NT3 act as survival factors for pulmonary plasma cells and thus are important regulators of the local Ab production in the allergic airway disease.

  17. Nanoparticle uptake by airway phagocytes after fungal spore challenge in murine allergic asthma and chronic bronchitis

    PubMed Central

    2014-01-01

    Background In healthy lungs, deposited micrometer-sized particles are efficiently phagocytosed by macrophages present on airway surfaces; however, uptake of nanoparticles (NP) by macrophages appears less effective and is largely unstudied in lung disease. Using mouse models of allergic asthma and chronic obstructive pulmonary disease (COPD), we investigated NP uptake after challenge with common biogenic ambient air microparticles. Methods Bronchoalveolar lavage (BAL) cells from diseased mice (allergic asthma: ovalbumin [OVA] sensitized and COPD: Scnn1b-transgenic [Tg]) and their respective healthy controls were exposed ex vivo first to 3-μm fungal spores of Calvatia excipuliformis and then to 20-nm gold (Au) NP. Electron microscopic imaging was performed and NP uptake was assessed by quantitative morphometry. Results Macrophages from diseased mice were significantly larger compared to controls in OVA-allergic versus sham controls and in Scnn1b-Tg versus wild type (WT) mice. The percentage of macrophages containing AuNP tended to be lower in Scnn1b-Tg than in WT mice. In all animal groups, fungal spores were localized in macrophage phagosomes, the membrane tightly surrounding the spore, whilst AuNP were found in vesicles largely exceeding NP size, co-localized in spore phagosomes and occasionally, in the cytoplasm. AuNP in vesicles were located close to the membrane. In BAL from OVA-allergic mice, 13.9 ± 8.3% of all eosinophils contained AuNP in vesicles exceeding NP size and close to the membrane. Conclusions Overall, AuNP uptake by BAL macrophages occurred mainly by co-uptake together with other material, including micrometer-sized ambient air particles like fungal spores. The lower percentage of NP containing macrophages in BAL from Scnn1b-Tg mice points to a change in the macrophage population from a highly to a less phagocytic phenotype. This likely contributes to inefficient macrophage clearance of NP in lung disease. Finally, the AuNP containing

  18. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    PubMed Central

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma. PMID:27489884

  19. A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects.

    PubMed Central

    Calhoun, W J; Dick, E C; Schwartz, L B; Busse, W W

    1994-01-01

    Many patients with asthma have increased wheezing with colds. We hypothesized that rhinovirus colds might increase asthma by augmenting airway allergic responses (histamine release and eosinophil influx) after antigen challenge. Seven allergic rhinitis patients and five normal volunteers were infected with rhinovirus type 16 (RV16) and evaluated by segmental bronchoprovocation and bronchoalveolar lavage. Segmental challenge with saline and antigen was performed 1 mo before infection, during the acute infection, and 1 mo after infection. Lavage was performed immediately and 48 h after antigen challenge. Data were analyzed by two-way analysis of variance, and a P value of < or = 0.05 was considered to be significant. All volunteers inoculated with RV16 developed an acute respiratory infection. BAL fluid obtained from allergic rhinitis subjects during the acute viral infection, and 1 mo after infection, showed the following significant RV16-associated changes after antigen challenge: (a) an enhanced release of histamine immediately after local antigen challenge; (b) persistent histamine leak 48 h afterwards; and (c) a greater recruitment of eosinophils to the airway 48 h after challenge. These changes were not seen in non-allergic volunteers infected with RV16 and challenged with antigen, nor in allergic volunteers repetitively challenged with antigen but not infected with RV16, nor in RV16 infected allergic volunteers sham challenged with saline. We conclude that rhinovirus upper respiratory infection significantly augments immediate and late allergic responses in the airways of allergic individuals after local antigen challenge. These data suggest that one mechanism of increased asthma during a cold is an accentuation of allergic responses in the airway which may then contribute to bronchial inflammation. PMID:7989575

  20. INHIBITION OF PAN NEUROTROPHIN RECEPTOR P75 ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAY RESPONSES IN C57/BL6J MICE

    EPA Science Inventory

    Recent investigations have linked neurotrophins including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle...

  1. Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35.

    PubMed

    Moldaver, D M; Bharhani, M S; Wattie, J N; Ellis, R; Neighbour, H; Lloyd, C M; Inman, M D; Larché, M

    2014-03-01

    In the present study, we show therapeutic amelioration of established ovalbumin (OVA)-induced allergic airway disease following house dust mite (HDM) peptide therapy. Mice were sensitized and challenged with OVA and HDM protein extract (Dermatophagoides species) to induce dual allergen sensitization and allergic airway disease. Treatment of allergic mice with peptides derived from the major allergen Der p 1 suppressed OVA-induced airway hyperresponsiveness, tissue eosinophilia, and goblet cell hyperplasia upon rechallenge with allergen. Peptide treatment also suppressed OVA-specific T-cell proliferation. Resolution of airway pathophysiology was associated with a reduction in recruitment, proliferation, and effector function of T(H)2 cells and decreased interleukin (IL)-17⁺ T cells. Furthermore, peptide immunotherapy induced the regulatory cytokine IL-10 and increased the proportion of Fox p3⁺ cells among those expressing IL-10. Tolerance to OVA was not associated with increased IL-35. In conclusion, our results provide in vivo evidence for the creation of a tolerogenic environment following HDM peptide immunotherapy, leading to the therapeutic amelioration of established OVA-induced allergic airway disease.

  2. Alterations of the Lung Methylome in Allergic Airway Hyper-Responsiveness

    PubMed Central

    Cheng, Robert YS; Shang, Yan; Limjunyawong, Nathachit; Dao, Tyna; Das, Sandhya; Rabold, Richard; Sham, James SK; Mitzner, Wayne; Tang, Wan-Yee

    2014-01-01

    Asthma is a chronic airway disorder characterized by recurrent attacks of breathlessness and wheezing, affecting 300 million people around the world (available at: www.who.int). To date, genetic factors associated with asthma susceptibility have been unable to explain the full etiology of asthma. Recent studies have demonstrated that the epigenetic disruption of gene expression plays an equally important role in the development of asthma through interaction with our environment. We sensitized 6-week-old C57BL/6J mice with house-dust-mite (HDM) extracts intraperitoneally followed by 5 weeks of exposure to HDM challenges (three times a week) intratracheally. HDM-exposed mice showed an increase in airway hyper-responsiveness (AHR) and inflammation together with structural remodeling of the airways. We applied methylated DNA immunoprecipitation-next generation sequencing (MeDIP-seq) for profiling of DNA methylation changes in the lungs in response to HDM. We observed about 20 million reads by a single-run of massive parallel sequencing. We performed bioinformatics and pathway analysis on the raw sequencing data to identify differentially methylated candidate genes in HDM-exposed mice. Specifically, we have revealed that the transforming growth factor beta signaling pathway is epigenetically modulated by chronic exposure to HDM. Here, we demonstrated that a specific allergen may play a role in AHR through an epigenetic mechanism by disrupting the expression of genes in lungs that might be involved in airway inflammation and remodeling. Our findings provide new insights into the potential mechanisms by which environmental allergens induce allergic asthma and such insights may assist in the development of novel preventive and therapeutic options for this debilitative disease. PMID:24446183

  3. Allergic sensitization: host-immune factors

    PubMed Central

    2014-01-01

    Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased permeability of the epithelium, which is more susceptible to environmental triggers. Allergens and co-factors from the environment interact with innate immune receptors, such as Toll-like and protease-activated receptors on epithelial cells, stimulating them to produce cytokines that drive T-helper 2-like adaptive immunity in allergy-prone individuals. In this milieu, the next cells interacting with allergens are the dendritic cells lying just underneath the epithelium: plasmacytoid DCs, two types of conventional DCs (CD11b + and CD11b-), and monocyte-derived DCs. It is now becoming clear that CD11b+, cDCs, and moDCs are the inflammatory DCs that instruct naïve T cells to become Th2 cells. The simple paradigm of non-overlapping stable Th1 and Th2 subsets of T-helper cells is now rapidly being replaced by that of a more complex spectrum of different Th cells that together drive or control different aspects of allergic inflammation and display more plasticity in their cytokine profiles. At present, these include Th9, Th17, Th22, and Treg, in addition to Th1 and Th2. The spectrum of co-stimulatory signals coming from DCs determines which subset-characteristics will dominate. When IL-4 and/or IL-13 play a dominant role, B cells switch to IgE-production, a process that is more effective at young age. IgE-producing plasma cells have been shown to be long-lived, hiding in the bone-marrow or inflammatory tissues where they cannot easily be targeted by therapeutic intervention. Allergic sensitization is a complex interplay between the allergen in its environmental context and the tendency of the host’s innate and adaptive immune cells to be skewed towards allergic inflammation

  4. DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

    PubMed Central

    Habibovic, Aida; Hristova, Milena; Heppner, David E.; Danyal, Karamatullah; Ather, Jennifer L.; Janssen-Heininger, Yvonne M.W.; Irvin, Charles G.; Poynter, Matthew E.; Lundblad, Lennart K.; Dixon, Anne E.; Geiszt, Miklos

    2016-01-01

    Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite–induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1). DUOX1 deficiency also attenuated several EGFR-dependent features of HDM-induced allergic airway inflammation, including neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), mucous metaplasia, subepithelial fibrosis, and central airway resistance. Moreover, targeted inhibition of airway DUOX1 in mice with previously established HDM-induced allergic inflammation, by intratracheal administration of DUOX1-targeted siRNA or pharmacological NADPH oxidase inhibitors, reversed most of these outcomes. Our findings indicate an important function for DUOX1 in allergic inflammation related to persistent EGFR activation and suggest that DUOX1 targeting may represent an attractive strategy in asthma management. PMID:27812543

  5. Role of selective blocking of bradykinin receptor subtypes in attenuating allergic airway inflammation in guinea pigs.

    PubMed

    El-Kady, Mohamed M; Girgis, Zarif I; Abd El-Rasheed, Eman A; Shaker, Olfat; Attallah, Magdy I; Soliman, Ahmed A

    2016-10-01

    The present study was designed to evaluate the potential role of bradykinin antagonists (R-715; bradykinin B1 receptor antagonist and icatibant; bradykinin B2 receptor antagonist) in treatment of allergic airway inflammation in comparison to dexamethasone and montelukast. R-715 as dexamethasone significantly decreased peribronchial leukocyte infiltration, bronchoalveolar lavage fluid (BALF) albumin and interleukin 1β as well as serum OVA-specific IgE level. Also, R-715 like montelukast significantly decreased BALF cell count (total and eosinophils). Icatibant showed negative results. The current findings suggest that selective bradykinin B1 receptor antagonists may have the therapeutic potential for the treatment of allergic airway inflammation. PMID:27321873

  6. Characterization of NLRP12 during the Development of Allergic Airway Disease in Mice

    PubMed Central

    Allen, Irving C.; Lich, John D.; Arthur, Janelle C.; Jania, Corey M.; Roberts, Reid A.; Callaway, Justin B.; Tilley, Stephen L.; Ting, Jenny P.-Y.

    2012-01-01

    Among the 22 members of the nucleotide binding-domain, leucine rich repeat-containing (NLR) family, less than half have been functionally characterized. Of those that have been well studied, most form caspase-1 activating inflammasomes. NLRP12 is a unique NLR that has been shown to attenuate inflammatory pathways in biochemical assays and mediate the lymph node homing of activated skin dendritic cells in contact hypersensitivity responses. Since the mechanism between these two important observations remains elusive, we further evaluated the contribution of NLRP12 to organ specific adaptive immune responses by focusing on the lung, which, like skin, is exposed to both exogenous and endogenous inflammatory agents. In models of allergic airway inflammation induced by either acute ovalbumin (OVA) exposure or chronic house dust mite (HDM) antigen exposure, Nlrp12−/− mice displayed subtle differences in eosinophil and monocyte infiltration into the airways. However, the overall development of allergic airway disease and airway function was not significantly altered by NLRP12 deficiency. Together, the combined data suggest that NLRP12 does not play a vital role in regulating Th2 driven airway inflammation using common model systems that are physiologically relevant to human disease. Thus, the allergic airway inflammation models described here should be appropriate for subsequent studies that seek to decipher the contribution of NLRP12 in mediating the host response to agents associated with asthma exacerbation. PMID:22291998

  7. Do lipids influence the allergic sensitization process?

    PubMed Central

    Bublin, Merima; Eiwegger, Thomas; Breiteneder, Heimo

    2014-01-01

    Allergic sensitization is a multifactorial process that is not only influenced by the allergen and its biological function per se but also by other small molecular compounds, such as lipids, that are directly bound as ligands by the allergen or are present in the allergen source. Several members of major allergen families bind lipid ligands through hydrophobic cavities or electrostatic or hydrophobic interactions. These allergens include certain seed storage proteins, Bet v 1–like and nonspecific lipid transfer proteins from pollens and fruits, certain inhalant allergens from house dust mites and cockroaches, and lipocalins. Lipids from the pollen coat and furry animals and the so-called pollen-associated lipid mediators are codelivered with the allergens and can modulate the immune responses of predisposed subjects by interacting with the innate immune system and invariant natural killer T cells. In addition, lipids originating from bacterial members of the pollen microbiome contribute to the outcome of the sensitization process. Dietary lipids act as adjuvants and might skew the immune response toward a TH2-dominated phenotype. In addition, the association with lipids protects food allergens from gastrointestinal degradation and facilitates their uptake by intestinal cells. These findings will have a major influence on how allergic sensitization will be viewed and studied in the future. PMID:24880633

  8. Targeted inhibition of KCa3.1 channel attenuates airway inflammation and remodeling in allergic asthma.

    PubMed

    Yu, Zhi-Hua; Xu, Jian-Rong; Wang, Yan-Xia; Xu, Guang-Ni; Xu, Zu-Peng; Yang, Kai; Wu, Da-Zheng; Cui, Yong-Yao; Chen, Hong-Zhuan

    2013-06-01

    KCa3.1 has been suggested to be involved in regulating cell activation, proliferation, and migration in multiple cell types, including airway inflammatory and structural cells. However, the contributions of KCa3.1 to airway inflammation and remodeling and subsequent airway hyperresponsiveness (AHR) in allergic asthma remain to be explored. The main purpose of this study was to elucidate the roles of KCa3.1 and the potential therapeutic value of KCa3.1 blockers in chronic allergic asthma. Using real-time PCR, Western blotting, or immunohistochemical analyses, we explored the precise role of KCa3.1 in the bronchi of allergic mice and asthmatic human bronchial smooth muscle cells (BSMCs). We found that KCa3.1 mRNA and protein expression were elevated in the bronchi of allergic mice, and double labeling revealed that up-regulation occurred primarily in airway smooth muscle cells. Triarylmethane (TRAM)-34, a KCa3.1 blocker, dose-dependently inhibited the generation and maintenance of the ovalbumin-induced airway inflammation associated with increased Th2-type cytokines and decreased Th1-type cytokine, as well as subepithelial extracellular matrix deposition, goblet-cell hyperplasia, and AHR in a murine model of asthma. Moreover, the pharmacological blockade and gene silencing of KCa3.1, which was evidently elevated after mitogen stimulation, suppressed asthmatic human BSMC proliferation and migration, and arrested the cell cycle at the G0/G1 phase. In addition, the KCa3.1 activator 1-ethylbenzimidazolinone-induced membrane hyperpolarization and intracellular calcium increase in asthmatic human BSMCs were attenuated by TRAM-34. We demonstrate for the first time an important role for KCa3.1 in the pathogenesis of airway inflammation and remodeling in allergic asthma, and we suggest that KCa3.1 blockers may represent a promising therapeutic strategy for asthma.

  9. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome.

    PubMed

    Eyring, Kenneth R; Pedersen, Brent S; Yang, Ivana V; Schwartz, David A

    2015-01-01

    Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease. PMID:26642056

  10. Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

    SciTech Connect

    Bernard, Alfred Nickmilder, Marc; Dumont, Xavier

    2015-07-15

    It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

  11. SYNTHETIC COPPER-CONTAINING PARTICLES ENHANCE ALLERGIC AIRWAY RESPONSES IN MICE

    EPA Science Inventory

    SYNTHETIC COPPER-CONTAINING PARTICLES ENHANCE ALLERGIC AIRWAY RESPONSES IN MICE. SH Gavett, MI Gilmour, and N Haykal-Coates. National Health and Environ Effects Research Lab, USEPA, Res Triangle Park, NC USA
    Respiratory morbidity and mortality associated with increases in ...

  12. FACTORS THAT INFLUENCE THE RELATIVE POTENCY OF DIESEL EXHAUST PARTICLES AS ADJUVANTS IN ALLERGIC AIRWAY DISEASE

    EPA Science Inventory

    Description: Studies have shown that diesel exhaust particles (DEP) worsen respiratory diseases including allergic asthma. The adjuvant effects of DEP in the airways have been widely reported; however, the precise determinants and mechanisms of these effects are ill-defined. S...

  13. Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

    PubMed Central

    Folestad, Erika; Rowley, Jessica E.; Noll, Elisa M.; Walker, Simone A.; Lloyd, Clare M.; Rankin, Sara M.; Pietras, Kristian; Eriksson, Ulf; Fuxe, Jonas

    2015-01-01

    Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma. PMID:25637607

  14. Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.

    PubMed

    Johnson, Jill R; Folestad, Erika; Rowley, Jessica E; Noll, Elisa M; Walker, Simone A; Lloyd, Clare M; Rankin, Sara M; Pietras, Kristian; Eriksson, Ulf; Fuxe, Jonas

    2015-04-01

    Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma. PMID:25637607

  15. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies

    PubMed Central

    2012-01-01

    Background Increases in ambient particulate matter of aerodynamic diameter of 2.5 μm (PM2.5) are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. Methods We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either concentrated air particles (CAPs) or filtered air for 8 h (7:00 AM - 3:00 PM). Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF) and lung lobes were collected and evaluated for airway inflammatory and mucus responses. Results Similar CAPs mass concentrations were generated in Detroit (542 μg/m3) and Grand Rapids (519 μg/m3). Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase), eosinophils (90%), and total protein (300%) compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. Conclusions Despite inhalation exposure to the same mass concentration of urban PM2.5, disparate health

  16. Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model

    PubMed Central

    Zhang, Zhiyu; Shi, Lei; Pang, Wenhui; Liu, Wenwen; Li, Jianfeng; Wang, Haibo; Shi, Guanggang

    2016-01-01

    Background Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). Objective We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. Methods The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. Results Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. Conclusion Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper

  17. Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

    SciTech Connect

    Larsen, Søren Thor Wolkoff, Peder Hammer, Maria Kofoed-Sørensen, Vivi Clausen, Per Axel Nielsen, Gunnar Damgård

    2013-05-01

    We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (< 10%) relative humidity, respectively for 48 h prior to a 60-min exposure to either 0.4, 1.8 or about 5 ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5 ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4 ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways. - Highlights: ► Role of air humidity and allergy on sensitivity to an airway irritant was studied. ► In the humid environment, allergy amplified the effects of formaldehyde. ► In the dry environment, allergy reduced the effect of formaldehyde. ► Neither allergy nor humidity changed the formaldehyde-induced nasal irritation.

  18. Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin-induced allergic airway inflammation

    PubMed Central

    Zhong, Wenwei; Su, Wen; Zhang, Yanjie; Liu, Qi; Wu, Jinhong; Di, Caixia; Zhang, Zili; Xia, Zhenwei

    2014-01-01

    Antigen-induced allergic airway inflammation is mediated by T helper type 2 (Th2) cells and their cytokines, but the mechanism that initiates the Th2 immunity is not fully understood. Recent studies show that basophils play important roles in initiating Th2 immunity in some inflammatory models. Here we explored the role of basophils in ovalbumin (OVA) -induced airway allergic inflammation in BALB/c mice. We found that OVA sensitization and challenge resulted in a significant increase in the amount of basophils in blood and lung, along with the up-regulation of activation marker of CD200R. However, depletion of basophils with MAR-1 or Ba103 antibody attenuated airway inflammation, represented by the significantly decreased amount of the Th2 subset in spleen and draining lymph nodes, interlukin-4 level in lung and OVA-special immunoglobulin E (sIgE) levels in serum. On the other hand, adoptive transfer of basophils from OVA-challenged lung tissue to naive BALB/c mice provoked the Th2 immune response. In addition, pulmonary basophils from OVA-challenged mice were able to uptake DQ-OVA and express MHC class II molecules and CD40 in vivo, as well as to release interleukin-4 following stimulation by IgE–antigen complexes and promote Th2 polarization in vitro. These findings demonstrate that basophils may participate in Th2 immune responses in antigen-induced allergic airway inflammation and that they do so through facilitating antigen presentation and providing interleukin-4. PMID:24383680

  19. Epicutaneous Allergic Sensitization by Cooperation between Allergen Protease Activity and Mechanical Skin Barrier Damage in Mice.

    PubMed

    Shimura, Sakiko; Takai, Toshiro; Iida, Hideo; Maruyama, Natsuko; Ochi, Hirono; Kamijo, Seiji; Nishioka, Izumi; Hara, Mutsuko; Matsuda, Akira; Saito, Hirohisa; Nakae, Susumu; Ogawa, Hideoki; Okumura, Ko; Ikeda, Shigaku

    2016-07-01

    Allergen sources such as mites, insects, fungi, and pollen contain proteases. Airway exposure to proteases induces allergic airway inflammation and IgE/IgG1 responses via IL-33-dependent mechanisms in mice. We examined the epicutaneous sensitization of mice to a model protease allergen, papain; the effects of tape stripping, which induces epidermal barrier dysfunction; and the atopic march upon a subsequent airway challenge. Papain painting on ear skin and tape stripping cooperatively promoted dermatitis, the skin gene expression of proinflammatory cytokines and growth factors, up-regulation of serum total IgE, and papain-specific IgE/IgG1 induction. Epicutaneous sensitization induced T helper (Th) 2 cells and Th17 differentiation in draining lymph nodes. Ovalbumin and protease inhibitor-treated papain induced no or weak responses, whereas the co-administration of ovalbumin and papain promoted ovalbumin-specific IgE/IgG1 induction. Wild-type and IL-33-deficient mice showed similar responses in the epicutaneous sensitization phase. The subsequent airway papain challenge induced airway eosinophilia and maintained high papain-specific IgE levels in an IL-33-dependent manner. These results suggest that allergen source-derived protease activity and mechanical barrier damage such as that caused by scratching cooperatively promote epicutaneous sensitization and skin inflammation and that IL-33 is dispensable for epicutaneous sensitization but is crucial in the atopic march upon a subsequent airway low-dose encounter with protease allergens. PMID:26987428

  20. Effects of provinol and its combinations with clinically used antiasthmatics on airway defense mechanisms in experimental allergic asthma.

    PubMed

    Kazimierová, I; Jošková, M; Pecháňová, O; Šutovská, M; Fraňová, S

    2015-01-01

    Our previous studies show that provinol, a polyphenolic compound, has anti-inflammatory activity during allergic inflammation. In the present study we investigated the effects of provinol and its combinations with clinically used antiasthmatics: budesonide or theophylline on airway defense mechanisms during experimental allergic asthma. Separate groups of guinea pigs were treated during the course of 21-day ovalbumin sensitization with provinol (20 mg/kg/day, p.o.), or budesonide (1 mM by inhalation), or theophylline (10 mg/kg/day, i.p.), and with a half-dose combination of provinol+budesonide or provinol+theophylline. Airways defense mechanisms: cough reflex and specific airway resistance (sRaw) were evaluated in vivo. Tracheal smooth muscle reactivity and mucociliary clearance were examined in vitro. The findings were that provinol caused significant decreases in sRaw and in tracheal smooth muscle contractility, a suppression of cough reflex, and positively modulated ciliary beat frequency. The bronchodilatory and antitussive effects of provinol were comparable with those of budesonide and theophylline. Provinol given as add-on treatment significantly potentiated the effects of budesonide or theophylline, although the doses of each were halved. We conclude that provinol not only has bronchodilatory and antitussive effects, but also potentiates similar effects exerted by budesonide and theophylline.

  1. The Effects of Proresolution of Ellagic Acid in an Experimental Model of Allergic Airway Inflammation

    PubMed Central

    de Freitas Alves, Claudiney; Angeli, Giovanna Natalia; Favarin, Daniely Cornélio; Lemos de Andrade, Edinéia; Lazo Chica, Javier Emilio; Faccioli, Lúcia Helena; Roberto da Silva, Paulo; de Paula Rogerio, Alexandre

    2013-01-01

    Asthma is a disease of airway inflammation characterized by airway hyperresponsiveness, eosinophilic inflammation, and hypersecretion of mucus. Ellagic acid, a compound derived from medicinal plants and fruits, has shown anti-inflammatory activity in several experimental disease models. We used the classical experimental model, in BALB/c mice, of sensibilization with ovalbumin to determine the effect of ellagic acid (10 mg/kg; oral route) in the resolution of allergic airways response. Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control. The control group consisted of nonimmunized mice that received challenge with ovalbumin. Ellagic acid and dexamethasone or vehicle (water) were administered before or after intranasal allergen challenge. Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF), the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO) activity, and P-selectin expression, but not activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) pathways. In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways. Together, these findings identify ellagic acid as a potential therapeutic agent for accelerating the resolution of allergic airways inflammation. PMID:24376308

  2. Ovalbumin sensitization of guinea pig at birth prevents the ontogenetic decrease in airway smooth muscle responsiveness

    PubMed Central

    Chitano, Pasquale; Wang, Lu; Degan, Simone; Worthington, Charles L.; Pozzato, Valeria; Hussaini, Syed H.; Turner, Wesley C.; Dorscheid, Delbert R.; Murphy, Thomas M.

    2014-01-01

    Abstract Airway smooth muscle (ASM) displays a hyperresponsive phenotype at young age and becomes less responsive in adulthood. We hypothesized that allergic sensitization, which causes ASM hyperresponsiveness and typically occurs early in life, prevents the ontogenetic loss of the ASM hyperresponsive phenotype. We therefore studied whether neonatal allergic sensitization, not followed by later allergen challenges, alters the ontogenesis of ASM properties. We neonatally sensitized guinea pigs to ovalbumin and studied them at 1 week, 3 weeks, and 3 months (adult). A Schultz‐Dale response in isolated tracheal rings confirmed sensitization. The occurrence of inflammation was evaluated in the blood and in the submucosa of large airways. We assessed ASM function in tracheal strips as ability to produce force and shortening. ASM content of vimentin was also studied. A Schultz‐Dale response was observed in all 3‐week or older sensitized animals. A mild inflammatory process was characterized by eosinophilia in the blood and in the airway submucosa. Early life sensitization had no effect on ASM force generation, but prevented the ontogenetic decline of shortening velocity and the increase in resistance to shortening. Vimentin increased with age in control but not in sensitized animals. Allergic sensitization at birth without subsequent allergen exposures is sufficient to prevent normal ASM ontogenesis, inducing persistence to adulthood of an ASM hyperresponsive phenotype. PMID:25501429

  3. Effects of nitric acid on carbachol reactivity of the airways in normal and allergic sheep

    SciTech Connect

    Abraham, W.M.; Kim, C.S.; King, M.M.; Oliver, W. Jr.; Yerger, L.

    1982-01-01

    The airway effects of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance after carbachol inhalation were 68% (SD+/- 13%) and 82% (SD+/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post-exposure increases in specific pulmonary flow resistance for the normal and allergic sheep were 108% (SD+/- 51%(P<.06)) and 175% (SD+/- 87% (p<.02)), respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.

  4. Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation.

    PubMed

    Polte, Tobias; Petzold, Susanne; Bertrand, Jessica; Schütze, Nicole; Hinz, Denise; Simon, Jan C; Lehmann, Irina; Echtermeyer, Frank; Pap, Thomas; Averbeck, Marco

    2015-07-13

    Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.

  5. FeNO for detecting lower airway involvement in patients with allergic rhinitis

    PubMed Central

    Zhu, Zheng; Xie, Yanqing; Guan, Weijie; Gao, Yi; Xia, Shu; Zhong, Nanshan; Zheng, Jinping

    2016-01-01

    Allergic rhinitis (AR) is a risk factor for asthma development. The value of fractional exhaled nitric oxide (FeNO) in detecting lower airway involvement in the progress of AR-asthma march has not been evaluated. The aim of the present study was to investigate the value of FeNO in assessing lower airway inflammation and predicting bronchial hyperresponsiveness (BHR) in AR with or without asthma. FeNO and eosinophil count in induced sputum, and a methacholine bronchial provocation test were performed in 93 subjects, including: 45 AR patients (AR group); 20 patients with AR and asthma (AR with asthma group); and 28 normal controls (control group). The AR group was divided into two sub-groups: AR with asymptomatic BHR group and AR without BHR group. Correlation between FeNO and eosinophil count was assessed. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive and diagnostic value of FeNO in detecting BHR. The values of FeNO in the AR and AR with asthma groups were higher [29.5 (22.0) ppb and 61.5 (33.0) ppb] compared with the normal control group (16.0 (10.0) ppb), where the values in brackets indicate the interquartile range of the values. The percentages of eosinophils in induced sputum were 2.43±3.56, 7.36±4.98 and 18.58±11.26% in the control, AR and AR with asthma groups, respectively. For the diagnosis of BHR, the area under the curve (AUC) was 0.910 (95%CI 0.836, 0.984), with the sensitivity and specificity 0.846 and 0.817 when the cut-off value takes 31.5 ppb. For diagnosis of asthma, the AUC was 0.873 (95%CI 0.753, 0.992) with sensitivity 0.857 and specificity 0.847 when taking the cut-off value to be 38.0 ppb. The value of FeNO was well correlated with eosinophil count in the sputum. The measurement of FeNO is an effective method in detecting lower airway involvement in AR developing to asthma. PMID:27703499

  6. EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS

    EPA Science Inventory

    EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS (P. Singhl, D.W. Winsett2, M.J. Daniels2,
    C.A.J. Dick', K.B. Adlerl and M.I. Gilmour2, INCSU, Raleigh, N.C., 2NHEERL/ORD/ USEPA, RTP, N.C. and 3UNC, Chapel Hill, N.C.)The interaction between ...

  7. Phosphodiesterase 4B is essential for TH2-cell function and development of airway hyperresponsiveness in allergic asthma

    PubMed Central

    Catherine Jin, S.-L.; Goya, Sho; Nakae, Susumu; Wang, Dan; Bruss, Matthew; Hou, Chiaoyin; Umetsu, Dale; Conti, Marco

    2010-01-01

    Background Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined. Objectives We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and TH2-driven inflammatory responses. Methods Wild-type and PDE4B−/− mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and TH2 cytokine production were determined in cultured bronchial lymph node cells. Results Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased TH2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, TH2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the TH1 cytokine IFN-γ was not affected in PDE4B−/− mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation. Conclusion By relieving a cAMP-negative constraint, PDE4B plays an essential role in TH2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment. PMID:21047676

  8. Differences in airway reactivity in normal and allergic sheep after exposure to sulfur dioxide

    SciTech Connect

    Abraham, W.M.; Oliver, W. Jr.; Welker, M.J.; King, M.M.; Wanner, A.; Sackner, M.A.

    1981-12-01

    The effect of breathing 5 ppm sulfur dioxide (SO/sub 2/) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in which inhalation of Axcaris suum extract resulted in bronchospasm as evidenced by an increase in mean pulmonary flow resistance (RL), hyperinflation, and a fall in dynamic compliance. Airway reactivity was assessed by measuring the increase of RL after 18 breaths of 0.25% carbachol (c), from an initial RL value obtained after 18 breaths of buffered saline (s) (RL(c-s)). RL and RL(c-s) were determined prior to, immediately after, and 24 h after exposure to 5 ppm SO/sub 2/ for 4 h. In both groups RL remained unchanged after SO/sub 2/ exposure. Prior to exposure, RL(c-s) was not significantly different in seven normal (0.3 +/- 0.1) and seven allergic sheep (0.4 +/- 0.2 (SD) cmH/sub 2/O.l/sup -1/.s), and there was no significant change in RL (c-s) immediately after SO/sub 2/ exposure in either group. Twenty-four h later, RL(c-s) RL(c-s) increased to 0.7 +/- 0.8 (P < 0.2) in normal and to 1.8 +/- 0.9 cmH/sub 2/O.l/sup -1/.s (P < 0.01) in allergic sheep. Because the increase in RL(c-s) after 24 h was greater (P < 0.01) in allergic than in normal sheep, we conclude that SO/sub 2/ exposure increased airway reactivity more in the former than in the latter.

  9. Inhibition of acidic mammalian chitinase by RNA interference suppresses ovalbumin-sensitized allergic asthma.

    PubMed

    Yang, Ching-Jen; Liu, Yu-Kuo; Liu, Chao-Lin; Shen, Chia-Ning; Kuo, Ming-Ling; Su, Chien-Chang; Tseng, Ching-Ping; Yen, Tzu-Chen; Shen, Chia-Rui

    2009-12-01

    Asthma, a chronic helper T cell type 2-mediated inflammatory disease, is characterized by airway hyperresponsiveness and inflammation. Growing evidence suggests that increased expression of acidic mammalian chitinase (AMCase) may play a role in the pathogenesis of asthma. In the present study, we sought to develop an RNA interference approach to suppress allergic asthma in mice through silencing of AMCase expression. Mice sensitized with ovalbumin (OVA) were intratracheally administered a recombinant adeno-associated virus expressing short hairpin RNA (rAAV-shRNA) against AMCase. In OVA-sensitized mice, the development of allergic symptoms was significantly associated with elevated AMCase expression. After administration of rAAV-shRNA, there was a significant reduction of AMCase expression in the lung and in bronchoalveolar lavage fluid (BALF) cells of sensitized mice. Sensitized mice receiving rAAV-shRNA showed a significant improvement in allergic symptoms, including airway hyperresponsiveness (AHR), eosinophil infiltration, eotaxin, interleukin-13 secretion in BALF, and serum OVA-specific IgE level. Our data suggest the hyperexpression of AMCase in asthma can be suppressed by rAAV-mediated shRNA. Silencing AMCase expression by shRNA may be a promising therapeutic strategy in asthma.

  10. Intranasal sirna targeting c-kit reduces airway inflammation in experimental allergic asthma.

    PubMed

    Wu, Wei; Chen, Hui; Li, Ya-Ming; Wang, Sheng-Yu; Diao, Xin; Liu, Kai-Ge

    2014-01-01

    Allergic asthma is characterized by airway inflammation caused by infiltration and activation of inflammatory cells that produce cytokines. Many studies have revealed that c-kit, a proto-oncogene, and its ligand, stem cell factor (SCF), play an important role in the development of asthmatic inflammation. Intranasal small interference RNA (siRNA) nanoparticles targeting specific viral gene could inhibit airway inflammation. In this study, we assessed whether silencing of c-kit with intranasal small interference RNA could reduce inflammation in allergic asthma. A mouse model of experimental asthma was treated with intranasal administration of anti-c-kit siRNA to inhibit the expression of the c-kit gene. We assessed the inflammatory response in both anti-c-kit siRNA-treated and control mice. Local administration of siRNA effectively inhibited the expression of the c-kit gene and reduced airway mucus secretion and the infiltration of eosinophils in bronchoalveolar lavage fluid. Moreover, c-kit siRNA reduced the production of SCF, interleukin-4 (IL-4), and IL-5, but had no effect on interferon-γ (IFN-γ) generation. These results show that intranasal siRNA nanoparticles targeting c-kit can decrease the inflammatory response in experimental allergic asthma.

  11. CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation.

    PubMed

    Causton, Benjamin; Ramadas, Ravisankar A; Cho, Josalyn L; Jones, Khristianna; Pardo-Saganta, Ana; Rajagopal, Jayaraj; Xavier, Ramnik J; Medoff, Benjamin D

    2015-07-15

    Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-κB in AECs by allergens or secondary mediators via G protein-coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-κB activity in response to numerous stimuli. We have previously shown that caspase recruitment domain-containing membrane-associated guanylate kinase protein (CARMA)3 is specifically expressed in AECs and mediates NF-κB activation in these cells in response to stimulation with the GPCR agonist lysophosphatidic acid. In this study, we demonstrate that reduced levels of CARMA3 in normal human bronchial epithelial cells decreases the production of proasthmatic mediators in response to a panel of asthma-relevant GPCR ligands such as lysophosphatidic acid, adenosine triphosphate, and allergens that activate GPCRs such as Alternaria alternata and house dust mite. We then show that genetically modified mice with CARMA3-deficient AECs have reduced airway eosinophilia and proinflammatory cytokine production in a murine model of allergic airway inflammation. Additionally, we demonstrate that these mice have impaired dendritic cell maturation in the lung and that dendritic cells from mice with CARMA3-deficient AECs have impaired Ag processing. In conclusion, we show that AEC CARMA3 helps mediate allergic airway inflammation, and that CARMA3 is a critical signaling molecule bridging the innate and adaptive immune responses in the lung. PMID:26041536

  12. Effects of Ex Vivo y-Tocopherol on Airway Macrophage Function in Healthy and Mild Allergic Asthmatics

    EPA Science Inventory

    Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate y-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-med...

  13. Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model.

    PubMed

    Gao, Yi; Zhaoyu, Liu; Xiangming, Fang; Chunyi, Lin; Jiayu, Pan; Lu, Shen; Jitao, Chen; Liangcai, Chen; Jifang, Liu

    2016-09-01

    Abietic acid (AA), one of the terpenoids isolated from Pimenta racemosa var. grissea, has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-allergic effects of AA remain unclear. The aim of this study was to investigate the anti-allergic effects of AA in an ovalbumin (OVA)-induced asthma murine model. The model of mouse asthma was established by induction of OVA. AA (10, 20, 40mg/kg) was administered by oral gavage 1h after the OVA treatment on days 21 to 23. At 24h after the last challenge, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to assess pathological changes, cytokines production, and NF-κB expression. The results showed that AA attenuated lung histopathologic changes, inflammatory cells infiltration, and bronchial hyper-responsiveness. AA also inhibited OVA-induced the nitric oxide (NO), IL-4, IL-5, IL-13, and OVA-specific IgE production, as well as NF-κB activation. In conclusion, the current study demonstrated that AA exhibited protective effects against OVA-induced allergic asthma in mice and the possible mechanism was involved in inhibiting NF-κB activation. PMID:27318791

  14. Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats

    PubMed Central

    2010-01-01

    Background Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation. Methods Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge. Results Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30%) and TNF-α (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration. Conclusion Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction. PMID:20667094

  15. Role of Eosinophil Granulocytes in Allergic Airway Inflammation Endotypes.

    PubMed

    Amin, K; Janson, C; Bystrom, J

    2016-08-01

    Eosinophil granulocytes are intriguing members of the innate immunity system that have been considered important defenders during parasitic diseases as well as culprits during allergy-associated inflammatory diseases. Novel studies have, however, found new homoeostasis-maintaining roles for the cell. Recent clinical trials blocking different Th2 cytokines have uncovered that asthma is heterogeneous entity and forms different characteristic endotypes. Although eosinophils are present in allergic asthma with early onset, the cells may not be essential for the pathology. The cells are, however, likely disease causing in asthma with a late onset, which is often associated with chronic rhinosinusitis. Assessment of eosinophilia, fraction exhaled nitric oxide (FeNO) and periostin are markers that have emerged useful in assessing and monitoring asthma severity and endotype. Current scientific knowledge suggests that eosinophils are recruited by the inflammatory environment, activated by the innate interleukin (IL)-33 and prevented from apoptosis by both lymphocytes and innate immune cells such as type two innate immune cells. Eosinophils contain four specific granule proteins that exhibit an array of toxic and immune-modulatory activates. The granule proteins can be released by different mechanisms. Additionally, eosinophils contain a number of inflammatory cytokines and lipid mediators as well as radical oxygen species that might contribute to the disease both by the recruitment of other cells and the direct damage to supporting cells, leading to exacerbations and tissue fibrosis. This review aimed to outline current knowledge how eosinophils are recruited, activated and mediate damage to tissues and therapies used to control the cells. PMID:27167590

  16. Probiotics as Additives on Therapy in Allergic Airway Diseases: A Systematic Review of Benefits and Risks

    PubMed Central

    Das, Rashmi Ranjan; Naik, Sushree Samiksha; Singh, Meenu

    2013-01-01

    Background. We conducted a systematic review to find out the role of probiotics in treatment of allergic airway diseases.  Methods. A comprehensive search of the major electronic databases was done till March 2013. Trials comparing the effect of probiotics versus placebo were included. A predefined set of outcome measures were assessed. Continuous data were expressed as standardized mean difference with 95% CI. Dichotomous data were expressed as odds ratio with 95% CI. P value < 0.05 was considered as significant. Results. A total of 12 studies were included. Probiotic intake was associated with a significantly improved quality of life score in patients with allergic rhinitis (SMD −1.9 (95% CI −3.62, −0.19); P = 0.03), though there was a high degree of heterogeneity. No improvement in quality of life score was noted in asthmatics. Probiotic intake also improved the following parameters: longer time free from episodes of asthma and rhinitis and decrease in the number of episodes of rhinitis per year. Adverse events were not significant. Conclusion. As the current evidence was generated from few trials with high degree of heterogeneity, routine use of probiotics as an additive on therapy in subjects with allergic airway diseases cannot be recommended. PMID:23956972

  17. Allergic sensitization to ornamental plants in patients with allergic rhinitis and asthma.

    PubMed

    Aydin, Ömür; Erkekol, Ferda Öner; Misirloigil, Zeynep; Demirel, Yavuz Selim; Mungan, Dilşad

    2014-01-01

    Ornamental plants (OPs) can lead to immediate-type sensitization and even asthma and rhinitis symptoms in some cases. This study aimed to evaluate sensitization to OPs in patients with asthma and/or allergic rhinitis and to determine the factors affecting the rate of sensitization to OPs. A total of 150 patients with asthma and/or allergic rhinitis and 20 healthy controls were enrolled in the study. Demographics and disease characteristics were recorded. Skin-prick tests were performed with a standardized inhalant allergen panel. Skin tests by "prick-to-prick" method with the leaves of 15 Ops, which are known to lead to allergenic sensitization, were performed. Skin tests with OPs were positive in 80 patients (47.1%). There was no significant difference between OP sensitized and nonsensitized patients in terms of gender, age, number of exposed OPs, and duration of exposure. Skin test positivity rate for OPs was significantly high in atopic subjects, patients with allergic rhinitis, food sensitivity, and indoor OP exposure, but not in patients with pollen and latex allergy. Most sensitizing OPs were Yucca elephantipes (52.5%), Dieffenbachia picta (50.8%), and Euphorbia pulcherrima (47.5%). There was significant correlation between having Saintpaulia ionantha, Croton, Pelargonium, Y. elephantipes, and positive skin test to these plants. Sensitivity to OPs was significantly higher in atopic subjects and patients with allergic rhinitis, food allergy, and indoor OP exposure. Furthermore, atopy and food sensitivity were found as risk factors for developing sensitization to indoor plants. Additional trials on the relationship between sensitization to OPs and allergic symptoms are needed. PMID:24717779

  18. CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

    PubMed Central

    López-Pacheco, C.; Soldevila, G.; Du Pont, G.; Hernández-Pando, R.

    2016-01-01

    Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma. PMID:27795621

  19. Natural antibody repertoires: development and functional role in inhibiting allergic airway disease.

    PubMed

    Kearney, John F; Patel, Preeyam; Stefanov, Emily K; King, R Glenn

    2015-01-01

    In this review we discuss the effects of microbial exposure on the B cell repertoire. Neonatal exposure to conserved bacterial carbohydrates and phospholipids permanently reprograms the natural antibody repertoire directed toward these antigens by clonal expansion, alterations in clonal dominance, and increased serum antibody levels. These epitopes are present not only in bacterial cell walls, but also in common environmental allergens. Neonatal immunization with bacterial polysaccharide vaccines results in attenuated allergic airway responses to fungi-, house dust mite-, and cockroach-associated allergens in mouse models. The similarities between mouse and human natural antibody repertoires suggest that reduced microbial exposure in children may have the opposite effect, providing a potential mechanistic explanation for the hygiene hypothesis. We propose that understanding the effects of childhood infections on the natural antibody repertoire and the mechanisms of antibody-mediated immunoregulation observed in allergy models will lead to the development of prevention/interventional strategies for treatment of allergic asthma. PMID:25622195

  20. Acetaminophen Attenuates House Dust Mite-Induced Allergic Airway Disease in Mice.

    PubMed

    Smith, Gregory J; Thrall, Roger S; Cloutier, Michelle M; Manautou, Jose E; Morris, John B

    2016-09-01

    Epidemiologic evidence suggests that N-acetyl-para-aminophenol (APAP) may play a role in the pathogenesis of asthma, likely through pro-oxidant mechanisms. However, no studies have investigated the direct effects of APAP on the development of allergic inflammation. To determine the likelihood of a causal relationship between APAP and asthma pathogenesis, we explored the effects of APAP on inflammatory responses in a murine house dust mite (HDM) model of allergic airway disease. We hypothesized that APAP would enhance the development of HDM-induced allergic inflammation. The HDM model consisted of once daily intranasal instillations for up to 2 weeks with APAP or vehicle administration 1 hour prior to HDM during either week 1 or 2. Primary assessment of inflammation included bronchoalveolar lavage (BAL), cytokine expression in lung tissue, and histopathology. Contrary to our hypothesis, the effects of HDM treatment were substantially diminished in APAP-treated groups compared with controls. APAP-treated groups had markedly reduced airway inflammation: including decreased inflammatory cells in the BAL fluid, lower cytokine expression in lung tissue, and less perivascular and peribronchiolar immune cell infiltration. The anti-inflammatory effect of APAP was not abrogated by an inhibitor of cytochrome P450 (P450) metabolism, suggesting that the effect was due to the parent compound or a non-P450 generated metabolite. Taken together, our studies do not support the biologic plausibility of the APAP hypothesis that APAP use may contribute to the causation of asthma. Importantly, we suggest the mechanism by which APAP modulates airway inflammation may provide novel therapeutic targets for asthma. PMID:27402277

  1. The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation.

    PubMed

    Sy, Chandler B; Siracusa, Mark C

    2016-01-01

    Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects. It is reported that the majority of asthmas are associated with T helper type 2 (TH2) responses. In these patients, allergen challenge initiates the influx of TH2 cells in the airways leading to an increased production of TH2-associated cytokines and the promotion of allergy-induced asthma. Therefore, biologics that target this pathway may provide an alternative method to treat the allergic airway inflammation associated with asthma. As of now, only two biologics (omalizumab and mepolizumab), which target immunoglobulin E and interleukin-5, respectively, are FDA-approved and being prescribed to asthmatics. However, recent studies have reported that targeting other components of the TH2 response also show great promise. In this review, we will briefly describe the immunologic mechanisms underlying allergic asthma. Furthermore, we will discuss the current therapeutic strategies used to treat asthma including their limitations. Finally, we will highlight the benefits of using biologics to treat asthma-associated allergic airway inflammation with an emphasis on the potential of targeting cytokine alarmins, especially thymic stromal lymphopoietin. PMID:27378934

  2. The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation

    PubMed Central

    Sy, Chandler B.; Siracusa, Mark C.

    2016-01-01

    Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects. It is reported that the majority of asthmas are associated with T helper type 2 (TH2) responses. In these patients, allergen challenge initiates the influx of TH2 cells in the airways leading to an increased production of TH2-associated cytokines and the promotion of allergy-induced asthma. Therefore, biologics that target this pathway may provide an alternative method to treat the allergic airway inflammation associated with asthma. As of now, only two biologics (omalizumab and mepolizumab), which target immunoglobulin E and interleukin-5, respectively, are FDA-approved and being prescribed to asthmatics. However, recent studies have reported that targeting other components of the TH2 response also show great promise. In this review, we will briefly describe the immunologic mechanisms underlying allergic asthma. Furthermore, we will discuss the current therapeutic strategies used to treat asthma including their limitations. Finally, we will highlight the benefits of using biologics to treat asthma-associated allergic airway inflammation with an emphasis on the potential of targeting cytokine alarmins, especially thymic stromal lymphopoietin. PMID:27378934

  3. Investigating the Effects of Particulate Matter on House Dust Mite and Ovalbumin Allergic Airway Inflammation in Mice.

    PubMed

    Castañeda, Alejandro R; Pinkerton, Kent E

    2016-01-01

    Particulate matter (PM), a component of air pollution, has been shown to enhance allergen-mediated airway hypersensitivity and inflammation. Surprisingly, exposure to PM during the sensitization to allergen is sufficient to produce immunological changes that result in heightened inflammatory effects upon future allergen exposures (challenge) in the absence of PM. This suggests that PM has the ability to modulate the allergic immune response, thereby acting as an adjuvant by enhancing the immunological memory formed during the adaptive immune response; however, the mechanisms through which this occurs remain elusive. Establishing a reproducible animal model to study the PM-mediated immunotoxicological effects that enhance allergy, may provide insights to understand how air pollution activates the immune system and thereby modulates the pathophysiology of asthma. The basic protocol can be used to study various characteristics of air pollution, such as PM size, source, or chemical composition, to help elucidate how such features may affect the allergic response in a mouse model of asthma. Using a BALB/c model of acute exposure (14 days), mice are first sensitized with allergen and PM, and then subsequently challenged with allergen only. The endpoints of this basic protocol include the assessment of inflammation via cells recovered from broncho-alveolar lavage (BAL), histopathological analysis, gene expression profiles, and protein quantification of inflammatory markers. © 2016 by John Wiley & Sons, Inc. PMID:27145110

  4. Investigating the Effects of Particulate Matter on House Dust Mite and Ovalbumin Allergic Airway Inflammation in Mice.

    PubMed

    Castañeda, Alejandro R; Pinkerton, Kent E

    2016-05-04

    Particulate matter (PM), a component of air pollution, has been shown to enhance allergen-mediated airway hypersensitivity and inflammation. Surprisingly, exposure to PM during the sensitization to allergen is sufficient to produce immunological changes that result in heightened inflammatory effects upon future allergen exposures (challenge) in the absence of PM. This suggests that PM has the ability to modulate the allergic immune response, thereby acting as an adjuvant by enhancing the immunological memory formed during the adaptive immune response; however, the mechanisms through which this occurs remain elusive. Establishing a reproducible animal model to study the PM-mediated immunotoxicological effects that enhance allergy, may provide insights to understand how air pollution activates the immune system and thereby modulates the pathophysiology of asthma. The basic protocol can be used to study various characteristics of air pollution, such as PM size, source, or chemical composition, to help elucidate how such features may affect the allergic response in a mouse model of asthma. Using a BALB/c model of acute exposure (14 days), mice are first sensitized with allergen and PM, and then subsequently challenged with allergen only. The endpoints of this basic protocol include the assessment of inflammation via cells recovered from broncho-alveolar lavage (BAL), histopathological analysis, gene expression profiles, and protein quantification of inflammatory markers. © 2016 by John Wiley & Sons, Inc.

  5. Combination therapy with relaxin and methylprednisolone augments the effects of either treatment alone in inhibiting subepithelial fibrosis in an experimental model of allergic airways disease.

    PubMed

    Royce, Simon G; Sedjahtera, Amelia; Samuel, Chrishan S; Tang, Mimi L K

    2013-01-01

    Although CSs (corticosteroids) demonstrate potent effects in the control of airway inflammation in asthma, many patients continue to experience symptoms and AHR (airway hyper-responsiveness) despite optimal treatment with these agents, probably due to progressive airway remodelling. Identifying novel therapies that can target airway remodelling and/or airway reactivity may improve symptom control in these patients. We have demonstrated previously that the anti-fibrotic hormone RLN (relaxin) can reverse airway remodelling (epithelial thickening and subepithelial fibrosis) and AHR in a murine model of AAD (allergic airways disease). In the present study, we compared the effects of RLN with a CS (methylprednisolone) on airway remodelling and AHR when administered independently or in combination in the mouse AAD model. Female mice at 6-8 weeks of age were sensitized and challenged to OVA (ovalbumin) over a 9-week period and treated with methylprednisolone, RLN, a combination of both treatments or vehicle controls. Methylprednisolone was administered intraperitoneally on the same day as nebulization for 6 weeks, whereas recombinant human RLN-2 was administered via subcutaneously implanted osmotic mini-pumps from weeks 9-11. RLN or methylprednisolone alone were both able to significantly decrease subepithelial thickness and total lung collagen deposition; whereas RLN but not methylprednisolone significantly decreased epithelial thickness and AHR. Additionally, combination therapy with CS and RLN more effectively reduced subepithelial collagen thickness than either therapy alone. These findings demonstrate that RLN can modulate a broader range of airway remodelling changes and AHR than methylprednisolone and the combination of both treatments offers enhanced control of subepithelial fibrosis. PMID:22817662

  6. Interaction of vitamin E isoforms on asthma and allergic airway disease.

    PubMed

    Cook-Mills, Joan; Gebretsadik, Tebeb; Abdala-Valencia, Hiam; Green, Jeremy; Larkin, Emma K; Dupont, William D; Shu, Xiao Ou; Gross, Myron; Bai, Chunxue; Gao, Yu-Tang; Hartman, Terryl J; Rosas-Salazar, Christian; Hartert, Tina

    2016-10-01

    Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease.

  7. Interaction of vitamin E isoforms on asthma and allergic airway disease.

    PubMed

    Cook-Mills, Joan; Gebretsadik, Tebeb; Abdala-Valencia, Hiam; Green, Jeremy; Larkin, Emma K; Dupont, William D; Shu, Xiao Ou; Gross, Myron; Bai, Chunxue; Gao, Yu-Tang; Hartman, Terryl J; Rosas-Salazar, Christian; Hartert, Tina

    2016-10-01

    Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease. PMID:27257004

  8. Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma.

    PubMed

    Lee, Chen-Chen; Lee, Yueh-Lun; Wang, Chien-N; Tsai, Hsing-Chuan; Chiu, Chun-Lung; Liu, Leroy F; Lin, Hung-Yun; Wu, Reen

    2016-01-01

    The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation. PMID:26916919

  9. Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation.

    PubMed

    Scanlon, Seth T; Thomas, Seddon Y; Ferreira, Caroline M; Bai, Li; Krausz, Thomas; Savage, Paul B; Bendelac, Albert

    2011-09-26

    Airborne exposure to microbial cell wall lipids such as lipopolysaccharide triggers innate immune responses that regulate susceptibility to allergic airway inflammation. α-Glycosylceramides represent another widespread class of microbial lipids that directly stimulate innate-like, IL-4- and IL-13-producing, CD1d-restricted NKT cells. In this study, we demonstrate that NKT cells constitutively accumulate and reside in the microvasculature of the mouse lung. After a single airborne exposure to lipid antigen, they promptly extravasate to orchestrate the formation of peribronchiolar and interstitial lymphohistiocytic granulomas containing numerous eosinophils. Concomitant airborne exposure to ovalbumin (OVA) induces the priming of OVA-specific Th2 cells and IgE antibodies by the same dendritic cell coexpressing CD1d and MHC class II. Although NKT cell activation remains confined to the lipid-exposed lung and draining lymph nodes, Th2 cells recirculate and seed the lung of a parabiotic partner, conferring susceptibility to OVA challenge months after the initial exposure, in a manner independent of NKT cells and CD1d. Thus, transient recruitment and activation of lung-resident intravascular NKT cells can trigger long-term susceptibility to allergic airway inflammation.

  10. Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.

    PubMed Central

    Watanabe, A; Mishima, H; Renzi, P M; Xu, L J; Hamid, Q; Martin, J G

    1995-01-01

    Activated CD4+ helper T cells have been demonstrated in asthmatic airways and postulated to play a central role in eliciting allergic inflammation; direct evidence of their involvement seems to be lacking. We hypothesized that CD4+ T cells have the potential to induce allergic responses to antigen challenge, and tested this hypothesis in a model of allergic bronchoconstriction, the Brown Norway rat, using the approach of adoptive transfer. Animals were actively sensitized to either ovalbumin (OVA) or BSA and were used as donors of T cells. W3/25(CD4)+ or OX8(CD8)+ T cells were isolated from the cervical lymph nodes of sensitized donors and transferred to naive BN rats. 2 d after adoptive transfer recipient rats were challenged by OVA inhalation, and changes in lung resistance (RL), bronchoalveolar lavage (BAL) cells, and serum levels of antigen-specific IgE were studied. After OVA challenge recipients of OVA-primed W3/25+ T cells exhibited sustained increases in RL throughout the entire 8-h observation period and had significant bronchoalveolar lavage eosinophilia, which was detected by immunocytochemistry using an antimajor basic protein mAb. Recipients of BSA-primed W3/25+ T cells or OVA-primed OX8+ T cells failed to respond to inhaled OVA. OVA-specific immunoglobulin E was undetectable by ELISA or skin testing in any of the recipient rats after adoptive transfer. In conclusion, antigen-induced airway bronchoconstriction and eosinophilia were successfully transferred by antigen-specific W3/25+ T cells in Brown Norway rats. These responses were dependent on antigen-primed W3/25+ T cells and appeared to be independent of IgE-mediated mast cell activation. This study provides clear evidence for T cell mediated immune mechanisms in allergic airway responses in this experimental model. Images PMID:7657805

  11. Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation.

    PubMed

    Daniels, N J; Hyde, E; Ghosh, S; Seo, K; Price, K M; Hoshino, K; Kaisho, T; Okada, T; Ronchese, F

    2016-01-01

    Allergic airway inflammation is driven by the recognition of inhaled allergen by T helper type 2 (Th2) cells in the airway and lung. Allergen-specific cytotoxic T lymphocytes (CTLs) can strongly reduce airway inflammation, however, the mechanism of their inhibitory activity is not fully defined. We used mouse models to show that allergen-specific CTLs reduced early cytokine production by Th2 cells in lung, and their subsequent accumulation and production of interleukin (IL)-4 and IL-13. In addition, treatment with specific CTLs also increased the proportion of caspase(+) dendritic cells (DCs) in mediastinal lymph node (MLN), and decreased the numbers of CD103(+) and CD11b(+) DCs in the lung. This decrease required expression of the cytotoxic mediator perforin in CTLs and of the appropriate MHC-antigen ligand on DCs, suggesting that direct CTL-DC contact was necessary. Lastly, lung imaging experiments revealed that in airway-challenged mice XCR1-GFP(+) DCs, corresponding to the CD103(+) DC subset, and XCR1-GFP(-) CD11c(+) cells, which include CD11b(+) DCs and alveolar macrophages, both clustered in the areas surrounding the small airways and were closely associated with allergen-specific CTLs. Thus, allergen-specific CTLs reduce allergic airway inflammation by depleting CD103(+) and CD11b(+) DC populations in the lung, and may constitute a mechanism through which allergic immune responses are regulated.

  12. Effects of airway exposure to di-(2-ethylhexyl) phthalate on allergic rhinitis.

    PubMed

    He, Miao; Inoue, Ken-Ichiro; Yoshida, Seiichi; Tanaka, Michitaka; Takano, Hirohisa; Sun, Guifan; Ichinose, Takamichi

    2013-06-01

    Recent epidemiological studies have suggested a positive link between atopy morbidity and exposure to phthalate esters, which are environmental chemicals mainly involved in house dust. Nevertheless, experimental studies applying several allergic in vivo models (in addition to epidemiological studies) are needed to prove the precise correlation between phthalates and facilitation of the allergic response/pathophysiology. Among the phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used in flexible polyvinyl chloride products, including vinyl flooring and wall covering, and has been widely suggested to have immunomodulating potential. In the present study, we examined the effects of airway exposure to DEHP on allergen (ovalbumin: OVA)-induced rhinitis in mice. The repeated administration of OVA via an intranasal route induced nasal inflammation characterized by the infiltration of granulocytes (neutrophils and eosinophils) into the nasal cavity. In this experimental setting, DEHP did not exaggerate OVA-related inflammatory pathology. However, local (nasal) IL-13 levels were significantly higher in mice treated with allergen plus DEHP than with allergen alone. Taken together, phthalate esters including DEHP have the potential to exacerbate the allergic milieu in the nasal system, as well as dermal and respiratory systems. PMID:23672524

  13. Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

    PubMed

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

    2016-03-01

    Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway. PMID:26826245

  14. Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

    PubMed

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

    2016-03-01

    Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway.

  15. Clinical and allergic sensitization characteristics of allergic rhinitis among the elderly population in Istanbul, Turkey.

    PubMed

    Ozturk, Ayse Bilge; Ozyigit, Leyla Pur; Olmez, Merve Ozata

    2015-04-01

    Prevalence of allergic rhinitis (AR) in elderly population in Turkey is not known. Studies on the prevalence and features of allergy in older adults are needed to identify safe and effective diagnostic/therapeutic methods for elderly AR patients. We aimed to identify the clinical and allergic characteristics of sensitization to aeroallergens among individuals aged ≥60 years with allergic rhinitis admitted to an allergy outpatient clinic in Istanbul. Of 109 patients, 33.9 % were atopic. Sixty-five percent of subjects were sensitized to Dermatophagoides pteronyssinus, 17 % to a grass-pollen mixture, 8 % to Aspergillus fumigatus, and 8 % to Blattella germanica. There was no difference between mono- and polysensitized patients in terms of the duration of rhinitis and symptom severity. No significant difference was observed between the two groups according to age, sex, smoking status, AR onset (<40 or ≥40 years), or duration/severity of disease. There was no significant difference between the two groups in the prevalence of asthma and conjunctivitis, (p = 0.256). Atopic dermatitis/eczema was more prevalent in those with AR (p = 0.046). Clinical characteristics of AR in the elderly could be different from those in non-allergic patients, and the prevalence of allergy may be higher than expected.

  16. Tropomyosin sensitization in house dust mite allergic patients.

    PubMed

    Becker, Sven; Gröger, Moritz; Canis, Martin; Pfrogner, Elisabeth; Kramer, Matthias F

    2012-04-01

    The growing popularity and frequency of consumption of seafood is accompanied by an increasing number of adverse reactions reported in literature. Allergic reactions to seafood can generate a variety of symptoms ranging from a mild oral allergy syndrome to keen anaphylactic reactions. Tropomyosin, the major shellfish allergen is regarded to be responsible for clinical cross-reactivity to inhaled house dust mites. The aim of the study was to investigate the prevalence of sensitization to tropomyosin in house dust mite allergic patients in southern Bavaria and to compare the results with allergic symptoms. Sera of house dust mite allergic patients (positive skin prick test, allergen-specific IgE and intranasal provocation) were screened for IgE antibodies to tropomyosin (Der p 10). Patients were contacted by phone to evaluate allergic symptoms when consuming seafood. IgE antibodies to house dust mite tropomyosin (Der p 10) could be found in 4 out of 93 sera (4.3%). Two of these four patients (50%) showed itching and swelling of oral mucosa accompanied by bronchial obstruction after consumption of shrimp. Two patients had no problems when eating seafood. None of the seronegative patients complained about any health problems during or after consumption of seafood. In conclusion, cross-reactivity to tropomyosin in house dust mite allergic patients in southern Bavaria, Germany is rarer than suspected. Beside the direct allergic reactions, a further part of reactions to seafood must therefore be ascribed to other mechanisms such as intoxication or intolerance to, e.g. additives in the food product.

  17. Respiratory responses of subjects with allergic rhinitis to ozone exposure and their relationship to nonspecific airway reactivity

    SciTech Connect

    McDonnell, W.F.; Horstman, D.H.; Abdul-Salaam, S.; Raggio, L.J.; Green, J.A.

    1987-12-01

    Ozone exposure in man produces changes in respiratory function and symptoms. There is a large degree of unexplained intersubject variability in the magnitude of these responses. There is concern that individuals with chronic respiratory diseases may also be more responsive to ozone than normal individuals. The purpose of this study was to describe the responses of subjects with allergic rhinitis to ozone exposure and to compare these responses to those previously observed in normal individuals. A further purpose was to measure the association of baseline nonspecific airway reactivity with changes in lung function and respiratory symptoms following ozone exposure. A group of 26 nonasthmatic subjects with allergic rhinitis performed a bronchial inhalation challenge with histamine and subsequently underwent two hour exposures to both clean air and to 0.18 part per million ozone with alternating periods of rest and heavy exercise. The airway reactivity of this group of subjects was no greater than that of a comparable group of subjects without allergic rhinitis. The respiratory responses of these subjects to ozone exposure were similar to those previously reported for subjects without allergic rhinitis with the exception that the allergic rhinitis subjects appeared to have a modestly increased bronchoconstrictor response compared to normals. Furthermore, we observed no significant relationships between nonspecific airway reactivity and response to ozone as measured by changes in lung function or the induction of symptoms.

  18. A novel microbe-based treatment that attenuates the inflammatory profile in a mouse model of allergic airway disease

    PubMed Central

    Bazett, Mark; Biala, Agnieszka; Huff, Ryan D.; Bosiljcic, Momir; Gunn, Hal; Kalyan, Shirin; Hirota, Jeremy A.

    2016-01-01

    There is an unmet need for effective new and innovative treatments for asthma. It is becoming increasingly evident that bacterial stimulation can have beneficial effects at attenuating allergic airway disease through immune modulation. Our aim was to test the ability of a novel inactivated microbe-derived therapeutic based on Klebsiella (KB) in a model of allergic airway disease in mice. BALB/c mice were exposed intranasally to house dust mite (HDM) for two weeks. Mice were treated prophylactically via subcutaneous route with either KB or placebo for one week prior to HDM exposure and throughout the two week exposure period. 24 hours after the last exposure, lungs were analysed for inflammatory cell infiltrate, gene expression, cytokine levels, goblet cell metaplasia, and serum was analysed for allergen-specific serum IgE levels. HDM exposed mice developed goblet cell hyperplasia, elevated allergen-specific serum IgE, airway eosinophilia, and a concomitant increase in TH2 cytokines including IL-4, IL-13 and IL-5. Treatment with KB attenuated HDM-mediated airway eosinophilia, total bronchoalveolar lavage (BAL) cell numbers, BAL TH2 cytokine production, and goblet cell metaplasia. Our prophylactic intervention study illustrates the potential of subcutaneous treatment with bacterial derived biologics as a promising approach for allergic airway disease treatment. PMID:27734946

  19. Protective effect of curcumin on acute airway inflammation of allergic asthma in mice through Notch1-GATA3 signaling pathway.

    PubMed

    Chong, Lei; Zhang, Weixi; Nie, Ying; Yu, Gang; Liu, Liu; Lin, Li; Wen, Shunhang; Zhu, Lili; Li, Changchong

    2014-10-01

    Curcumin, a natural product derived from the plant Curcuma longa, has been found to have anti-inflammatory, antineoplastic and antifibrosis effects. It has been reported that curcumin attenuates allergic airway inflammation in mice through inhibiting NF-κB and its downstream transcription factor GATA3. It also has been proved the antineoplastic effect of curcumin through down-regulating Notch1 receptor and its downstream nuclear transcription factor NF-κB levels. In this study, we aimed to investigate the anti-inflammatory effect of curcumin on acute allergic asthma and its underlying mechanisms. 36 male BALB/c mice were randomly divided into four groups (normal, asthma, asthma+budesonide and asthma+curcumin groups). BALF (bronchoalveolar lavage fluid) and lung tissues were analyzed for airway inflammation and the expression of Notch1, Notch2, Notch3, Notch4 and the downstream transcription factor GATA3. Our findings showed that the levels of Notch1 and Notch2 receptors were up-regulated in asthma group, accompanied by the increased expression of GATA3. But the expression of Notch2 receptor was lower than Notch1 receptor. Curcumin pretreatment improved the airway inflammatory cells infiltration and reversed the increasing levels of Notch1/2 receptors and GATA3. Notch3 receptor was not expressed in all of the four groups. Notch4 receptor protein and mRNA expression level in the four groups had no significant differences. The results of the present study suggested that Notch1 and Notch2 receptor, major Notch1 receptor, played an important role in the development of allergic airway inflammation and the inhibition of Notch1-GATA3 signaling pathway by curcumin can prevent the development and deterioration of the allergic airway inflammation. This may be a possible therapeutic option of allergic asthma.

  20. Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells.

    PubMed

    Secor, Eric R; Szczepanek, Steven M; Castater, Christine A; Adami, Alexander J; Matson, Adam P; Rafti, Ektor T; Guernsey, Linda; Natarajan, Prabitha; McNamara, Jeffrey T; Schramm, Craig M; Thrall, Roger S; Silbart, Lawrence K

    2013-01-01

    The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). However, sBr's effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL), spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes). OVA-specific IgE and OVA TET(+) cells were decreased. sBr reduced CD11c(+) dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena.

  1. Mechanisms and characteristics of airway sensitization to indoor allergens.

    PubMed

    Liccardi, G; Cazzola, M; Russo, M; Gilder, J A; D'Amato, M; D'Amato, G

    2001-02-01

    The increasing prevalence of allergic respiratory diseases, and particularly of bronchial asthma, has been linked to changes induced by human activities in outdoor and indoor environments. People living in industrialized countries spend most of their time indoors: in private homes, offices and means of transport. Indoor environments are not a refuge from outdoor air pollution. Modern systems for energy saving such as insulated windows and doors reduce the indoor natural ventilation and consequently increase the rate of indoor humidity. These conditions may determine an increase in the level of indoor pollutants (tobacco smoke, gases produced by cooling processes etc.) and of allergens derived from mites, domestic animals and cockroaches. Upholstered furniture, wall-to-wall carpets, central heating systems and/or humidifiers may also contribute to the growth of mite populations. The increasing levels of exposure to pollutants and allergens in indoor environments represents a risk factor for the development of airway sensitization, especially if these materials are inhaled early in life. The major cat allergen Fel d 1 is considered an ubiquitous allergen, since it has been found in many indoor environments where a cat has never been kept. The clothing of cat owners seems to help spread Fel d 1 in cat-free environments. Sensitization to cockroach allergens is very common in patients living in urban areas where unhygenic conditions may favour the growth of cockroach populations. Monitoring of the levels of allergens and strategies of allergen and pollutant avoidance in indoor environments are the main ways to reduce the prevalence of respiratory allergies induced by these materials.

  2. GS143, an I{kappa}B ubiquitination inhibitor, inhibits allergic airway inflammation in mice

    SciTech Connect

    Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie; Kagami, Shin-ichiro; Suto, Akira; Ikeda, Kei; Watanabe, Norihiko; Iwamoto, Itsuo; Furuichi, Yasuhiro; Nakajima, Hiroshi

    2008-09-26

    Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-{kappa}B (NF-{kappa}B) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of I{kappa}B ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-{kappa}B activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil and lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that I{kappa}B ubiquitination inhibitor may have therapeutic potential against asthma.

  3. Breathing hot humid air induces airway irritation and cough in patients with allergic rhinitis.

    PubMed

    Khosravi, Mehdi; Collins, Paul B; Lin, Ruei-Lung; Hayes, Don; Smith, Jaclyn A; Lee, Lu-Yuan

    2014-07-01

    We studied the respiratory responses to an increase in airway temperature in patients with allergic rhinitis (AR). Responses to isocapnic hyperventilation (40% of maximal voluntary ventilation) for 4min of humidified hot air (HA; 49°C) and room air (RA; 21°C) were compared between AR patients (n=7) and healthy subjects (n=6). In AR patients, cough frequency increased pronouncedly from 0.10±0.07 before to 2.37±0.73 during, and 1.80±0.79coughs/min for the first 8min after the HA challenge, but not during the RA challenge. In contrast, neither HA nor RA had any significant tussive effect in healthy subjects. The HA challenge also caused respiratory discomfort (mainly throat irritation) measured by the handgrip dynamometry in AR patients, but not in healthy subjects. Bronchoconstriction was not detected after the HA challenge in either group of subjects. In conclusion, hyperventilation of HA triggered vigorous cough response and throat irritation in AR patients, indicating the involvement of sensory nerves innervating upper airways.

  4. Xanthii Fructus inhibits allergic response in the ovalbumin-sensitized mouse allergic rhinitis model

    PubMed Central

    Gwak, Nam-Gil; Kim, Eun-Young; Lee, Bina; Kim, Jae-Hyun; Im, Yong-Seok; Lee, Ka-Yeon; Jun-Kum, Chang; Kim, Ho-Seok; Cho, Hyun-Joo; Jung, Hyuk-Sang; Sohn, Youngjoo

    2015-01-01

    Background: Xanthii Fructus (XF) is widely used in traditional anti-bacterial and anti-inflammatory Asian medicine. Allergic rhinitis is a common inflammatory disease characterized by markedly increased levels of anti-inflammatory factors and the recruitment of inflammatory cells into the nasal mucosa. We investigated the effects of XF in the allergen-induced rhinitis model. Materials and Methods: Following ovalbumin (OVA)/alum intraperitoneal injection on days 0, 7 and 14, the BALB/c mice (albino, laboratory-bred strain of the house mice) were challenged intranasally with OVA for 10 days a week after the last sensitization. The number of sneezes was recorded for 10 days; additionally, the levels of cytokines, histamine, immunoglobulin E (IgE) and OVA-specific serum IgE were estimated. Eosinophil infiltration, thickness of nasal mucosa and expression of caspase-1 were determined by immunohistochemistry. We also evaluated the effect of XF on the phosphorylation of nuclear factor kappa-B (NF-κB) and inhibitor of nuclear factor kappa B-alpha (IκB-α) in human mast cell-1 (HMC-1), by Western blotting. Results: The administration of XF significantly decreased sneezing and the serum levels of histamine, IgE, OVA-specific IgE, and cytokines such as tumor necrosis factor-alpha (TNF-α), interleukine-1 beta (IL-1β), IL-5, IL-6, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2). XF inhibited the changes in thickness of the nasal septum, influx of eosinophils and expression of capase-1. In addition, XF inhibited the phosphorylation of IκB-α and NF-κB in phorbol-myristate-acetate plus calcium ionophore A23187 (A23187) stimulated HMC-1. Conclusion: This study suggests that XF acts a potent anti-allergic drug which alleviates the allergic responses in ovalbumin-sensitized mouse allergic rhinitis model. PMID:26664025

  5. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2015-12-07

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk.

  6. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2016-02-01

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. PMID:26644379

  7. Antigen Sensitization Influences Organophosphorus Pesticide–Induced Airway Hyperreactivity

    PubMed Central

    Proskocil, Becky J.; Bruun, Donald A.; Lorton, Jesse K.; Blensly, Kirsten C.; Jacoby, David B.; Lein, Pamela J.; Fryer, Allison D.

    2008-01-01

    Background Recent epidemiologic studies have identified organophosphorus pesticides (OPs) as environmental factors potentially contributing to the increase in asthma prevalence over the last 25 years. In support of this hypothesis, we have demonstrated that environmentally relevant concentrations of OPs induce airway hyperreactivity in guinea pigs. Objectives Sensitization to allergen is a significant contributing factor in asthma, and we have shown that sensitization changes virus-induced airway hyperreactivity from an eosinophil-independent mechanism to one mediated by eosinophils. Here, we determine whether sensitization similarly influences OP-induced airway hyperreactivity. Methods Nonsensitized and ovalbumin-sensitized guinea pigs were injected subcutaneously with the OP parathion (0.001–1.0 mg/kg). Twenty-four hours later, animals were anesthetized and ventilated, and bronchoconstriction was measured in response to either vagal stimulation or intravenous acetylcholine. Inflammatory cells and acetylcholinesterase activity were assessed in tissues collected immediately after physiologic measurements. Results Ovalbumin sensitization decreased the threshold dose for parathion-induced airway hyperreactivity and exacerbated parathion effects on vagally induced bronchoconstriction. Pretreatment with antibody to interleukin (IL)-5 prevented parathion-induced hyperreactivity in sensitized but not in nonsensitized guinea pigs. Parathion did not increase the number of eosinophils in airways or the number of eosinophils associated with airway nerves nor did it alter eosinophil activation as assessed by major basic protein deposition. Conclusions Antigen sensitization increases vulnerability to parathion-induced airway hyperreactivity and changes the mechanism to one that is dependent on IL-5. Because sensitization to allergens is characteristic of 50% of the general population and 80% of asthmatics (including children), these findings have significant implications for

  8. Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice.

    PubMed Central

    Zuany-Amorim, C; Hailé, S; Leduc, D; Dumarey, C; Huerre, M; Vargaftig, B B; Pretolani, M

    1995-01-01

    This report examines the effect of recombinant murine (rm) IL-10 on antigen-induced cellular recruitment into the airways of sensitized Balb/c mice. The intranasal instillation of 10 micrograms ovalbumin induced an early (6-24 h) increase in the number of neutrophils, and a late rise (24-96 h) in that of eosinophils in the bronchoalveolar lavage (BAL) fluid and bronchial tissue. A single intranasal instillation of 0.01-0.1 microgram of rmIL-10, administered concurrently with ovalbumin, but not 1 or 3 h thereafter, dose-dependently inhibited both airway neutrophilia and eosinophilia. This phenomenon was suppressed by treating the sensitized mice with 1 mg/mouse of a neutralizing anti-IL-10 mAb, which increased significantly ovalbumin-induced neutrophil and eosinophil accumulation in the BAL fluid. These results suggest that antigen stimulation may trigger the in vivo generation of IL-10, which, in turn, participates in the leukocyte infiltration into the airways. rmIL-10 also reduced TNF-alpha release in the BAL fluid observed 1 and 3 h after antigen challenge. Furthermore, the intranasal instillation of an anti-TNF-alpha antiserum to sensitized mice markedly reduced ovalbumin-induced neutrophil and eosinophil accumulation in the BAL fluid. These findings indicate that leukocyte infiltration into the airways of antigen-challenged mice is regulated by IL-10. Furthermore, inhibition of TNF-alpha production by rmIL-10 suggests that allergic airway inflammation and TNF-alpha formation are parallel events in this model. Images PMID:7769104

  9. Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics.

    PubMed

    Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

    2015-01-01

    Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body's response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction.

  10. Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics

    PubMed Central

    Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

    2015-01-01

    Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body’s response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction. PMID:25922579

  11. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease. PMID:18160846

  12. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

  13. [Sensitization to granary mites in patients with allergic diseases].

    PubMed

    Golysheva, M A

    1991-01-01

    As many as 71 patients selected from a group of 550 patients suffering from allergic diseases, sensitized to the house dust mites Dermatophagoides pteronyssinus were examined. A study was made of the presence of allergen-specific IgE antibodies against house dust mites, storage mites (7 species altogether) using allergenic discs and commercial kits RAST (Pharmacia, Sweden). The group under examination mostly manifested sensitization to the house dust mites: Dermatophagoides ferinae (80%), Euroglyphus maynei (55%); storage mites: Acarus siro (45%), Lepidoglyphus destructor (35%). The latter one possesses the most powerful allergenic properties as compared to the acaroid mites of other types. The elevated sensitivity to storage mites is encountered among adults and children living both in Moscow and other regions (urban and rural). The problem of sensitization to storage mites in the USSR mandates thorough studies, which will enable the treatment and diagnostic agents to be designed and introduced into practice.

  14. Allergic and nonallergic interactions between house dust mite allergens and airway mucosa.

    PubMed

    Roche, N; Chinet, T C; Huchon, G J

    1997-03-01

    Asthma and allergy are extremely frequent diseases, affecting 5-10% and 30% of the population, respectively. The prevalence of asthma has increased in many developed countries, which may be due to several factors, including increased exposure to house dust mite (HDM) allergens. HDM to which humans are most frequently sensitized are Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei. These mites multiply in carpets, bedding and upholstered furniture in a hot and humid atmosphere. The allergens are digestive enzymes of the mites. Several epidemiological studies have shown that an increase in exposure to HDMs is associated with an increase in the prevalence of sensitization and asthma, whereas mite avoidance leads to a decrease in respiratory symptoms of sensitized asthmatic subjects. Sensitized subjects have specific immunoglobulin G and E (IgG and IgE) humoral responses, as well as proliferative T-cell responses to HDM allergens. Experimental exposure to HDM allergens induces bronchoalveolar inflammatory responses, that are characterized by the recruitment and activation of eosinophils, mastocytes, neutrophils, monocytes and lymphocytes. The cysteine protease activity of Der p 1 (a major allergen of D. pteronyssinus) has been shown to increase airway mucosal permeability, and may thereby contribute to the pathogenesis of airway inflammation and hyperresponsiveness by nonimmunological mechanisms. These epidemiological and experimental data support the recommendations for mite avoidance, especially in persons at high risk of developing asthma.

  15. Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection-Induced Severe Allergic Airway Disease.

    PubMed

    Starkey, Malcolm R; Nguyen, Duc H; Brown, Alexandra C; Essilfie, Ama-Tawiah; Kim, Richard Y; Yagita, Hideo; Horvat, Jay C; Hansbro, Philip M

    2016-04-01

    Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function, and the development of more severe allergic airway disease in later life.

  16. Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice

    PubMed Central

    Cruz, Fernanda F.; Borg, Zachary D.; Goodwin, Meagan; Sokocevic, Dino; Wagner, Darcy E.; Coffey, Amy; Antunes, Mariana; Robinson, Kristen L.; Mitsialis, S. Alex; Kourembanas, Stella; Thane, Kristen; Hoffman, Andrew M.; McKenna, David H.; Rocco, Patricia R.M.

    2015-01-01

    An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow-derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic-mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, both CM and EVs from human MSCs (hMSCs) were generally more potent than those from mouse MSCs (mMSCs) in most of the outcome measures. The weak cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride was found to inhibit release of both soluble mediators and EVs, fully negating effects of systemically administered hMSCs but only partly inhibited the ameliorating effects of mMSCs. These results demonstrate potent xenogeneic effects of CM and EVs from hMSCs in an immunocompetent mouse model of allergic airway inflammation and they also show differences in mechanisms of action of hMSCs versus mMSCs to mitigate AHR and lung inflammation in this model. Significance There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)-based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the

  17. Schistosoma mansoni Venom Allergen Like Proteins Present Differential Allergic Responses in a Murine Model of Airway Inflammation

    PubMed Central

    Farias, Leonardo Paiva; Rodrigues, Dunia; Cunna, Vinicius; Rofatto, Henrique Krambeck; Faquim-Mauro, Eliana L.; Leite, Luciana C. C.

    2012-01-01

    Background The Schistosoma mansoni Venom-Allergen-Like proteins (SmVALs) are members of the SCP/TAPS (Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, which may be important in the host-pathogen interaction. Some of these molecules were suggested by us and others as potential immunomodulators and vaccine candidates, due to their functional classification, expression profile and predicted localization. From a vaccine perspective, one of the concerns is the potential allergic effect of these molecules. Methodology/Principal Findings Herein, we characterized the putative secreted proteins SmVAL4 and SmVAL26 and explored the mouse model of airway inflammation to investigate their potential allergenic properties. The respective recombinant proteins were obtained in the Pichia pastoris system and the purified proteins used to produce specific antibodies. SmVAL4 protein was revealed to be present only in the cercarial stage, increasing from 0–6 h in the secretions of newly transformed schistosomulum. SmVAL26 was identified only in the egg stage, mainly in the hatched eggs' fluid and also in the secretions of cultured eggs. Concerning the investigation of the allergic properties of these proteins in the mouse model of airway inflammation, SmVAL4 induced a significant increase in total cells in the bronchoalveolar lavage fluid, mostly due to an increase in eosinophils and macrophages, which correlated with increases in IgG1, IgE and IL-5, characterizing a typical allergic airway inflammation response. High titers of anaphylactic IgG1 were revealed by the Passive Cutaneous Anaphylactic (PCA) hypersensitivity assay. Additionally, in a more conventional protocol of immunization for vaccine trials, rSmVAL4 still induced high levels of IgG1 and IgE. Conclusions Our results suggest that members of the SmVAL family do present allergic properties; however, this varies significantly and therefore should be considered in the design of a schistosomiasis vaccine

  18. Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease.

    PubMed

    Foong, Rachel E; Bosco, Anthony; Troy, Niamh M; Gorman, Shelley; Hart, Prue H; Kicic, Anthony; Zosky, Graeme R

    2016-09-01

    Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.

  19. Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation.

    PubMed

    Elhaik Goldman, Shirin; Moshkovits, Itay; Shemesh, Avishai; Filiba, Ayelet; Tsirulsky, Yevgeny; Vronov, Elena; Shagan, Marilou; Apte, Ron N; Benharroch, D Aniel; Karo-Atar, Danielle; Dagan, Ron; Munitz, Ariel; Mizrachi Nebenzahl, Yaffa; Porgador, Angel

    2016-01-01

    The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp) mice in comparison to OVA immunized wild type (NCR1+/+) and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL) revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils' (CCL24) and Th2 CD4+ T-cells' chemoattractants (CCL17, and CCL24) in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation. PMID:27580126

  20. Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

    PubMed Central

    Elhaik Goldman, Shirin; Moshkovits, Itay; Shemesh, Avishai; Filiba, Ayelet; Tsirulsky, Yevgeny; Vronov, Elena; Shagan, Marilou; Apte, Ron N.; Benharroch, D aniel; Karo-Atar, Danielle; Dagan, Ron; Munitz, Ariel

    2016-01-01

    The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp) mice in comparison to OVA immunized wild type (NCR1+/+) and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL) revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils’ (CCL24) and Th2 CD4+ T-cells’ chemoattractants (CCL17, and CCL24) in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation. PMID:27580126

  1. Evaluation of Furfuryl Alcohol Sensitization Potential Following Dermal and Pulmonary Exposure: Enhancement of Airway Responsiveness

    PubMed Central

    Franko, Jennifer; Jackson, Laurel G.; Hubbs, Ann; Kashon, Michael; Meade, B. J.; Anderson, Stacey E.

    2015-01-01

    Furfuryl alcohol is considered by the U.S. Environmental Protection Agency to be a high volume production chemical, with over 1 million pounds produced annually. Due to its high production volume and its numerous industrial and consumer uses, there is considerable potential for work-related exposure, as well as exposure to the general population, through pulmonary, oral, and dermal routes of exposure. Human exposure data report a high incidence of asthma in foundry mold workers exposed to furan resins, suggesting potential immunologic effects. Although furfuryl alcohol was nominated and evaluated for its carcinogenic potential by the National Toxicology Program, studies evaluating its immunotoxicity are lacking. The studies presented here evaluated the immunotoxic potential of furfuryl alcohol following exposure by the dermal and pulmonary routes using a murine model. When tested in a combined irritancy local lymph node assay, furfuryl alcohol was identified to be an irritant and mild sensitizer (EC3 = 25.6%). Pulmonary exposure to 2% furfuryl alcohol resulted in enhanced airway hyperreactivity, eosinophilic infiltration into the lungs, and enhanced cytokine production (IL-4, IL-5, and interferon-γ) by ex vivo stimulated lung-associated draining lymphoid cells. Airway hyperreactivity and eosinophilic lung infiltration were augmented by prior dermal exposure to furfuryl alcohol. These results suggest that furfuryl alcohol may play a role in the development of allergic airway disease and encourage the need for additional investigation. PMID:22003193

  2. Allergen-triggered airway hyperresponsiveness and lung pathology in mice sensitized with the biopesticide Metarhizium anisopliae.

    PubMed

    Ward, M D; Madison, S L; Sailstad, D M; Gavett, S H; Selgrade, M K

    2000-02-21

    Metarhizium anisopliae is an entomopathogenic fungus recently licensed for indoor control of cockroaches, a major source of allergens. While M. anisopliae has been shown to be non-infectious and non-toxic to mammals there has been only limited research on potential allergenicity. Using a mouse model, we previously demonstrated allergic immune and inflammatory responses to this agent. The present study was designed to determine whether these responses were associated with changes in pulmonary responses, lung pathology, and the cytokine profile in bronchoalveolar lavage fluid (BALF). Soluble factors from fungal components were combined in equal protein amounts to form M. anisopliae crude antigen (MACA). BALB/C mice were intratracheally (i.t.) challenged with 10 microg MACA 14 days post intraperitoneal sensitization with 25 microg fungal antigen in aluminum hydroxide adjuvant. Physiological and cellular changes were examined. The mice were tested for airway hyperresponsiveness before (No Chal) and after (1, 3, and 8 days post challenge (DPIT)) MACA IT challenge. Subsequently, serum, BALF and the lungs were harvested. All treatment groups concurrently demonstrated significant non-specific pulmonary inflammation (neutrophil influx) and increased pulmonary sensitivity to methacholine (Mch) at 1 DPIT MACA challenge. Where as both adjuvant treated and naïve mice airway responses had returned to near normal levels by 3 DPIT, mice which were previously sensitized with MACA were still hyperresponsive to Mch challenge at 3 and 8 DPIT. This hyperresponsiveness correlates with eosinophil and lymphocyte influx, which is maximal at 3 DPIT and still elevated at 8 DPIT. Interleukin (IL) 5 was elevated for all treatment groups at 1 DPIT but only the MACA sensitized mice maintained elevated levels for both 3 and 8 DPIT. Furthermore, MACA sensitized mice had a more extensive inflammatory histopathology at all examined time points with peribronchial and perivascular infiltrates, like

  3. The S1P/S1PR2 axis regulates early airway T cell infiltration in murine mast cell-dependent acute allergic responses

    PubMed Central

    Oskeritzian, Carole A.; Hait, Nitai C.; Wedman, Piper; Chumanevich, Alena; Kolawole, Elizabeth M.; Price, Megan M.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Ryan, John J.; Milstien, Sheldon; Sabbadini, Roger; Spiegel, Sarah

    2014-01-01

    Background Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid produced by mast cells (MC) upon cross-linking of their high affinity receptors for IgE by antigen (Ag) that can amplify MC responses by binding to its S1P receptors. Acute MC-dependent allergic reaction can lead to systemic shock but the early events of its development in lung tissues have not been investigated, and S1P functions in the onset of allergic processes remain to be examined. Objective We used a highly specific neutralizing anti-S1P antibody (mAb) and an S1P receptor 2 (S1PR2) antagonist, JTE-013, to study S1P and S1PR2 signaling contributions to MC- and IgE-dependent airway allergic responses in mice within minutes after Ag challenge. Methods Allergic reaction was triggered by a single intraperitoneal (i.p.) dose of Ag in sensitized mice pre-treated i.p. with anti-S1P or isotype control mAb, or JTE-013 or vehicle prior to Ag challenge. Results Kinetics experiments revealed early pulmonary infiltration of mostly T cells around blood vessels of sensitized mice 20 minutes post-Ag exposure. Pre-treatment with anti-S1P mAb inhibited in vitro MC activation, as well as in vivo development of airway infiltration and MC activation, reducing serum levels of histamine, cytokines and the chemokines MCP-1/CCL2, MIP-1α/CCL3 and RANTES/CCL5. S1PR2 antagonism or deficiency, or MC deficiency recapitulated these results. Both in vitro and in vivo experiments demonstrated MC S1PR2 dependency for chemokine release and the necessity for signal transducer and activator of transcription 3 (Stat3) activation. Conclusion Activation of S1PR2 by S1P and downstream Stat3 signaling in MC regulate early T cell recruitment to antigen-challenged lungs by chemokine production. PMID:25512083

  4. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma.

    PubMed

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-Ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-01-01

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3(-/-)) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3(-/-) mice compared with wild-type mice after OVA challenge, consistently with fewer CD4(+) T cells from AQP3(-/-) mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target. PMID:27165276

  5. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma

    PubMed Central

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S.; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-01-01

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3−/−) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3−/− mice compared with wild-type mice after OVA challenge, consistently with fewer CD4+ T cells from AQP3−/− mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target. PMID:27165276

  6. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor

    PubMed Central

    Malmhäll, Carina; Rådinger, Madeleine; Ramos-Ramirez, Patricia; Lu, You; Deák, Tünde; Semitekolou, Maria; Gaga, Mina; Sjöstrand, Margareta; Lötvall, Jan; Bossios, Apostolos

    2016-01-01

    Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. Methods A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Results Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Conclusion Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation. PMID:27513955

  7. Carbon Nanofibers Have IgE Adjuvant Capacity but Are Less Potent Than Nanotubes in Promoting Allergic Airway Responses

    PubMed Central

    Samuelsen, Mari; Marioara, Calin Daniel; Løvik, Martinus

    2013-01-01

    There is a growing concern for the possible health impact of nanoparticles. The main objective of this study was to investigate the allergy-promoting capacity of four different carbon nanofiber (CNF) samples in an injection and an airway mouse model of allergy. Secondly, the potency of the CNF was compared to the previously reported allergy-promoting capacity of carbon nanotubes (CNT) in the airway model. Ultrafine carbon black particles (ufCBP) were used as a positive control. Particles were given together with the allergen ovalbumin (OVA) either by subcutaneous injection into the footpad or intranasally to BALB/cA mice. After allergen booster, OVA-specific IgE, IgG1, and IgG2a in serum were measured. In the airway model, inflammation was determined as influx of inflammatory cells (eosinophils, neutrophils, lymphocytes, and macrophages) and by mediators (MCP-1 and TNF-α present in bronchoalveolar fluid (BALF)). CNF and CNT both increased OVA-specific IgE levels in the two models, but in the airway model, the CNT gave a significantly stronger IgE response than the CNF. Furthermore, the CNT and not the CNF promoted eosinophil lung inflammation. Our data therefore suggest that nanotube-associated properties are particularly potent in promoting allergic responses. PMID:24024193

  8. Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation

    PubMed Central

    Yang, Liyan; Cohn, Lauren; Zhang, Dong-Hong; Homer, Robert; Ray, Anuradha; Ray, Prabir

    1998-01-01

    The molecular mechanisms that contribute to an eosinophil-rich airway inflammation in asthma are unclear. A predominantly T helper 2 (Th2)-type cell response has been documented in allergic asthma. Here we show that mice deficient in the p50 subunit of nuclear factor (NF)- κB are incapable of mounting eosinophilic airway inflammation compared with wild-type mice. This deficiency was not due to a block in T cell priming or proliferation in the p50−/− mice, nor was it due to a defect in the expression of the cell adhesion molecules VCAM-1 and ICAM-1 that are required for the extravasation of eosinophils into the airways. The major defects in the p50−/− mice were the lack of production of the Th2 cytokine interleukin 5 and the chemokine eotaxin, which are crucial for proliferation and for differentiation and recruitment, respectively, of eosinophils into the asthmatic airway. Additionally, the p50−/− mice were deficient in the production of the chemokines macrophage inflammatory protein (MIP)-1α and MIP-1β that have been implicated in T cell recruitment to sites of inflammation. These results demonstrate a crucial role for NF-κB in vivo in the expression of important molecules that have been implicated in the pathogenesis of asthma. PMID:9802985

  9. Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma.

    PubMed

    Al-Harbi, Naif O; Nadeem, A; Al-Harbi, Mohamed M; Imam, F; Al-Shabanah, Othman A; Ahmad, Sheikh F; Sayed-Ahmed, Mohamed M; Bahashwan, Saleh A

    2015-05-01

    Oxidant-antioxidant imbalance plays an important role in repeated cycles of airway inflammation observed in asthma. It is when reactive oxygen species (ROS) overwhelm antioxidant defenses that a severe inflammatory state becomes apparent and may impact vasculature. Several studies have shown an association between airway inflammation and cardiovascular complications; however so far none has investigated the link between airway oxidative stress and systemic/vascular oxidative stress in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of vascular/systemic oxidant-antioxidant balance. Rats were sensitized intraperitoneally with ovalbumin (OVA) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with OVA. Rats were then assessed for airway and vascular inflammation, oxidative stress (ROS, lipid peroxides) and antioxidants measured as total antioxidant capacity (TAC) and thiol content. Challenge with OVA led to increased airway inflammation and oxidative stress with a concomitant increase in vascular inflammation and oxidative stress. Oxidative stress in the vasculature was significantly inhibited by antioxidant treatment, N-acetyl cysteine; whereas hydrogen peroxide (H2O2) inhalation worsened it. Therefore, our study shows that oxidative airway inflammation is associated with vascular/systemic oxidative stress which might predispose these patients to increased cardiovascular risk.

  10. The Ethanol Extract of Osmanthus fragrans Flowers Reduces Oxidative Stress and Allergic Airway Inflammation in an Animal Model

    PubMed Central

    Hung, Chien-Ya; Shi, Li-Shian; Wang, Jing-Yao; Tsai, Yu-Cheng; Ye, Yi-Ling

    2013-01-01

    The Osmanthus fragrans flower, a popular herb in Eastern countries, contains several antioxidant compounds. Ben Cao Gang Mu, traditional Chinese medical literature, describes the usefulness of these flowers for phlegm and stasis reduction, arrest of dysentery with blood in the bowel, and stomachache and diarrhea treatment. However, modern evidence regarding the therapeutic efficacy of these flowers is limited. This study was aimed at assessing the antioxidative effects of the ethanol extract of O. fragrans flowers (OFE) in vivo and evaluating its antioxidant maintenance and therapeutic effect on an allergic airway inflammation in mice. After OFE's oral administration to mice, the values obtained in the oxygen radical absorbance capacity assay as well as the glutathione concentration in the lungs and spleens of mice increased while thiobarbituric acid reactive substances decreased significantly, indicating OFE's significant in vivo antioxidant activity. OFE was also therapeutically efficacious in a mouse model of ovalbumin-induced allergic airway inflammation. Orally administered OFE suppressed ovalbumin-specific IgE production and inflammatory cell infiltration in the lung. Moreover, the antioxidative state of the mice improved. Thus, our findings confirm the ability of the O. fragrans flowers to reduce phlegm and suggest that OFE may be useful as an antiallergic agent. PMID:24386002

  11. Effects of prior oral exposure to combinations of environmental immunosuppressive agents on ovalbumin allergen-induced allergic airway inflammation in Balb/c mice.

    PubMed

    Fukuyama, Tomoki; Nishino, Risako; Kosaka, Tadashi; Watanabe, Yuko; Kurosawa, Yoshimi; Ueda, Hideo; Harada, Takanori

    2014-08-01

    Abstract Humans are exposed daily to multiple environmental chemicals in the atmosphere, in food, and in commercial products. Therefore, hazard identification and risk management must account for exposure to chemical mixtures. The objective of the study reported here was to investigate the effects of combinations of three well-known environmental immunotoxic chemicals - methoxychlor (MXC), an organochlorine compound; parathion (PARA), an organophosphate compound; and piperonyl butoxide (PBO), an agricultural insecticide synergist - by using a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Four-week-old Balb/c mice were exposed orally to either one or two of the environmental immunotoxic chemicals for five consecutive days, prior to intraperitoneal sensitization with OVA and an inhalation challenge. We assessed IgE levels in serum, B-cell counts, and cytokine production in hilar lymph nodes, and differential cell counts and levels of related chemokines in bronchoalveolar lavage fluid (BALF). Mice treated with MXC + PARA or PBO + MXC showed marked increases in serum IgE, IgE-positive B-cells and cytokines in lymph nodes, and differential cell counts and related chemokines in BALF compared with mice that received the vehicle control or the corresponding individual test substances. These results suggest that simultaneous exposure to multiple environmental chemicals aggravates allergic airway inflammation more than exposure to individual chemicals. It is expected that the results of this study will help others in their evaluation of immunotoxic combinational effects when conducting assessments of the safety of environmental/occupational chemicals.

  12. Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

    PubMed Central

    Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

    2015-01-01

    Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

  13. CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation

    PubMed Central

    Cruz, Fernanda F.; Borg, Zachary D.; Goodwin, Meagan; Coffey, Amy L.; Wagner, Darcy E.; Rocco, Patricia R.M.

    2016-01-01

    Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) or bone marrow-derived mesenchymal stromal cells (MSCs) reduces inflammation and airway hyperresponsiveness (AHR) in a murine model of Th2-mediated eosinophilic allergic airway inflammation. However, since BMDMCs are a heterogeneous population that includes MSCs, it is unclear whether the MSCs alone are responsible for the BMDMC effects. To determine which BMDMC population(s) is responsible for ameliorating AHR and lung inflammation in a model of mixed Th2-eosinophilic and Th17-neutrophilic allergic airway inflammation, reminiscent of severe clinical asthma, BMDMCs obtained from normal C57Bl/6 mice were serially depleted of CD45, CD34, CD11b, CD3, CD19, CD31, or Sca-1 positive cells. The different resulting cell populations were then assessed for ability to reduce lung inflammation and AHR in mixed Th2/Th17 allergic airway inflammation induced by mucosal sensitization to and challenge with Aspergillus hyphal extract (AHE) in syngeneic C56Bl/6 mice. BMDMCs depleted of either CD11b-positive (CD11b+) or Sca-1-positive (Sca-1+) cells were unable to ameliorate AHR or lung inflammation in this model. Depletion of the other cell types did not diminish the ameliorating effects of BMDMC administration. In conclusion, in the current model of allergic inflammation, CD11b+ cells (monocytes, macrophages, dendritic cells) and Sca-1+ cells (MSCs) are responsible for the beneficial effects of BMDMCs. Significance This study shows that bone marrow-derived mononuclear cells (BMDMCs) are as effective as bone marrow-derived mesenchymal stromal cells (MSCs) in ameliorating experimental asthma. It also demonstrates that not only MSCs present in the pool of BMDMCs are responsible for BMDMCs’ beneficial effects but also monocytes, which are the most important cell population to trigger these effects. All of this is in the setting of a clinically relevant model of severe allergic airways inflammation and thus

  14. RAPID COMMUNICATION IL-4 INDUCES IL-6 AND SIGNS OF ALLERGIC-TYPE INFLAMMATION IN THE NASAL AIRWAYS OF NONALLERGIC INDIVIDUALS

    EPA Science Inventory


    In addition to its more widely recognized role in promoting IgE synthesis, we speculate that interleukin-4 (IL-4) may modulate both allergic- and nonallergic-type inflammatory processes in the airway mucosa. We examined in vivo the effect of IL-4 on granulocyte and cytokine h...

  15. [Effect of heparin on airway goblet cell secretion in sensitized guinea pigs].

    PubMed

    Nakata, J; Tamaoki, J; Takeyama, K; Takeda, Y; Yamawaki, I; Kondo, M; Nagai, A

    1998-10-01

    Heparin and related proteoglycans are released from mast cells and possess anti-inflammatory and anti-complement activities. To elucidate whether heparin affects goblet cell secretion in asthmatic airways and, if so, what the mechanism of action is, we studied guinea pigs sensitized with ovalbumin (OVA) by determining the mucus score (MS) of tracheal goblet cells stained with Alcian blue and PAS. Inhalation of OVA caused a rapid decrease in MS in a dose-dependent manner, with the maximal decrease being from 545 +/- 26 to 192 +/- 35 (p < 0.001), indicating an increase in goblet cell mucus discharge. This effect was selectively inhibited by the histamine H2 receptor blockade with cimetidine. Prior inhalation of heparin inhibited OVA-induced goblet cell secretion in a dose-dependent fashion, but had no effect on histamine-induced goblet cell secretion. The OVA-induced histamine release from the tracheal tissue was likewise inhibited by heparin. These results suggest that allergic challenge stimulates airway goblet cell secretion mainly through the release of histamine and the concomitant activation of histamine H2 receptors on goblet cells, and that heparin protects against this effect by inhibiting the histamine release from mast cells.

  16. Therapy with resveratrol attenuates obesity-associated allergic airway inflammation in mice.

    PubMed

    André, Diana Majolli; Calixto, Marina Ciarallo; Sollon, Carolina; Alexandre, Eduardo Costa; Leiria, Luiz O; Tobar, Natalia; Anhê, Gabriel Forato; Antunes, Edson

    2016-09-01

    Obesity and insulin resistance have been associated with deterioration in asthma outcomes. High oxidative stress and deficient activation of AMP-activated protein kinase (AMPK) have emerged as important regulators linking insulin resistance and inflammation. This study aimed to evaluate the effects of resveratrol on obesity-associated allergic pulmonary inflammation. Male C57/Bl6 mice fed with high-fat diet to induce obesity (obese group) or standard-chow diet (lean group) were treated or not with resveratrol (100mg/kg/day, two weeks). Mice were sensitized and challenged with ovalbumin (OVA). At 48h thereafter, bronchoalveolar lavage fluid was performed, and lungs collected for morphological studies and Western blot analysis. Treatment of obese mice with resveratrol significantly reduced hyperglycemia and insulin resistance, as well as the body measures (body mass, fat mass, % fat, and body area). OVA-challenge promoted a higher increase in pulmonary eosinophil infiltration in obese compared with lean mice, which was nearly abrogated by resveratrol treatment. Resveratrol markedly increased the phosphorylated AMPK expression in lung tissues of obese compared with lean mice. Resveratrol reduced the p47phox expression and reactive-oxygen species (ROS) production, and elevated the superoxide dismutase (SOD) levels in lung tissues of obese mice. The increased pulmonary levels of TNF-α and inducible nitric oxide synthase (iNOS) in obese mice were also normalized after resveratrol treatment. In lean mice, resveratrol failed to affect the levels of fasting glucose, p47phox, ROS levels, TNF-α, iNOS and phosphorylated AMPK. Resveratrol exhibits protective effects in obesity-associated lung inflammation that is accompanied by local AMPK activation and antioxidant property. PMID:27344038

  17. [Histamine H₁ receptor gene as an allergic diseases-sensitive gene and its impact on therapeutics for allergic diseases].

    PubMed

    Mizuguchi, Hiroyuki; Kitamura, Yoshiaki; Kondo, Yuto; Kuroda, Wakana; Yoshida, Haruka; Miyamoto, Yuko; Hattori, Masashi; Takeda, Noriaki; Fukui, Hiroyuki

    2011-02-01

    Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H₁ receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene.

  18. Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation

    PubMed Central

    Ooi, Aik T; Ram, Sonal; Kuo, Alan; Gilbert, Jennifer L; Yan, Weihong; Pellegrini, Matteo; Nickerson, Derek W; Chatila, Talal A; Gomperts, Brigitte N

    2012-01-01

    Epigenetic changes have been implicated in the pathogenesis of asthma. We sought to determine if IL13, a key cytokine in airway inflammation and remodeling, induced epigenetic DNA methylation and miRNAs expression changes in the airways in conjunction with its transcriptional gene regulation. Inducible expression of an IL13 transgene in the airways resulted in significant changes in DNA methylation in 177 genes, most of which were associated with the IL13 transcriptional signature in the airways. A large number of genes whose expression was induced by IL13 were found to have decreased methylation, including those involved in tissue remodeling (Olr1), leukocyte influx (Cxcl3, Cxcl5, CSFr2b), and the Th2 response (C3ar1, Chi3l4). Reciprocally, some genes whose expression was suppressed were found to have increased methylation (e.g. Itga8). In addition, miRNAs were identified with targets for lung development and Wnt signaling, amongst others. These results indicate that IL13 confers an epigenetic methylation and miRNA signature that accompanies its transcriptional program in the airways, which may play a critical role in airway inflammation and remodeling. PMID:22611474

  19. [Recent advances in DNA vaccines against allergic airway disease: a review].

    PubMed

    Ou, Jin; Xu, Yu; Shi, Wendan

    2013-12-01

    DNA vaccine is used in infectious diseases initially, and later is applied in neoplastic diseases, allergic diseases and other fields with the further understanding of DNA vaccine and the development of genetic engineering. DNA vaccine transfers the genes encoding exogenous antigens to plasmid vector and then is introduced into organism. It controls the antigen proteins synthesis, thus induces specific humoral and cellular immune responses. So it has a broad application prospect in allergic diseases. Compared with the traditional protein vaccines used in specific immunotherapy, DNA vaccine has many advantages, including high purity and specificity, and improvement of patients' compliance etc. However, there are still two unsolved problems. First, the transfection rate of unmodified naked DNA plasmid is not high, Second, it's difficult to induce ideal immune response. In this study, we will review the progress of DNA vaccine applications in respiratory allergic diseases and its various optimization strategies.

  20. Effects of SO/sub 2/ exposure on allergic sensitization in the guinea pig

    SciTech Connect

    Riedel, F.; Kraemer, M.S.; Scheibenbogen, C.; Rieger, C.H.

    1988-10-01

    The effect of sulfur dioxide (SO2) exposure on local bronchial sensitization to inhaled antigen was studied in the guinea pig. Exposure to SO2 (0.1 to 16.6 ppm) was performed in a 20 L exposure chamber for 8 hours on 5 consecutive days, while temperature, moisture, and concentration of SO2 were monitored and kept constant. SO2 concentrations were measured hourly by Schiff's reaction. On the last 3 days, SO2 exposure was followed by inhalation of nebulized ovalbumin (OA) for 45 minutes. One week later, specific bronchial provocation with inhaled OA (0.1%) followed by plethysmographic measurements of airway obstruction were performed every 2 days during a 2-week period. Specific antibodies against OA were measured in serum and bronchoalveolar fluid by a direct enzyme immunoassay. The SO2-exposed group (N = 17) demonstrated 67% to 100% positive bronchial reactions to inhaled OA, depending on the concentration of SO2, whereas the control group without previous SO2 exposure (N = 14) demonstrated bronchial reactions in only one animal (7%: p less than 0.05). The degree of bronchial obstruction was significantly higher in the exposed group, compared to the control group, for all SO2 concentrations (p less than 0.05). OA-specific antibodies in serum and bronchoalveolar fluid increased in SO2-exposed groups significantly, compared to the control group (p less than 0.05). It is concluded from these results that exposure to SO2 in low and medium concentrations can facilitate local allergic sensitization in the guinea pig.

  1. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    SciTech Connect

    Chou, Debbie L.; Gerriets, Joan E.; Schelegle, Edward S.; Hyde, Dallas M.; Miller, Lisa A.

    2011-12-15

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: Black-Right-Pointing-Pointer Ozone can modulate the localization of eosinophils in infant allergic airways. Black-Right-Pointing-Pointer Expression of eotaxins within the lung is affected by ozone and allergen exposure. Black-Right-Pointing-Pointer CCL24 induction by

  2. SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES

    SciTech Connect

    Diaz-Sanchez, David

    2000-08-20

    Most studies of the health effects of diesel exhaust have focused on the controversial issue of its role in cancer. However, recently the role of combustion products such as diesel exhaust particles (DEP) in modulating the immune response has garnered much attention. In particular the effect of DEP on allergic and asthmatic diseases has been the focus of many studies. A link between industrialization and allergic disease has long been presumed. Indeed, only 50 years after the first recorded reported case of allergy in 1819, Charles Blackely wrote that the ''hay-fever epidemic'' was associated with the movement of people from the country into the cities. Ishizaki et al. (1987) found that people in Japan living on busy roads lined with cedar trees have more allergies to cedar than residents living on similar streets with much less traffic. Since that time other epidemiological studies have reported similar findings. Kramer, et al., showed that hay fever is greater in residential areas with heavy truck traffic, while Weiland, et al., reported that allergic symptoms correlate with the distance of residences to roads with heavy traffic.

  3. Animal Models of Allergic Airways Disease: Where Are We and Where to Next?

    PubMed Central

    Chapman, David G.; Tully, Jane E.; Nolin, James D.; Jansen-Heininger, Yvonne M; Irvin, Charles G.

    2014-01-01

    In a complex inflammatory airways disease such as asthma, abnormalities in a plethora of molecular and cellular pathways ultimately culminate in characteristic impairments in respiratory function. The ability to study disease pathophysiology in the setting of a functioning immune and respiratory system therefore makes mouse models an invaluable tool in translational research. Despite the vast understanding of inflammatory airways diseases gained from mouse models to date, concern over the validity of mouse models continues to grow. Therefore the aim of this review is two-fold; firstly, to evaluate mouse models of asthma in light of current clinical definitions, and secondly, to provide a framework by which mouse models can be continually refined so that they continue to stand at the forefront of translational science. Indeed, it is in viewing mouse models as a continual work in progress that we will be able to target our research to those patient populations in whom current therapies are insufficient. PMID:25043224

  4. Effects of corticosteroid treatment on airway inflammation, mechanics, and hyperpolarized ³He magnetic resonance imaging in an allergic mouse model.

    PubMed

    Thomas, Abraham C; Kaushik, S Sivaram; Nouls, John; Potts, Erin N; Slipetz, Deborah M; Foster, W Michael; Driehuys, Bastiaan

    2012-05-01

    The purpose of this study was to assess the effects of corticosteroid therapy on a murine model of allergic asthma using hyperpolarized (3)He magnetic resonance imaging (MRI) and respiratory mechanics measurements before, during, and after methacholine (MCh) challenge. Three groups of mice were prepared, consisting of ovalbumin sensitized/ovalbumin challenged (Ova/Ova, n = 5), Ova/Ova challenged but treated with the corticosteroid dexamethasone (Ova/Ova+Dex, n = 3), and ovalbumin-sensitized/saline-challenged (Ova/PBS, n = 4) control animals. All mice underwent baseline 3D (3)He MRI, then received a MCh challenge while 10 2D (3)He MR images were acquired for 2 min, followed by post-MCh 3D (3)He MRI. Identically treated groups underwent respiratory mechanics evaluation (n = 4/group) and inflammatory cell counts (n = 4/group). Ova/Ova animals exhibited predominantly large whole lobar defects at baseline, with significantly higher ventilation defect percentage (VDP = 19 ± 4%) than Ova/PBS (+2 ± 1%, P = 0.01) animals. Such baseline defects were suppressed by dexamethasone (0%, P = 0.009). In the Ova/Ova group, MCh challenge increased VDP on both 2D (+30 ± 8%) and 3D MRI scans (+14 ± 2%). MCh-induced VDP changes were diminished in Ova/Ova+Dex animals on both 2D (+21 ± 9%, P = 0.63) and 3D scans (+7 ± 2%, P = 0.11) and also in Ova/PBS animals on 2D (+6 ± 3%, P = 0.07) and 3D (+4 ± 1%, P = 0.01) scans. Because MCh challenge caused near complete cessation of ventilation in four of five Ova/Ova animals, even as large airways remained patent, this implies that small airway (<188 μm) obstruction predominates in this model. This corresponds with respiratory mechanics observations that MCh challenge significantly increases elastance and tissue damping but only modestly affects Newtonian airway resistance. PMID:22241062

  5. Tracking of Inhaled Near-Infrared Fluorescent Nanoparticles in Lungs of SKH-1 Mice with Allergic Airway Inflammation.

    PubMed

    Markus, M Andrea; Napp, Joanna; Behnke, Thomas; Mitkovski, Miso; Monecke, Sebastian; Dullin, Christian; Kilfeather, Stephen; Dressel, Ralf; Resch-Genger, Ute; Alves, Frauke

    2015-12-22

    Molecular imaging of inflammatory lung diseases, such as asthma, has been limited to date. The recruitment of innate immune cells to the airways is central to the inflammation process. This study exploits these cells for imaging purposes within the lung, using inhaled polystyrene nanoparticles loaded with the near-infrared fluorescence dye Itrybe (Itrybe-NPs). By means of in vivo and ex vivo fluorescence reflectance imaging of an ovalbumin-based allergic airway inflammation (AAI) model in hairless SKH-1 mice, we show that subsequent to intranasal application of Itrybe-NPs, AAI lungs display fluorescence intensities significantly higher than those in lungs of control mice for at least 24 h. Ex vivo immunofluorescence analysis of lung tissue demonstrates the uptake of Itrybe-NPs predominantly by CD68(+)CD11c(+)ECF-L(+)MHCII(low) cells, identifying them as alveolar M2 macrophages in the peribronchial and alveolar areas. The in vivo results were validated by confocal microscopy, overlapping tile analysis, and flow cytometry, showing an amount of Itrybe-NP-containing macrophages in lungs of AAI mice significantly larger than that in controls. A small percentage of NP-containing cells were identified as dendritic cells. Flow cytometry of tracheobronchial lymph nodes showed that Itrybe-NPs were negligible in lung draining lymph nodes 24 h after inhalation. This imaging approach may advance preclinical monitoring of AAI in vivo over time and aid the investigation of the role that macrophages play during lung inflammation. Furthermore, it allows for tracking of inhaled nanoparticles and can hence be utilized for studies of the fate of potential new nanotherapeutics.

  6. Maternal diet during lactation and allergic sensitization in the offspring at age of 5.

    PubMed

    Nwaru, Bright I; Erkkola, Maijaliisa; Ahonen, Suvi; Kaila, Minna; Lumia, Mirka; Prasad, Marianne; Haapala, Anna-Maija; Kronberg-Kippilä, Carina; Veijola, Riitta; Ilonen, Jorma; Simell, Olli; Knip, Mikael; Virtanen, Suvi M

    2011-05-01

    The objective of this study was to examine the effect of maternal dietary intake during lactation on allergic sensitization at the age of 5 in children carrying HLA-DQB1-conferred susceptibility to type 1 diabetes. We analyzed data for 652 consecutively born children with complete information on maternal diet and allergen-specific immunoglobulin E (IgE) measurements who are participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition and allergy study. Analysis was performed using logistic regression. In models that included the significant uncorrelated dietary variables, maternal intake of butters and saturated fatty acids was associated with increased risk, while margarine was associated with a decreased risk, of sensitization to wheat allergen in the offspring. Maternal intake of potatoes, milks, and margarine and low-fat spreads were associated with decreased risk of sensitization to birch allergen. On the other hand, intake of potatoes decreased the risk, while vitamin C and eggs increased the risk, of cat allergic sensitization. Maternal intake of butters and saturated fatty acids during lactation may increase the risk, while margarines may decrease the risk, of sensitization to wheat allergen in the offspring. Maternal intake of potatoes, milks, and margarines may decrease the risk of sensitization to birch allergen. On the other hand, intake of potatoes may decrease the risk, while vitamin C and eggs may increase the risk, of cat allergic sensitization. These effects may persist regardless of maternal or parental allergic status.

  7. Intranasal trigeminal sensitivity in subjects with allergic rhinitis.

    PubMed

    Doerfler, H; Hummel, T; Klimek, L; Kobal, G

    2006-01-01

    Trigeminal nerve endings of the human nasal mucosa are activated by chemical, physical or thermal stimuli. Activation of these A(delta) and C fibers can be quantified through the recording of chemo-somatosensory event-related potentials (ERP). The aim of this study was to investigate whether allergy-related activation of trigeminal nerve endings leads to changes in their responsiveness to intranasal trigeminal stimulation. Gaseous carbon dioxide (CO(2)) stimuli were applied in three sessions (baseline, after NaCl solution and after allergen application) to the nasal mucosa of 13 subjects with allergic rhinitis. Chemo-somatosensory ERP were recorded, and subjects rated the intensity of rhinitis symptoms. Administration of allergen produced a significant shortening of chemo-somatosensory ERP peak latencies P1 and N1. Observed changes of latencies were in line with rhinitis symptoms subjects indicated during the session. In addition, there was a negative relation between the general symptom score and ERP peak latencies, obtained both at baseline and after allergen exposure. In conclusion, it is hypothesized that in patients suffering from allergic rhinitis, nasal itching and sneezing after allergen exposure are, at least in part, clinical correlates of the activation of trigeminal nerve endings due to local inflammatory mechanisms. The correlations between ERP latencies and the patients' symptoms indicate that ERP latencies may possess a predictive value of the subjects' responsiveness to allergens.

  8. Epithelial barrier function: at the frontline of asthma immunology and allergic airway inflammation

    PubMed Central

    Georas, Steve N.; Rezaee, Fariba

    2014-01-01

    Airway epithelial cells form a barrier to the outside world, and are at the frontline of mucosal immunity. Epithelial apical junctional complexes are multi-protein subunits that promote cell-cell adhesion and barrier integrity. Recent studies in the skin and GI tract suggest that disruption of cell-cell junctions is required to initiate epithelial immune responses, but how this applies to mucosal immunity in the lung is not clear. Increasing evidence indicates that defective epithelial barrier function is a feature of airway inflammation in asthma. One challenge in this area is that barrier function and junctional integrity are difficult to study in the intact lung, but innovative approaches should provide new knowledge in this area in the near future. In this article, we review the structure and function of epithelial apical junctional complexes, emphasizing how regulation of the epithelial barrier impacts innate and adaptive immunity. We discuss why defective epithelial barrier function may be linked to Th2 polarization in asthma, and propose a rheostat model of barrier dysfunction that implicates the size of inhaled allergen particles as an important factor influencing adaptive immunity. PMID:25085341

  9. T cell derived IL-10 is dispensable for tolerance induction in a murine model of allergic airway inflammation.

    PubMed

    Kunz, Stefanie; Dolch, Anja; Surianarayanan, Sangeetha; Dorn, Britta; Bewersdorff, Mayte; Alessandrini, Francesca; Behrendt, Rayk; Karp, Christopher L; Muller, Werner; Martin, Stefan F; Roers, Axel; Jakob, Thilo

    2016-08-01

    Regulatory mechanisms initiated by allergen-specific immunotherapy are mainly attributed to T cell derived IL-10. However, it has not been shown that T cell derived IL-10 is required for successful tolerance induction (TI). Here, we analyze cellular sources and the functional relevance of cell type specific IL-10 during TI in a murine model of allergic airway inflammation. While TI was effective in IL-10 competent mice, neutralizing IL-10 prior to tolerogenic treatment completely abrogated the beneficial effects. Cellular sources of IL-10 during TI were identified by using transcriptional reporter mice as T cells, B cells, and to a lesser extent DCs. Interestingly, TI was still effective in mice with T cell, B cell, B and T cell, or DC-specific IL-10 deficiency. In contrast, TI was not possible in mice lacking IL-10 in all hematopoetic cells, while it was effective in bone marrow (BM) chimera that lacked IL-10 only in nonhematopoetic cells. Taken together, allergen-specific tolerance depends on IL-10 from hematopoetic sources. The beneficial effects of allergen-specific immunotherapy cannot solely be attributed to IL-10 from T cells, B cells, or even DCs, suggesting a high degree of cellular redundancy in IL-10-mediated tolerance. PMID:27287239

  10. Effects of environmental pollutants on airways, allergic inflammation, and the immune response.

    PubMed

    Handzel, Z T

    2000-01-01

    Particulate and gaseous air pollutants are capable of damaging the airway epithelial lining and of shifting the local immune balance, thereby facilitating the induction of persistent inflammation. Epidemiological studies are inconclusive regarding whether air pollution increases the incidence of asthma and chronic bronchitis in the population. Clearly, environmental pollution can, however, precipitate attacks and emergency-room admissions in those already suffering from such conditions. The catastrophic potential of airborne pollution was demonstrated in the 1960s and 1970s, when inverted atmospheric pressure conditions trapped smog over cities on the Eastern coast of the United States and over Europe. This smog resulted in thousands of hospital admissions and dozens of deaths. With the general rise in the incidence of atopy and asthma in the Western population, it is of major public health interest to reduce, as much as possible, the exposure of such populations to anthropogenic and natural sources of pollution. PMID:11048334

  11. Reversal of established CD4+ type 2 T helper-mediated allergic airway inflammation and eosinophilia by therapeutic treatment with DNA vaccines limits progression towards chronic inflammation and remodelling

    PubMed Central

    Jarman, Elizabeth R; Lamb, Jonathan R

    2004-01-01

    Immunostimulatory DNA-based vaccines can prevent the induction of CD4+ type 2 T helper (Th2) cell-mediated airway inflammation in experimental models, when administered before or at the time of allergen exposure. Here we demonstrate their efficacy in limiting the progression of an established response to chronic pulmonary inflammation and airway remodelling on subsequent allergen challenge. Mice exhibiting Th2-mediated airway inflammation induced following sensitization and challenge with group 1 allergen derived from Dermatophagoides pteronyssinus group species (Der p 1), a major allergen of house dust mite, were treated with pDNA vaccines. Their airways were rechallenged and the extent of inflammation assessed. In plasma DNA (pDNA)-vaccinated mice, infiltration of inflammatory cells, goblet cell hyperplasia and mucus production were reduced and subepithelial fibrosis attenuated. The reduction in eosinophil numbers correlated with a fall in levels of the profibrotic mediator transforming growth factor (TGF)-β1 in bronchoalveolar lavage (BAL) and lung tissue. In addition to lung epithelial cells and resident alveolar macrophages, infiltrating eosinophils, the principle inflammatory cells recruited following allergen exposure, were a major source of TGF-β1. Protection, conferred irrespective of the specificity of the pDNA construct, did not correlate with a sustained increase in systemic interferon (IFN)-γ production but in a reduction in levels of the Th2 pro-inflammatory cytokines. Notably, there was a reduction in levels of interleukin (IL)-5 and IL-13 produced by systemic Der p 1 reactive CD4+ Th2 cells on in vitro stimulation as well as in IL-4 and IL-5 levels in BAL fluid. These data suggest that suppression of CD4+ Th2-mediated inflammation and eosinophilia were sufficient to attenuate progression towards airway remodelling. Immunostimulatory DNA may therefore have a therapeutic application in treatment of established allergic asthma in patients. PMID

  12. VARIATIONS IN PEAK EXPIRATORY FLOW MEASUREMENTS ASSOCIATED TO AIR POLLUTION AND ALLERGIC SENSITIZATION IN CHILDREN IN SAO PAULO, BRAZIL

    PubMed Central

    de M Correia-Deur, Joya Emilie; Claudio, Luz; Imazawa, Alice Takimoto; Eluf-Neto, Jose

    2012-01-01

    Background In the last 20 years, there has been an increase in the incidence of allergic respiratory diseases worldwide and exposure to air pollution has been discussed as one of the factors associated with this increase. The objective of this study was to investigate the effects of air pollution on peak expiratory flow (PEF) and FEV1 in children with and without allergic sensitization. Methods Ninety-six children were followed from April to July, 2004 with spirometry measurements. They were tested for allergic sensitization (IgE, skin prick test, eosinophilia) and asked about allergic symptoms. Air pollution, temperature and relative humidity data were available. Results Decrements in PEF were observed with previous 24-h average exposure to air pollution, as well as with 3 to 10 day average exposure and were associated mainly with PM10, NO2 and O3. in all three categories of allergic sensitization. Even though allergic sensitized children tended to present larger decrements in the PEF measurements they were not statistically different from the non-allergic sensitized. Decrements in FEV1 were observed mainly with previous 24-h average exposure and 3-day moving average. Conclusions Decrements in PEF associated with air pollution were observed in children independent from their allergic sensitization status. Their daily exposure to air pollution can be responsible for a chronic inflammatory process that might impair their lung growth and later their lung function in adulthood. PMID:22544523

  13. [Allergens-induced sensitization alters airway epithelial adhesion molecules expression in mice].

    PubMed

    Zeng, Dan; Tan, Mei-Ling; Xiang, Yang; Qin, Xiao-Qun; Zhu, Li-Ming; Dai, Ai-Guo

    2015-12-25

    To explore the relationship between the epithelial adhesion molecules and immune responses of airway epithelium, we observed the expression of integrin β4 and intercellular adhesion molecule-1 (ICAM-1) in the mice airway epithelium after sensitization with allergens. BALB/c mice were sensitized with intraperitoneal injection of ovalbumin (OVA) or house dust mite (HDM) and then developed airway hyper-responsiveness as determined by barometric whole-body plethysmography. Both OVA and HDM sensitization led to increases of the number of peripheral leukocytes as well as inflammatory cells infiltration in lungs. OVA sensitized mice showed more severe inflammatory cells infiltration than HDM sensitized mice. Immunohistochemistry analysis of mice lung tissues revealed that sensitization with both allergens also led to a decrease of integrin β4 expression and an increase of ICAM-1 expression in airway epithelia. OVA sensitized mice showed a more significant increase of ICAM-1 expression compared with HDM sensitized mice. siRNA mediated silencing of integrin β4 gene in 16HBE cells resulted in an up-regulation of ICAM-1 expression. Our results indicate a possible role of airway epithelial adhesion molecules in allergen-induced airway immune responses. PMID:26701635

  14. Textile dye allergic contact dermatitis following paraphenylenediamine sensitization from a temporary tattoo.

    PubMed

    Saunders, Helen; O'Brien, Timothy; Nixon, Rosemary

    2004-11-01

    Textile dye allergy is frequently caused by azo dyes, which can cross-react with structurally similar compounds, including paraphenylenediamine. A case of allergic contact dermatitis to azo textile dyes, presenting principally as a sock dermatitis, is presented. The patient also gave a history of an episode of scalp dermatitis consistent with contact allergy to paraphenylenediamine in hair dye. It is proposed that paraphenylenediamine sensitization from a temporary skin tattoo may have been the primary sensitizing event for these reactions. PMID:15527435

  15. Textile dye allergic contact dermatitis following paraphenylenediamine sensitization from a temporary tattoo.

    PubMed

    Saunders, Helen; O'Brien, Timothy; Nixon, Rosemary

    2004-11-01

    Textile dye allergy is frequently caused by azo dyes, which can cross-react with structurally similar compounds, including paraphenylenediamine. A case of allergic contact dermatitis to azo textile dyes, presenting principally as a sock dermatitis, is presented. The patient also gave a history of an episode of scalp dermatitis consistent with contact allergy to paraphenylenediamine in hair dye. It is proposed that paraphenylenediamine sensitization from a temporary skin tattoo may have been the primary sensitizing event for these reactions.

  16. Airway reactivity to inhaled spasmogens 18-24 h after antigen-challenge in sensitized anaesthetized guinea-pigs.

    PubMed

    Johnson, A; Broadley, K J

    1997-11-01

    The anaesthetized allergic guinea-pig was used to assess changes in airway reactivity to four different inhaled spasmogens: methacholine, 5-hydroxytryptamine (5-HT), histamine and the thromboxane A2 mimetic, 9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha (U-46619). Reactivity was determined 18 to 24 h after challenge of ovalbumin-sensitized guinea-pigs with inhaled ovalbumin. This time coincides with the appearance of a late-phase bronchoconstriction in these animals. Sensitivity to the spasmogen was assessed from the concentration-response curve for the increase in pulmonary inflation pressure (PIP) in ovalbumin- and saline-challenged sensitized animals. When methacholine, 5-HT or histamine were the spasmogens there was no hyper-reactivity. The geometric mean EC50 values (i.e. the concentrations inducing half the maximum effect) obtained from the dose-response curves for methacholine (73 (42-129) and 94 (66-134) micrograms mL-1), 5-HT (1.5 (0.81-3.03) and 1.1 (0.51-2.24 micrograms mL-1) and histamine (39 (21-75) and 72 (32-162) micrograms mL-1) did not differ significantly (P > 0.05) between saline- and ovalbumin-challenged animals, respectively. However, when U-46619 was the spasmogen, ovalbumin-induced airway hyper-reactivity was observed as a leftwards shift of the concentration-response curve and the EC50 value for ovalbumin-challenged animals (8.1 (5.1-13) ng mL-1) was significantly (P < 0.05) less than the value for control animals (39 (21-75) ng mL-1). Our findings suggest that airway hyper-reactivity is not 'non-specific', but instead depends on the chosen spasmogen. The absence of hyper-reactivity with certain spasmogens was not a result of poor delivery, because all spasmogens caused a bronchoconstriction by the inhaled route. It was also not associated with the model because ozone has been shown to induce hyper-reactivity to inhaled methacholine and 5-HT. Because airway hyper-reactivity to both inhaled histamine and agonists at muscarinic

  17. Allergen Microarray Indicates Pooideae Sensitization in Brazilian Grass Pollen Allergic Patients

    PubMed Central

    Moreira, Priscila Ferreira de Sousa; Gangl, Katharina; Vieira, Francisco de Assis Machado; Ynoue, Leandro Hideki; Linhart, Birgit; Flicker, Sabine; Fiebig, Helmut; Swoboda, Ines; Focke-Tejkl, Margarete; Taketomi, Ernesto Akio; Valenta, Rudolf; Niederberger, Verena

    2015-01-01

    Background Grass pollen, in particular from Lolium multiflorum is a major allergen source in temperate climate zones of Southern Brazil. The IgE sensitization profile of Brazilian grass pollen allergic patients to individual allergen molecules has not been analyzed yet. Objective To analyze the IgE sensitization profile of a Brazilian grass pollen allergic population using individual allergen molecules. Methods We analyzed sera from 78 grass pollen allergic patients for the presence of IgE antibodies specific for 103 purified micro-arrayed natural and recombinant allergens by chip technology. IgE-ELISA inhibition experiments with Lolium multiflorum, Phleum pratense extracts and a recombinant fusion protein consisting of Phl p 1, Phl p 2, Phl p 5 and Phl p 6 were performed to investigate cross-reactivities. Results Within the Brazilian grass pollen allergic patients, the most frequently recognized allergens were Phl p 1 (95%), Phl p 5 (82%), Phl p 2 (76%) followed by Phl p 4 (64%), Phl p 6 (45%), Phl p 11 (18%) and Phl p 12 (18%). Most patients were sensitized only to grass pollen allergens but not to allergens from other sources. A high degree of IgE cross-reactivity between Phleum pratense, Lolium multiflorum and the recombinant timothy grass fusion protein was found. Conclusions Component-resolved analysis of sera from Brazilian grass pollen allergic patients reveals an IgE recognition profile compatible with a typical Pooideae sensitization. The high degree of cross-reactivity between Phleum pratense and Lolium multiflorum allergens suggests that diagnosis and immunotherapy can be achieved with timothy grass pollen allergens in the studied population. PMID:26067084

  18. Nitrogen Dioxide and Allergic Sensitization in the 2005–2006 National Health and Nutrition Examination Survey

    PubMed Central

    Weir, Charles H.; Yeatts, Karin B.; Sarnat, Jeremy A.; Vizuete, William; Salo, Päivi M.; Jaramillo, Renee; Cohn, Richard D.; Chu, Haitao; Zeldin, Darryl C.; London, Stephanie J.

    2014-01-01

    Background Allergic sensitization is a risk factor for asthma and allergic diseases. The relationship between ambient air pollution and allergic sensitization is unclear. Objective To investigate the relationship between ambient air pollution and allergic sensitization in a nationally representative sample of the US population. Methods We linked annual average concentrations of nitrogen dioxide (NO2), particulate matter ≤ 10 µm (PM10), particulate matter ≤ 2.5 µm (PM25), and summer concentrations of ozone (O3), to allergen-specific immunoglobulin E (IgE) data for participants in the 2005–2006 National Health and Nutrition Examination Survey (NHANES). In addition to the monitor-based air pollution estimates, we used the Community Multiscale Air Quality (CMAQ) model to increase the representation of rural participants in our sample. Logistic regression with population-based sampling weights was used to calculate adjusted prevalence odds ratios per 10 ppb increase in O3 and NO2, per 10 µg/m3 increase in PM10, and per 5 µg/m3 increase in PM2.5 adjusting for race, gender, age, socioeconomic status, smoking, and urban/rural status. Results Using CMAQ data, increased levels of NO2 were associated with positive IgE to any (OR 1.15, 95% CI 1.04, 1.27), inhalant (OR 1.17, 95% CI 1.02, 1.33), and outdoor (OR 1.16, 95% CI 1.03, 1.31) allergens. Higher PM2.5 levels were associated with positivity to indoor allergen-specific IgE (OR 1.24, 95% CI 1.13, 1.36). Effect estimates were similar using monitored data. Conclusions Increased ambient NO2 was consistently associated with increased prevalence of allergic sensitization. PMID:24045117

  19. 167 Allergen Sensitization in Children with Allergic Rhinitis and Asthma in Guatemala

    PubMed Central

    Rigalt, Ann Michelle; Maselli, Juan Pablo; Alvarado, Ninotchka; Carpio, Paola; Chur, Víctor; Mayén, Patricia; Morán, Edgar; Pinto, Mario; Rodríguez, Juan Manuel

    2012-01-01

    Background There are no previous studies published reporting allergen sensitizations in the population of most Central American countries, including Guatemala. There are many types of climates in different regions, with variable altitude, humidity, etc. The purpose of this study was to determine the most common allergen sensitizations in children with Allergic Rhinitis and Asthma in 4 different regions. Methods The study was performed on 461 children aged 5 to 15 years, from 4 different regions in Guatemala. A questionnaire was given to record information regarding family history of atopic disease and symptoms of Rhinitis and Asthma. The diagnosis was made in the presence of at least 3 symptoms of each disease. Scratch testing was performed using a commercially available device and a panel of 8 allergen extracts: Cypress Arizona, Dog, Cat, Dermatophagoides farinae and pteronyssinus, Cockroach Mix, Mold Mix and Bermuda grass. Results Patient average age was 8.3 years, 55% male and 45% female. Patient distribution by region was 35% from Huehuetenango, 29% Chiquimula, 18% Mazatenango and 18% Quetzaltenango. Family history of allergic rhinitis was present in 46% of patients, asthma in 51% and atopic dermatitis in 33%. The most common diagnosis was rhinitis in 86% of patients, 52% had asthma and 43%, both rhinitis and asthma. 98% had a positive Histamine Control and all a Negative Saline Control. 36% of patients had no allergy sensitization to allergens tested and 64% showed positive skin tests. The most frequent allergic sensitization was to Dermatophagoides pteronyssinus (44%) and farinae (43%), followed by Cockroach (28%). We also found less frequently, positive skin tests to grass (14%), Cat (14%), Mold (10%), Dog (8%) and Cypress (6%). The regions with higher dust mite sensitization were Quetzaltenango (51–55%) and Huehuetenango (45–51%). Conclusions The most common allergen sensitizations in children with allergic rhinitis and asthma in Guatemala are dust

  20. Subcutaneous Allergic Sensitization to Protease Allergen Is Dependent on Mast Cells but Not IL-33: Distinct Mechanisms between Subcutaneous and Intranasal Routes.

    PubMed

    Kamijo, Seiji; Suzuki, Mayu; Hara, Mutsuko; Shimura, Sakiko; Ochi, Hirono; Maruyama, Natsuko; Matsuda, Akira; Saito, Hirohisa; Nakae, Susumu; Suto, Hajime; Ichikawa, Saori; Ikeda, Shigaku; Ogawa, Hideoki; Okumura, Ko; Takai, Toshiro

    2016-05-01

    Protease activity of papain, a plant-derived occupational allergen homologous to mite major allergens, is essential to IgE/IgG1 production and lung eosinophilia induced by intranasal papain administration in mice, and IL-33 contributes to these responses. In this work, we investigate skin and Ab responses induced by s.c. papain administration into ear lobes and responses induced by subsequent airway challenge with papain. Subcutaneous papain injection induced swelling associated with increased epidermal thickness, dermal inflammation, serum IgE/IgG1 responses, and Th2 cytokine production in draining lymph node cells restimulated in vitro. These responses were markedly less upon s.c. administration of protease inhibitor-treated papain. Results obtained by using mast cell-deficient mice and reconstitution of tissue mast cells suggested the contribution of mast cells to papain-specific IgE/IgG1 responses and eosinophil infiltration. The responses were equivalent between wild-type and IL-33(-/-) mice. After the subsequent airway challenge, the s.c. presensitized wild-type mice showed more severe lung eosinophilia than those without the presensitization. The presensitized IL-33(-/-) mice showed modest lung eosinophilia, which was absent without the presensitization, but its severity and IgE boost by the airway challenge were markedly less than the presensitized wild-type mice, in which protease activity of inhaled papain contributed to the responses. The results suggest that mechanisms for the protease-dependent sensitization differ between skin and airway and that cooperation of mast cell-dependent, IL-33-independent initial sensitization via skin and protease-induced, IL-33-mediated mechanism in re-exposure via airway to protease allergens maximizes the magnitude of the transition from skin inflammation to asthma in natural history of progression of allergic diseases. PMID:27001956

  1. A risk assessment process for allergic contact sensitization.

    PubMed

    Robinson, M K; Stotts, J; Danneman, P J; Nusair, T L; Bay, P H

    1989-07-01

    This review describes an approach that has been used to assess the skin sensitization risk of new chemicals and product formulations prior to launching the new chemical or product on the market. The risk assessment process utilizes a comparative toxicological approach, in which data on the inherent toxicity of a material, and the exposure to it through manufacturing or consumer use or foreseeable misuse, are integrated and compared with data generated by 'benchmark' materials of similar chemistry or product application, or both. This approach has been valuable in providing an accurate assessment of the skin sensitization potential for a wide range of consumer products and pharmaceuticals, ranging from products with a very transient skin exposure (e.g. some paper products), to cosmetics, to products whose ingredients may be deposited on fabrics and thus result in chronic skin exposure. The risk assessment process described includes both guinea-pig (Buehler) and human skin sensitization test methodologies to evaluate inherent toxicity under relevant epicutaneous exposure conditions. Alternative guinea-pig test methods have been reported to be more sensitive than the Buehler method, particularly those employing intradermal injection of the test material in Freund's complete adjuvant (e.g. maximization test). However, by bypassing the skin barrier at induction, these methods can overstate the sensitization risk of epicutaneous exposure to weak sensitizers (Andersen and Hamann, 1983 and 1984; Matsushita et al., 1975a,b), and can understate the risk to very strong sensitizers possibly through tolerance induction (Buehler, 1985). In addition, materials are tested and classified at concentrations that may not be relevant to anticipated human exposure. The Buehler guinea-pig test data are important in assessing skin sensitization risk in the early phases of product development, where human exposure can be limited, controlled and monitored (e.g. manufacturing employees). The

  2. T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma.

    PubMed

    Moriwaki, Atsushi; Inoue, Hiromasa; Nakano, Takako; Matsunaga, Yuko; Matsuno, Yukiko; Matsumoto, Takafumi; Fukuyama, Satoru; Kan-O, Keiko; Matsumoto, Koichiro; Tsuda-Eguchi, Miyuki; Nagakubo, Daisuke; Yoshie, Osamu; Yoshimura, Akihiko; Kubo, Masato; Nakanishi, Yoichi

    2011-04-01

    CD4(+) T cells, particularly T helper (Th) 2 cells, play a pivotal role in the pathophysiology of allergic asthma. Suppressor of cytokine signaling (SOCS) proteins control the balance of CD4(+) T cell differentiation. Mice that lack SOCS3 in T cells by crossing SOCS3-floxed mice with Lck-Cre-transgenic mice have reduced allergen-induced eosinophilia in the airways. Here, we studied the effects of SOCS3 silencing with small interfering (si) RNA in primary CD4(+) T cells on Th2 cell differentiation and on asthmatic responses in mice. Th2 cells were generated from ovalbumin (OVA)-specific T cell receptor-transgenic mice in vitro and transferred into recipient mice. Transfection of SOCS3-specific siRNA attenuated Th2 response in vitro. Adoptive transfer of SOCS3-siRNA T cells exhibited markedly suppressed airway hyperresponsiveness and eosinophilia after OVA challenge, with a concomitant decrease in OVA-specific CD4(+) T cell accumulation in the airways. To investigate the mechanism of this impaired CD4(+) T cell accumulation, we inactivated SOCS3 of T cells by crossing SOCS3-floxed (SOCS3(flox/flox)) mice with CD4-Cre transgenic mice. CD4-Cre × SOCS3(flox/flox) mice exhibited fewer IL-4-producing cells and more reduced eosinophil infiltration in bronchoalveolar lavage fluids than control mice in a model of OVA-induced asthma. Expression of CCR3 and CCR4 in CD4(+) T cells was decreased in CD4-Cre × SOCS3(flox/flox) mice. CCR4 expression was also decreased in CD4(+) T cells after transfer of SOCS3 siRNA-treated T cells. These findings suggest that the therapeutic modulation of SOCS3 expression in CD4(+) T cells might be effective in preventing the development of allergic asthma.

  3. Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The epithelium lining the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human IgE receptor, CD23 (Fc'RII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monola...

  4. IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice

    PubMed Central

    Jin, Haoli; Oyoshi, Michiko K.; Le, Yi; Bianchi, Teresa; Koduru, Suresh; Mathias, Clinton B.; Kumar, Lalit; Le Bras, Séverine; Young, Deborah; Collins, Mary; Grusby, Michael J.; Wenzel, Joerg; Bieber, Thomas; Boes, Marianne; Silberstein, Leslie E.; Oettgen, Hans C.; Geha, Raif S.

    2008-01-01

    Atopic dermatitis (AD) is a common allergic inflammatory skin disease caused by a combination of intense pruritus, scratching, and epicutaneous (e.c.) sensitization with allergens. To explore the roles of IL-21 and IL-21 receptor (IL-21R) in AD, we examined skin lesions from patients with AD and used a mouse model of allergic skin inflammation. IL-21 and IL-21R expression was upregulated in acute skin lesions of AD patients and in mouse skin subjected to tape stripping, a surrogate for scratching. The importance of this finding was highlighted by the fact that both Il21r–/– mice and WT mice treated with soluble IL-21R–IgG2aFc fusion protein failed to develop skin inflammation after e.c. sensitization of tape-stripped skin. Adoptively transferred OVA-specific WT CD4+ T cells accumulated poorly in draining LNs (DLNs) of e.c. sensitized Il21r–/– mice. This was likely caused by both DC-intrinsic and nonintrinsic effects, because trafficking of skin DCs to DLNs was defective in Il21r–/– mice and, to a lesser extent, in WT mice reconstituted with Il21r–/– BM. More insight into this defect was provided by the observation that skin DCs from tape-stripped WT mice, but not Il21r–/– mice, upregulated CCR7 and migrated toward CCR7 ligands. Treatment of epidermal and dermal cells with IL-21 activated MMP2, which has been implicated in trafficking of skin DCs. These results suggest an important role for IL-21R in the mobilization of skin DCs to DLNs and the subsequent allergic response to e.c. introduced antigen. PMID:19075398

  5. Role of TLR4 in allergic sensitization to food proteins in mice.

    PubMed

    Berin, M C; Zheng, Y; Domaradzki, M; Li, X-M; Sampson, H A

    2006-01-01

    Allergic sensitization to food proteins and other allergens is increasing in prevalence. One hypothesis for this increase is that the decreased rate of infections or exposure to microbial products leaves the immune system susceptible to inappropriate reactivity to innocuous antigens through the lack of development of regulatory cells. We hypothesized that constitutive Toll-like receptor (TLR)4 signaling (presumably via the commensal flora) could inhibit the development of allergic sensitization to food proteins. We tested this hypothesis by sensitizing TLR4+ and TLR4- mice on two genetic backgrounds, C3H and BALB/c, to two common food allergens [beta-lactoglobulin (betaLG) and peanut (PN)]. B-cell responses were not significantly influenced by TLR4 status. T-cell responses were Th2 skewed in TLR4-deficient C3H mice compared with TLR4 sufficient C3H mice, but this pattern of Th2 skewing was not observed in TLR4-deficient mice on a BALB/c background. In anaphylaxis-susceptible C3H mice, TLR4 deficiency was associated with increased severity of anaphylaxis to PN, and decreased severity of anaphylaxis to betaLG. In anaphylaxis-resistant BALB/c mice, TLR4 deficiency was not sufficient to render mice susceptible to PN-induced anaphylaxis. We conclude that although TLR4 status can influence T-cell responses and anaphylaxis severity, the nature of the influence is highly antigen- and strain-dependent.

  6. Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice.

    PubMed

    Miyamoto, Shintaro; Hattori, Noboru; Senoo, Tadashi; Onari, Yojiro; Iwamoto, Hiroshi; Kanehara, Masashi; Ishikawa, Nobuhisa; Fujitaka, Kazunori; Haruta, Yoshinori; Murai, Hiroshi; Yokoyama, Akihito; Kohno, Nobuoki

    2011-12-01

    Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-β levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.

  7. Active sensitization and occupational allergic contact dermatitis caused by para-tertiary-butylcatechol.

    PubMed

    Estlander, T; Kostiainen, M; Jolanki, R; Kanerva, L

    1998-02-01

    Para-tertiary-butylcatechol (PTBC) is a rare allergen which is used in the rubber, paint and petroleum industries. We present 9 patients who were sensitized to PTBC and examined at the Finnish Institute of Occupational Health (FIOH) between 1974 and 1995. 3 of the patients had been exposed to PTBC in their work. 2 of them also had allergic reactions to para-tertiary-butylphenol (PTBP)-formaldehyde resin and to PTBP. 5 of the patients became sensitized to PTBC from patch testing. PTBC was found to be one of the most common causes of active sensitization in our clinic. Accordingly, at the FIOH, the patch test concentration of PTBC was lowered to 0.25% and this lower concentration is recommended for general use.

  8. Pulmonary dendritic cell distribution and prevalence in guinea pig airways: effect of ovalbumin sensitization and challenge.

    PubMed

    Lawrence, T E; Millecchia, L L; Frazer, D G; Fedan, J S

    1997-08-01

    We characterized the localization and prevalence of dendritic cells (DC) in guinea pig airways before and after s.c. sensitization and aerosol challenge with ovalbumin (OVA). DC, eosinophils, macrophages, T cells and B cells in lung and trachea were identified and quantified in frozen sections using monoclonal antibodies and computer-assisted image analysis. Airway reactivity of conscious animals to inhaled methacholine was examined. In unsensitized animals, DC were localized primarily within the lamina propria of the trachea and bronchi, in the submucosa of the trachea and in the adventitia of the bronchi. In contrast to reported studies on rats, few DC were noted in the epithelium. After OVA challenge, sensitized animals demonstrated an early obstructive response and a late-phase response that was well developed by 18 hr. Challenge with OVA increased DC prevalence in the lamina propria and submucosa of the trachea and in the lamina propria and adventitia of the bronchi. There was widespread eosinophilia throughout the airways, but no changes in B cells or T cells were evident. Macrophages were increased in the epithelium of both OVA-treated and saline-treated animals. At 18 hr after challenge, sensitized guinea pigs but not saline-treated controls were hyperreactive to inhaled methacholine. Except for macrophages, none of these effects were observed after saline treatment. Our findings indicate that inflammation in the airways of OVA-sensitized guinea pigs involves infiltration of DC, which is seen at the time animals are hyperreactive to inhaled methacholine. PMID:9262368

  9. The Impact of Aspergillus fumigatus Viability and Sensitization to Its Allergens on the Murine Allergic Asthma Phenotype

    PubMed Central

    Pandey, Sumali; Hoselton, Scott A.; Schuh, Jane M.

    2013-01-01

    Aspergillus fumigatus is a ubiquitously present respiratory pathogen. The outcome of a pulmonary disease may vary significantly with fungal viability and host immune status. Our objective in this study was (1) to assess the ability of inhaled irradiation-killed or live A. fumigatus spores to induce allergic pulmonary disease and (2) to assess the extent to which inhaled dead or live A. fumigatus spores influence pulmonary symptoms in a previously established allergic state. Our newly developed fungal delivery apparatus allowed us to recapitulate human exposure through repeated inhalation of dry fungal spores in an animal model. We found that live A. fumigatus spore inhalation led to a significantly increased humoral response, pulmonary inflammation, and airway remodeling in naïve mice and is more likely to induce allergic asthma symptoms than the dead spores. In contrast, in allergic mice, inhalation of dead and live conidia recruited neutrophils and induced goblet cell metaplasia. This data suggests that asthma symptoms might be exacerbated by the inhalation of live or dead spores in individuals with established allergy to fungal antigens, although the extent of symptoms was less with dead spores. These results are likely to be important while considering fungal exposure assessment methods and for making informed therapeutic decisions for mold-associated diseases. PMID:24063011

  10. Two cases of cross-sensitivity in subjects allergic to paraphenylenediamine following ingestion of Polaronil.

    PubMed

    Sornin de Leysat, C; Boone, M; Blondeel, A; Song, M

    2003-01-01

    We report the cases of 2 women presenting allergy to paraphenylenediamine (PPD). Both patients had a history of eczema that worsened following the ingestion of the antihistamine Polaronil (dexamethasone/dexchlorpheniramine). This clinical presentation could be explained by cross-sensitivity to sulfanilic acid (4-aminobenzene sulfonic acid), a metabolite of sunset yellow (FD&C No. 6). Sunset yellow is an azo dye present in this tablet. Indeed, PPD-allergic subjects may suffer from cross-sensitivity to related compounds, especially to those that can be ingested such as azo dyes. Such compounds are used in some instances by the food and pharmaceutical industries, but their presence is often undisclosed. PMID:12771491

  11. Prenatal allergic sensitization to helminth antigens in offspring of parasite-infected mothers.

    PubMed Central

    Weil, G J; Hussain, R; Kumaraswami, V; Tripathy, S P; Phillips, K S; Ottesen, E A

    1983-01-01

    Total and filaria-specific immunoglobulin E (IgE) levels were studied in cord blood from infants born in Madras, India, where filariasis and intestinal helminth infections are highly endemic. Increased total IgE levels were observed in 82% of 57 cord sera tested (geometric mean 12.6 ng/ml; range 1-1,900 ng/ml). 33 of these sera also contained IgE antibodies specific for filarial antigens as determined by solid-phase radioimmunoassay. Comparison of ratios of filaria-specific IgE to total IgE in paired maternal and cord sera suggested that cord blood IgE was derived from the fetus in most cases and not from transplacental antibody transfer. Our results suggest that prenatal allergic sensitization to helminth parasites occurs in the tropics. Such sensitization may contribute to the heterogeneity in host immune response and disease expression noted in filariasis and other helminth infections. PMID:6343433

  12. PKU-related dysgammaglobulinaemia: the effect of diet therapy on IgE and allergic sensitization.

    PubMed

    Riva, E; Fiocchi, A; Agostoni, C; Biasucci, G; Sala, M; Banderali, G; Luotti, D; Giovannini, M

    1994-01-01

    The effect of diet on the development of immunoallergic signs and symptoms in children with phenylketonuria (PKU) was evaluated. Immunological indices of 58 children with PKU treated with diets were compared to the immunological indices of 58 healthy (non-PKU) children. In the PKU group, 39 children had been placed on diet therapy within the first month of life; 19 children had been placed on diet therapy after 6 months of age. Total circulating lymphocytes; CD3+, CD4+, CD8+ circulating lymphocytes; and serum IgA, IgM, IgG and total IgE levels were measured for each child. Skin prick tests were performed for common inhalant and food allergens. Every 3 months over the 2-year period of this study, the signs and symptoms of eczema, allergic rhinitis and asthma were recorded. The PKU group had lower IgG levels (p = 0.004) and higher total IgE levels (p = 0.0001) than the control group. Significantly lower IgE levels were found in children started on diet therapy within the first month of life compared with those started on diet therapy after 6 months of age (p = 0.0001). Allergic sensitization was significantly more frequent in the PKU group (24/58 vs 13/58, z = 2.00, p < 0.05), but no significant difference in the incidence of eczema and allergic rhinitis was found. Asthma was less frequent in the PKU group than in the control group (5/58 vs 14/58, z = 2.09, p < 0.05). Thus, diet appeared to prevent the development of immunoallergic signs and symptoms.

  13. Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma.

    PubMed

    Xu, Wanting; Chen, Ling; Guo, Sheng; Wu, Liangxia; Zhang, Jianhua

    2016-01-01

    Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation.

  14. Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma.

    PubMed

    Xu, Wanting; Chen, Ling; Guo, Sheng; Wu, Liangxia; Zhang, Jianhua

    2016-01-01

    Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation. PMID:26974537

  15. Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis.

    PubMed

    Sharma, Nripen S; Jindal, Rohit; Mitra, Bhaskar; Lee, Serom; Li, Lulu; Maguire, Tim J; Schloss, Rene; Yarmush, Martin L

    2012-03-01

    Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development of in vitro methods to assess chemical sensitivity. In this paper, we examine existing approaches including in silico models, cell and tissue based assays for distinguishing between sensitizers and irritants. The in silico approaches that have been discussed include Quantitative Structure Activity Relationships (QSAR) and QSAR based expert models that correlate chemical molecular structure with biological activity and mechanism based read-across models that incorporate compound electrophilicity. The cell and tissue based assays rely on an assortment of mono and co-culture cell systems in conjunction with 3D skin models. Given the complexity of allergen induced immune responses, and the limited ability of existing systems to capture the entire gamut of cellular and molecular events associated with these responses, we also introduce a microfabricated platform that can capture all the key steps involved in allergic contact sensitivity. Finally, we describe the development of an integrated testing strategy comprised of two or three tier systems for evaluating sensitization potential of chemicals.

  16. Sensitization Rates for Various Allergens in Children with Allergic Rhinitis in Qingdao, China

    PubMed Central

    Lin, Hang; Lin, Rongjun; Li, Na

    2015-01-01

    The aim of this study was to determine the prevalence of sensitization to common allergens in children with allergic rhinitis (AR) living in Qingdao, China. We conducted a retrospective analysis for AR cases, who underwent skin prick tests (SPT) in Qingdao. A total of 2841 children with AR qualified for the inclusion criteria (Age 3–5 years: 1500 children; Age 6–12 years: 1341 children). The most common inhaled allergens to which the AR children were sensitive were Dermatophagoides pteronyssinus (69.3%), Dermatophagoides farinae (66.2%) and mould 1 (Penicillium notatum 38.9%); while the corresponding ingested allergens were mussel (39.2%), shrimp (36.3%) and carp (36.5%). The prevalence of sensitization to inhaled allergens and food allergens was higher in children >6 years of age as compared to that in children 3–5 years of age (all p < 0.05). Children >6 years old were more sensitive to dust mite as compared to children 3–5 years old (p < 0.05). Sensitization to dust mite was more common in males than in females (p = 0.05). In this study, Dermatophagoides pteronyssinus and Dermatophagoides farinae were the most common allergens causing AR in children in Qingdao, China. Older children with AR, particularly males, were found to be more sensitive to dust mite. PMID:26371014

  17. [Changes in food allergen sensitization rates of Japanese allergic children during the last 15 years].

    PubMed

    Kusunoki, Takashi; Miyanomae, Takeshi; Inoue, Yasuhiro; Itoh, Masatoshi; Yoshioka, Takakazu; Okafuji, Ikuo; Nishikomori, Ryuta; Heike, Toshio; Nakahata, Tatsutoshi

    2004-07-01

    In order to evaluate the changes in food allergen sensitization rates of allergic children, serum samples from 85 patients about 15 years ago (past group) and those from 90 current patients (present group) were randomly selected, and the specific IgE for six food allergens (wheat, peanuts, sesame, mackerel, ovomucoid, and kiwi) were measured with the CAP-RAST system. Sensitivity rates (class 2 or higher) for wheat and peanuts were significantly higher in the present than in the past group. Although there was no statistical difference in sensitivity rates (class 2 or higher) for kiwi between the groups, sensitivity rates (class 1 or higher) of the present group were significantly higher than those of the past group, indicating that the number of cases mildly sensitized to kiwi has been increasing. This trend was especially marked among children aged 6 or younger, and there was no statistical difference in sensitivity rates among those aged 7 or older. For the management of food allergy, special attention should therefore be paid not only to an increase in the number of patients, but also to changes in the kinds of causative foods.

  18. Sensitization Rates for Various Allergens in Children with Allergic Rhinitis in Qingdao, China.

    PubMed

    Lin, Hang; Lin, Rongjun; Li, Na

    2015-09-07

    The aim of this study was to determine the prevalence of sensitization to common allergens in children with allergic rhinitis (AR) living in Qingdao, China. We conducted a retrospective analysis for AR cases, who underwent skin prick tests (SPT) in Qingdao. A total of 2841 children with AR qualified for the inclusion criteria (Age 3-5 years: 1500 children; Age 6-12 years: 1341 children). The most common inhaled allergens to which the AR children were sensitive were Dermatophagoides pteronyssinus (69.3%), Dermatophagoides farinae (66.2%) and mould 1 (Penicillium notatum 38.9%); while the corresponding ingested allergens were mussel (39.2%), shrimp (36.3%) and carp (36.5%). The prevalence of sensitization to inhaled allergens and food allergens was higher in children >6 years of age as compared to that in children 3-5 years of age (all p < 0.05). Children >6 years old were more sensitive to dust mite as compared to children 3-5 years old (p < 0.05). Sensitization to dust mite was more common in males than in females (p = 0.05). In this study, Dermatophagoides pteronyssinus and Dermatophagoides farinae were the most common allergens causing AR in children in Qingdao, China. Older children with AR, particularly males, were found to be more sensitive to dust mite.

  19. Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection.

    PubMed

    Gazzinelli-Guimarães, Pedro H; Bonne-Année, Sandra; Fujiwara, Ricardo T; Santiago, Helton C; Nutman, Thomas B

    2016-10-01

    Among the various hypotheses put forward to explain the modulatory influence of helminth infection on allergic effector responses in humans, the IL-10-induced suppression of Th2-associated responses has been the leading candidate. To explore this helminth/allergy interaction more fully, parasite- and allergen-specific CD4(+) T cell responses in 12 subjects with filarial infections, and coincident allergic sensitization (filarial [Fil](+)allergy [A](+)) were compared with the responses to three appropriate control groups (Fil(-)A(-) [n = 13], Fil(-)A(+) [n = 12], Fil(+)A(-) [n = 11]). The most important findings revealed that Fil(+)A(+) had marked (p < 0.0001 for all cytokines) increases in parasite Ag-driven Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), and the regulatory (IL-10) cytokines when compared with Fil(+)A(-) Moreover, using multiparameter flow cytometry, filarial parasite Ag induced a marked increase in not only the frequency of CD4(+) T cells producing IL-4, IL-5, IL-2, and TNF-α in Fil(+)A(+) when compared with Fil(+)A(-) patients, but also in the frequencies of polyfunctional Th2-like (CD4(+)IL-4(+)IL-5(+) and CD4(+)IL-2(+)IL-4(+)IL-5(+)TNF-α(+)) cells. The Th2-associated responses seen in the Fil(+)A(+) group were correlated with serum IgE levels (p < 0.01, r = 0.5165 for IL-4; p < 0.001, r = 0.5544 for IL-5; and p < 0.001, r = 0.4901 for IL-13) and levels of circulating eosinophils (p < 0.0116, r = 0.5656) and their degranulation/activation products (major basic protein [p < 0.001, r = 0.7353] and eosinophil-derived neurotoxin [p < 0.01, r = 0.7059]). CD4(+) responses to allergen were not different (to a large extent) among the groups. Taken together, our data suggest that allergic sensitization coincident with filarial infection drives parasite Ag-specific T cell hyperresponsiveness, which is characterized largely by an augmented Th2-dominated immune response. PMID:27566825

  20. Vascular endothelial growth factor as a key inducer of angiogenesis in the asthmatic airways.

    PubMed

    Meyer, Norbert; Akdis, Cezmi A

    2013-02-01

    Asthma is a chronic inflammatory disease of the airways characterized by structural airway changes, which are known as airway remodeling, including smooth muscle hypertrophy, goblet cell hyperplasia, subepithelial fibrosis, and angiogenesis. Vascular remodeling in asthmatic lungs results from increased angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF). VEGF is a key regulator of blood vessel growth in the airways of asthma patients by promoting proliferation and differentiation of endothelial cells and inducing vascular leakage and permeability. In addition, VEGF induces allergic inflammation, enhances allergic sensitization, and has a role in Th2 type inflammatory responses. Specific inhibitors of VEGF and blockers of its receptors might be useful to control chronic airway inflammation and vascular remodeling, and might be a new therapeutic approach for chronic inflammatory airway disease like asthma.

  1. Urban Tree Canopy and Asthma, Wheeze, Rhinitis, and Allergic Sensitization to Tree Pollen in a New York City Birth Cohort

    PubMed Central

    Lovasi, Gina S.; O’Neil-Dunne, Jarlath P.M.; Lu, Jacqueline W.T.; Sheehan, Daniel; Perzanowski, Matthew S.; MacFaden, Sean W.; King, Kristen L.; Matte, Thomas; Miller, Rachel L.; Hoepner, Lori A.; Perera, Frederica P.

    2013-01-01

    Background: Urban landscape elements, particularly trees, have the potential to affect airflow, air quality, and production of aeroallergens. Several large-scale urban tree planting projects have sought to promote respiratory health, yet evidence linking tree cover to human health is limited. Objectives: We sought to investigate the association of tree canopy cover with subsequent development of childhood asthma, wheeze, rhinitis, and allergic sensitization. Methods: Birth cohort study data were linked to detailed geographic information systems data characterizing 2001 tree canopy coverage based on LiDAR (light detection and ranging) and multispectral imagery within 0.25 km of the prenatal address. A total of 549 Dominican or African-American children born in 1998–2006 had outcome data assessed by validated questionnaire or based on IgE antibody response to specific allergens, including a tree pollen mix. Results: Tree canopy coverage did not significantly predict outcomes at 5 years of age, but was positively associated with asthma and allergic sensitization at 7 years. Adjusted risk ratios (RRs) per standard deviation of tree canopy coverage were 1.17 for asthma (95% CI: 1.02, 1.33), 1.20 for any specific allergic sensitization (95% CI: 1.05, 1.37), and 1.43 for tree pollen allergic sensitization (95% CI: 1.19, 1.72). Conclusions: Results did not support the hypothesized protective association of urban tree canopy coverage with asthma or allergy-related outcomes. Tree canopy cover near the prenatal address was associated with higher prevalence of allergic sensitization to tree pollen. Information was not available on sensitization to specific tree species or individual pollen exposures, and results may not be generalizable to other populations or geographic areas. PMID:23322788

  2. EFFECTS OF DIESEL EXHAUST ON PULMONARY RESPONSES DURING ALLERGIC SENSITIZATION TO AEROSOLIZED OVALBUMIN IN BALB/C MICE

    EPA Science Inventory

    Effects of Diesel Exhaust on Pulmonary Responses During Allergic Sensitization to Aerosolized Ovalbumin in BALB/c Mice. P. Singh1, M.J. Daniels1, D. Andrews1, E. Boykin1, W. P. Linak2 and M.I. Gilmour1. 1USEPA, ORD, NHEERL, RTP, NC. 2 USEPA, ORD, NRMRL, RTP, NC.

    Inhala...

  3. Airway surface liquid volume expansion induces rapid changes in amiloride-sensitive Na+ transport across upper airway epithelium-Implications concerning the resolution of pulmonary edema.

    PubMed

    Azizi, Fouad; Arredouani, Abdelilah; Mohammad, Ramzi M

    2015-09-01

    During airway inflammation, airway surface liquid volume (ASLV) expansion may result from the movement of plasma proteins and excess liquid into the airway lumen due to extravasation and elevation of subepithelial hydrostatic pressure. We previously demonstrated that elevation of submucosal hydrostatic pressure increases airway epithelium permeability resulting in ASLV expansion by 500 μL cm(-2) h(-1). Liquid reabsorption by healthy airway epithelium is regulated by active Na(+) transport at a rate of 5 μL cm(-2) h(-1). Thus, during inflammation the airway epithelium may be submerged by a large volume of luminal liquid. Here, we have investigated the mechanism by which ASLV expansion alters active epithelial Na(+) transport, and we have characterized the time course of the change. We used primary cultures of tracheal airway epithelium maintained under air interface (basal ASLV, depth is 7 ± 0.5 μm). To mimic airway flooding, ASLV was expanded to a depth of 5 mm. On switching from basal to expanded ASLV conditions, short-circuit current (Isc, a measure of total transepithelial active ion transport) declined by 90% with a half-time (t1/2) of 1 h. 24 h after the switch, there was no significant change in ATP concentration nor in the number of functional sodium pumps as revealed by [(3)H]-ouabain binding. However, amiloride-sensitive uptake of (22)Na(+) was reduced by 70% upon ASLV expansion. This process is reversible since after returning cells back to air interface, Isc recovered with a t1/2 of 5-10 h. These results may have important clinical implications concerning the development of Na(+) channels activators and resolution of pulmonary edema.

  4. Airway oxidative stress causes vascular and hepatic inflammation via upregulation of IL-17A in a murine model of allergic asthma.

    PubMed

    Al-Harbi, Naif O; Nadeem, Ahmed; Al-Harbi, Mohammed M; Ansari, Mushtaq A; AlSharari, Shakir D; Bahashwan, Saleh A; Attia, Sabry M; Al-Hosaini, Khaled A; Al Hoshani, Ali R; Ahmad, Sheikh F

    2016-05-01

    Oxidants are generated in asthmatic airways due to infiltration of inflammatory leukocytes and resident cells in the lung. Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide radical may leak into systemic circulation when generated in uncontrolled manner and may impact vasculature. Our previous studies have shown an association between airway inflammation and systemic inflammation; however so far none has investigated the impact of airway oxidative inflammation on hepatic oxidative stress and Th1/Th2/Th17 cytokine markers in liver/vasculature in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of systemic/hepatic Th1/Th2/Th17 cytokines balance and hepatic oxidative stress. Mice were sensitized intraperitoneally with cockroach extract (CE) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with CE. Mice were then assessed for systemic/hepatic inflammation through assessment of Th1/Th2/Th17 cytokines and oxidative stress (iNOS, protein nitrotyrosine, lipid peroxides and myeloperoxidase activity). Challenge with CE led to increased Th2/Th17 cytokines in blood/liver and hepatic oxidative stress. However, only Th17 related pro-inflammatory markers were upregulated by hydrogen peroxide (H2O2) inhalation in vasculature and liver, whereas antioxidant treatment, N-acetyl cysteine (NAC) downregulated them. Hepatic oxidative stress was also upregulated by H2O2 inhalation, whereas NAC attenuated it. Therefore, our study shows that airway oxidative inflammation may contribute to systemic inflammation through upregulation of Th17 immune responses in blood/liver and hepatic oxidative stress. This might predispose these patients to increased risk for the development of cardiovascular disorders.

  5. Lymphocyte Gene Expression Characteristic of Immediate Airway Responses (IAR) and Methacholine (MCH) Hyperresponsiveness in Mice Sensitized and Challenged with Isocyanates

    EPA Science Inventory

    Exposure to isocyanates has been associated with occupational airway diseases, including asthma. Previously we reported on respiratory and immune responses following dermal sensitization and intranasal challenge of BALB/c mice with 6 different isocyanates. The purpose of this st...

  6. Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity

    PubMed Central

    Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus; Claeson, Anna-Sara; Lind, Nina; Nordin, Steven; Brix, Susanne

    2015-01-01

    Background Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. Objectives The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. Method Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. Results The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. Conclusion We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes. PMID:26599866

  7. Lower Prevalence of Atopic Dermatitis and Allergic Sensitization among Children and Adolescents with a Two-Sided Migrant Background

    PubMed Central

    Ernst, Sinja Alexandra; Schmitz, Roma; Thamm, Michael; Ellert, Ute

    2016-01-01

    In industrialized countries atopic diseases have been reported to be less likely in children and adolescents with a migrant background compared to non-migrants. This paper aimed at both examining and comparing prevalence of asthma, allergic rhinoconjunctivitis and atopic dermatitis and allergic sensitization to specific IgE antibodies in children and adolescents with and without a migrant background. Using data of the population-based German Health Interview and Examination Survey for children and adolescents (KiGGS; n = 17,450; 0–17 years), lifetime and 12-month prevalence of atopic diseases and point prevalence of 20 common allergic sensitizations were investigated among migrants compared to non-migrants. Multiple regression models were used to estimate the association of atopic disease and allergic sensitization with migrant background. In multivariate analyses with substantial adjustment we found atopic dermatitis about one-third less often (OR 0.73, 0.57–0.93) in participants with a two-sided migrant background. Statistically significant associations between allergic sensitizations and a two-sided migrant background remained for birch (OR 0.73, 0.58–0.90), soybean (OR 0.72, 0.54–0.96), peanut (OR 0.69, 0.53–0.90), rice (OR 0.64, 0.48–0.87), potato (OR 0.64, 0.48–0.85), and horse dander (OR 0.58, 0.40–0.85). Environmental factors and living conditions might be responsible for the observed differences. PMID:26927147

  8. Preparation of a Paeonol-Containing Temperature-Sensitive In Situ Gel and Its Preliminary Efficacy on Allergic Rhinitis

    PubMed Central

    Chu, Kedan; Chen, Lidian; Xu, Wei; Li, Huang; Zhang, Yuqin; Xie, Weirong; Zheng, Jian

    2013-01-01

    In this paper, the optimal composition of a paeonol temperature-sensitive in situ gel composed of poloxamer 407 (P407) was determined, and a preliminary study of its effect on allergic rhinitis was performed. The optimal composition of the paeonol temperature-sensitive in situ gel included 2% paeonol inclusion, 22% P407, 2% poloxamer 188 (P188) and 2% PEG6000, as assessed by thermodynamic and rheological studies. The toad palate model was employed to study the toxicity of the paeonol temperature-sensitive in situ gel on the nasal mucosa. The result of this experiment showed low toxicity to cilia, which allows the gel to be used for nasal administration. The Franz diffusion cell method was used to study the in vitro release of paeonol and suggested that the in vitro release was in line with the Higuchi equation. This result suggests that the paeonol could be absorbed into the body through mucous membranes and had some characteristics of a sustained effect. Finally, the guinea pig model of ovalbumin sensitized allergic rhinitis was used to evaluate the preliminary efficacy of the gel, with the paeonol temperature-sensitive in situ gel showing a significant effect on the guinea pig model of sensitized allergic rhinitis (AR). PMID:23525047

  9. TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD

    PubMed Central

    Thorburn, Alison N.; Tseng, Hsin-Yi; Donovan, Chantal; Hansbro, Nicole G.; Jarnicki, Andrew G.; Foster, Paul S.; Gibson, Peter G.; Hansbro, Philip M.

    2016-01-01

    Background Exposure to non-pathogenic Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88). The involvement of TLR2, TLR4 and MyD88 in the pathogenesis of AAD and asthma is incompletely understood, and has not been studied in S. pneumoniae-mediated suppression of AAD. We investigated the role of TLR2, TLR4 and MyD88 in the development of AAD and S. pneumoniae-mediated suppression of AAD. Methods and Findings OVA-induced AAD and killed S. pneumoniae-mediated suppression of AAD were assessed in wild-type, TLR2-/-, TLR4-/-, TLR2/4-/- and MyD88-/- BALB/c mice. During OVA-induced AAD, TLR2, TLR4 and MyD88 were variously involved in promoting eosinophil accumulation in bronchoalveolar lavage fluid and blood, and T-helper type (Th)2 cytokine release from mediastinal lymph node T cells and splenocytes. However, all were required for the induction of airways hyperresponsiveness (AHR). In S. pneumoniae-mediated suppression of AAD, TLR2, TLR4 and MyD88 were variously involved in the suppression of eosinophilic and splenocyte Th2 responses but all were required for the reduction in AHR. Conclusions These results highlight important but complex roles for TLR2, TLR4 and MyD88 in promoting the development of OVA-induced AAD, but conversely in the S. pneumoniae-mediated suppression of AAD, with consistent and major contributions in both the induction and suppression of AHR. Thus, TLR signaling is likely required for both the development of asthma and the

  10. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

    PubMed Central

    Lee, Chen-Chen; Wang, Ching-Chiung; Huang, Huei-Mei; Lin, Chu-Lun; Leu, Sy-Jye; Lee, Yueh-Lun

    2015-01-01

    This study investigated the immunomodulatory effects of ferulic acid (FA) on antigen-presenting dendritic cells (DCs) in vitro and its antiallergic effects against ovalbumin- (OVA-) induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation induced a high level of interleukin- (IL-) 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF-) α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4), MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE) and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13), and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN-) γ production in bronchoalveolar lavage fluid (BALF) and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model. PMID:26495021

  11. Sensitization pattern of crustacean-allergic individuals can indicate allergy to molluscs.

    PubMed

    Vidal, C; Bartolomé, B; Rodríguez, V; Armisén, M; Linneberg, A; González-Quintela, A

    2015-11-01

    This study investigated the sensitization pattern of crustacean-allergic patients according to tolerance to molluscs. Thirty-one patients with anaphylaxis to crustaceans (14 with mollusc allergy and 17 with mollusc tolerance) were studied using skin prick tests (SPTs), specific IgEs (sIgEs) and SDS-PAGE immunoblotting. IgE-reactive shrimp proteins were identified by proteomic analyses. Patients with mollusc allergy presented more frequently SPTs positive to molluscs and higher sIgE titres in response to both molluscs and crustaceans. Shrimp-sIgE and rPen a1-sIgE values of 1.57 kUA /l and 4.38 kUA /l, respectively, showed positive likelihood ratios of 4.3 and 10.9 for the identification of mollusc allergy. Patients with mollusc allergy reacted more frequently to tropomyosin in immunoblots than did patients without it (93% vs 35%, respectively, P = 0.004). Reactivity to proteins other than tropomyosin (n = 14) was not different between the two groups. Among patients with crustacean anaphylaxis, patients with mollusc allergy and mollusc tolerance show a different pattern of sensitization, something that may help identify them.

  12. Allergic sensitization frequency and wheezing differences in early life between black and white children.

    PubMed

    Wegienka, Ganesa; Havstad, Suzanne; Joseph, Christine L M; Zoratti, Edward; Ownby, Dennis; Johnson, Christine Cole

    2012-01-01

    Asthma is more common in black children than in white children. Allergic sensitization has been shown to be associated with increased likelihood of asthma. This study was designed to determine whether there are racial differences in the allergens to which children are sensitized in the Detroit metropolitan area and determine whether sensitization was associated with wheeze outcomes. Pregnant women were recruited for the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study birth cohort to follow the health of their children in the Detroit metropolitan area. Specific IgE (sIgE) was measured for Alternaria, cat, cockroach, dog, Dermatophagoides farinae, short ragweed, timothy grass, egg, milk, and peanut in blood samples from the children at age 2 years. A positive allergen sIgE was defined as ≥0.35 IU/mL. Mothers reported their child's race and completed interviews at age 2 years about characteristics of wheezing episodes in their child (frequency, medication, acute care, or emergency department visit). Black children (n = 384) were more likely than white children (n = 180) to have been positive for each of the allergens tested and also tended to have positive responses to a greater number of allergens (four or more allergens: 9.2% versus 3.5%). Children who had two or more positive sIgEs (adjusted odds ratio [aOR] = 2.68; 95% 95% confidence interval [CI], 1.33, 5.46) or three or more positive sIgEs (aOR = 2.67, 95% CI, 1.19, 6.01) were more likely to have wheezed four or more times in the last 12 months. Racial differences in sensitization at this young age may contribute to the racial difference in asthma prevalence at later ages.

  13. Allergic sensitization frequency and wheezing differences in early life between black and white children.

    PubMed

    Wegienka, Ganesa; Havstad, Suzanne; Joseph, Christine L M; Zoratti, Edward; Ownby, Dennis; Johnson, Christine Cole

    2012-01-01

    Asthma is more common in black children than in white children. Allergic sensitization has been shown to be associated with increased likelihood of asthma. This study was designed to determine whether there are racial differences in the allergens to which children are sensitized in the Detroit metropolitan area and determine whether sensitization was associated with wheeze outcomes. Pregnant women were recruited for the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study birth cohort to follow the health of their children in the Detroit metropolitan area. Specific IgE (sIgE) was measured for Alternaria, cat, cockroach, dog, Dermatophagoides farinae, short ragweed, timothy grass, egg, milk, and peanut in blood samples from the children at age 2 years. A positive allergen sIgE was defined as ≥0.35 IU/mL. Mothers reported their child's race and completed interviews at age 2 years about characteristics of wheezing episodes in their child (frequency, medication, acute care, or emergency department visit). Black children (n = 384) were more likely than white children (n = 180) to have been positive for each of the allergens tested and also tended to have positive responses to a greater number of allergens (four or more allergens: 9.2% versus 3.5%). Children who had two or more positive sIgEs (adjusted odds ratio [aOR] = 2.68; 95% 95% confidence interval [CI], 1.33, 5.46) or three or more positive sIgEs (aOR = 2.67, 95% CI, 1.19, 6.01) were more likely to have wheezed four or more times in the last 12 months. Racial differences in sensitization at this young age may contribute to the racial difference in asthma prevalence at later ages. PMID:23394507

  14. Anti-allergic activity of R-phycocyanin from Porphyra haitanensis in antigen-sensitized mice and mast cells.

    PubMed

    Liu, Qingmei; Wang, Youzhao; Cao, Minjie; Pan, Tzuming; Yang, Yang; Mao, Haiyan; Sun, Lechang; Liu, Guangming

    2015-04-01

    The prevalence of food allergy has increased in Asian countries. Marine algae have been proposed as the potential resource for anti-allergic therapeutics. The present study was aimed at isolating R-phycocyanin (RPC) from Porphyra haitanensis and determining the anti-allergy potential of RPC in antigen-sensitized mice and mast cells. In animal experiments, RPC could effectively reduce tropomyosin (TM)-specific immunoglobulin E (IgE) and histamine levels, alleviate allergy symptoms and jejunum tissue inflammation in mice, and inhibit the expression and release of cytokines (interleukin-4 (IL-4) and IL-13) in peritoneal lavage fluid. In spleen lymphocyte experiments, high purity of RPC skewed the immunological function of CD4(+) T cells towards Th1 activity. A higher expression of interferon (IFN)-γ was induced by a synergistic effect of TM and RPC. Through the Jun N-terminal kinase and Janus kinase 2 signaling pathways, IFN-γ synthesis was induced by RPC in combination with TM. Anti-allergic effect of RPC was evaluated in IgE-mediated rat mast RBL-2H3 cells. The results demonstrated that RPC inhibited allergy markers, including the release of β-hexosaminidase, histamine and ROS in antigen-sensitized RBL-2H3 cells. RPC also suppressed the production of pro-inflammatory factors (IL-4 and tumor necrosis factor-α). In conclusion, RPC decreased allergic sensitization against TM by blocking Th2 cell polarization as well as suppressed the release of allergic-mediators in antigen-stimulated mast cells. It may be used as a functional food component or active pharmaceutical ingredient for allergic patients.

  15. Anti-allergic activity of R-phycocyanin from Porphyra haitanensis in antigen-sensitized mice and mast cells.

    PubMed

    Liu, Qingmei; Wang, Youzhao; Cao, Minjie; Pan, Tzuming; Yang, Yang; Mao, Haiyan; Sun, Lechang; Liu, Guangming

    2015-04-01

    The prevalence of food allergy has increased in Asian countries. Marine algae have been proposed as the potential resource for anti-allergic therapeutics. The present study was aimed at isolating R-phycocyanin (RPC) from Porphyra haitanensis and determining the anti-allergy potential of RPC in antigen-sensitized mice and mast cells. In animal experiments, RPC could effectively reduce tropomyosin (TM)-specific immunoglobulin E (IgE) and histamine levels, alleviate allergy symptoms and jejunum tissue inflammation in mice, and inhibit the expression and release of cytokines (interleukin-4 (IL-4) and IL-13) in peritoneal lavage fluid. In spleen lymphocyte experiments, high purity of RPC skewed the immunological function of CD4(+) T cells towards Th1 activity. A higher expression of interferon (IFN)-γ was induced by a synergistic effect of TM and RPC. Through the Jun N-terminal kinase and Janus kinase 2 signaling pathways, IFN-γ synthesis was induced by RPC in combination with TM. Anti-allergic effect of RPC was evaluated in IgE-mediated rat mast RBL-2H3 cells. The results demonstrated that RPC inhibited allergy markers, including the release of β-hexosaminidase, histamine and ROS in antigen-sensitized RBL-2H3 cells. RPC also suppressed the production of pro-inflammatory factors (IL-4 and tumor necrosis factor-α). In conclusion, RPC decreased allergic sensitization against TM by blocking Th2 cell polarization as well as suppressed the release of allergic-mediators in antigen-stimulated mast cells. It may be used as a functional food component or active pharmaceutical ingredient for allergic patients. PMID:25746371

  16. [Non-allergic gluten sensitivity. A controversial disease - or not yet sufficiently explored?].

    PubMed

    Raithel, Martin; Kluger, Anna Katharina; Dietz, Birgit; Hetterich, Urban

    2016-07-01

    The avoidance of wheat, gluten and other cereal products is a growing phenomenon in industrialized countries. The diagnostic criteria of celiac disease and of food allergy to wheat flour and/or other cereals are clearly defined. Only about 0.5-25 % of the population are affected from both of these immunological diseases.Nevertheless, there exists a significantly greater proportion of people reporting at least subjectively significant complaints and quality of life improvements after switching to a wheat- or gluten-free diet. Celiac disease or wheat allergy cannot be detected in these individuals on the basis of established criteria. The absence of clear diagnostic autoimmune or allergic criteria in these wheat sensitive patients has resulted in the description of non-celiac gluten sensitivity.It is clinically detectable in only very few individuals and may manifest with either intestinal, extra-intestinal or neurovegetative and psychosomatic symptoms, respectively. However, non-celiac disease gluten sensitivity has to be differentiated critically from irritable bowel syndrome, carbohydrate malassimilation, postinfectious conditions and psychosomatic diseases.Pathophysiologically, non-celiac disease gluten sensitivity is still poorly characterized; several non-immunological mechanisms are discussed to contribute to non-celiac gluten sensitivity. These include the effects of fructo- and galacto-oligosaccharides, of trypsin inhibitors of amylase, and wheat lectin agglutinins, which may influence or modulate intestinal permeability and/or a non-specific immune or effector cell degranulation within the gastrointestinal tract. In addition, further metabolic effects with direct or indirect influence on the intestinal flora are currently discussed.In addition to subjectively reported changes in symptoms that may affect variably intestinal, as well as extra-intestinal and/or neuropsychiatric symptoms, some studies suggest that there is little reproducibility of

  17. [Non-allergic gluten sensitivity. A controversial disease - or not yet sufficiently explored?].

    PubMed

    Raithel, Martin; Kluger, Anna Katharina; Dietz, Birgit; Hetterich, Urban

    2016-07-01

    The avoidance of wheat, gluten and other cereal products is a growing phenomenon in industrialized countries. The diagnostic criteria of celiac disease and of food allergy to wheat flour and/or other cereals are clearly defined. Only about 0.5-25 % of the population are affected from both of these immunological diseases.Nevertheless, there exists a significantly greater proportion of people reporting at least subjectively significant complaints and quality of life improvements after switching to a wheat- or gluten-free diet. Celiac disease or wheat allergy cannot be detected in these individuals on the basis of established criteria. The absence of clear diagnostic autoimmune or allergic criteria in these wheat sensitive patients has resulted in the description of non-celiac gluten sensitivity.It is clinically detectable in only very few individuals and may manifest with either intestinal, extra-intestinal or neurovegetative and psychosomatic symptoms, respectively. However, non-celiac disease gluten sensitivity has to be differentiated critically from irritable bowel syndrome, carbohydrate malassimilation, postinfectious conditions and psychosomatic diseases.Pathophysiologically, non-celiac disease gluten sensitivity is still poorly characterized; several non-immunological mechanisms are discussed to contribute to non-celiac gluten sensitivity. These include the effects of fructo- and galacto-oligosaccharides, of trypsin inhibitors of amylase, and wheat lectin agglutinins, which may influence or modulate intestinal permeability and/or a non-specific immune or effector cell degranulation within the gastrointestinal tract. In addition, further metabolic effects with direct or indirect influence on the intestinal flora are currently discussed.In addition to subjectively reported changes in symptoms that may affect variably intestinal, as well as extra-intestinal and/or neuropsychiatric symptoms, some studies suggest that there is little reproducibility of

  18. Inhaled birch pollen extract induces airway hyperresponsiveness via oxidative stress but independently of pollen-intrinsic NADPH oxidase activity, or the TLR4-TRIF pathway.

    PubMed

    Shalaby, Karim H; Allard-Coutu, Alexandra; O'Sullivan, Michael J; Nakada, Emily; Qureshi, Salman T; Day, Brian J; Martin, James G

    2013-07-15

    Oxidative stress in allergic asthma may result from oxidase activity or proinflammatory molecules in pollens. Signaling via TLR4 and its adaptor Toll-IL-1R domain-containing adapter inducing IFN-β (TRIF) has been implicated in reactive oxygen species-mediated acute lung injury and in Th2 immune responses. We investigated the contributions of oxidative stress and TLR4/TRIF signaling to experimental asthma induced by birch pollen exposure exclusively via the airways. Mice were exposed to native or heat-inactivated white birch pollen extract (BPEx) intratracheally and injected with the antioxidants, N-acetyl-L-cysteine or dimethylthiourea, prior to sensitization, challenge, or all allergen exposures, to assess the role of oxidative stress and pollen-intrinsic NADPH oxidase activity in allergic sensitization, inflammation, and airway hyperresponsiveness (AHR). Additionally, TLR4 signaling was antagonized concomitantly with allergen exposure, or the development of allergic airway disease was evaluated in TLR4 or TRIF knockout mice. N-acetyl-L-cysteine inhibited BPEx-induced eosinophilic airway inflammation and AHR except when given exclusively during sensitization, whereas dimethylthiourea was inhibitory even when administered with the sensitization alone. Heat inactivation of BPEx had no effect on the development of allergic airway disease. Oxidative stress-mediated AHR was also TLR4 and TRIF independent; however, TLR4 deficiency decreased, whereas TRIF deficiency increased BPEx-induced airway inflammation. In conclusion, oxidative stress plays a significant role in allergic sensitization to pollen via the airway mucosa, but the pollen-intrinsic NADPH oxidase activity and TLR4 or TRIF signaling are unnecessary for the induction of allergic airway disease and AHR. Pollen extract does, however, activate TLR4, thereby enhancing airway inflammation, which is restrained by the TRIF-dependent pathway.

  19. Association of allergic sensitization with infectious diseases burden in Roma and non-Roma children.

    PubMed

    Michos, Athanasios; Terzidis, Agis; Kanariou, Maria; Kalampoki, Vasiliki; Koilia, Christina; Giannaki, Maria; Liatsis, Manolis; Pangalis, Anastasia; Petridou, Eleni

    2011-03-01

    The hypothesis whether exposure to certain infections protects from atopy remains equivocal. To further investigate this, we compared serologic markers of infection and allergic sensitization prevalence in Roma children, who live under unfavorable hygienic conditions that facilitate the spread of infections, and non-Roma children who live in the same area. Analyses included 98 Roma and 118 non-Roma children. Serum IgG antibodies for 13 foodborne- airborne- and bloodborne infectious agents were determined, and a cumulative index of exposure was calculated by adding one point for each positive infection. Specific serum IgE to certain common food- and aero-allergens was also tested. and positivity to any of them was defined as indication of atopy. Roma children were found significantly more seropositive for T. gondii, Hepatitis A, H. pylori, HSV-1, CMV, and Hepatitis B (p < 0.0001). Non-Roma children were found more seropositive for RSV and M. pneumonia (p < 0.0001). Regarding the overall prevalence of atopy or the specific IgE responses to the allergens tested, no statistically significant differences were found between Roma and non-Roma children. A positive association of the cumulative index of exposure to infections with atopy was found in the non-Roma children (OR: 1.38, 95% CI: 1.08-1.75, p = 0.01) and in the total population (OR: 1.42, 95% CI: 1.11-1.83, p = 0.01). Regarding the specific infectious agents tested, a statistically significant positive association of atopy with seropositivity was found for M. pneumoniae in the non-Roma children (OR: 3.93, 95% CI: 1.39) as well as in the total population studied (OR: 2.83, 95% CI: 1.32-6.07, p = 0.01). Despite the higher burden of exposure to the battery of the infectious agents tested among Roma children, no protective effect for allergic disease development was evident. On the contrary, a positive association of exposure to infections with evidence of atopy was found, especially evident in the non-Roma children.

  20. Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

    PubMed

    Yi, E S; Lee, H; Suh, Y K; Tang, W; Qi, M; Yin, S; Remick, D G; Ulich, T R

    1996-10-01

    Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations. PMID:8863677

  1. Broncho-Vaxom Attenuates Allergic Airway Inflammation by Restoring GSK3β-Related T Regulatory Cell Insufficiency

    PubMed Central

    Zhong, Hua; Yu, Dehong; Zeng, Xianping; Deng, Mengxia; Sun, Yueqi; Wen, Weiping; Li, Huabin

    2014-01-01

    Background Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV)) has been proposed to attenuate asthma through modulating Treg cells. However, the underlying mechanism has not been fully characterized. This study sought to assess the effects of oral administration of BV on GSK-3β expression and Treg cells in ovalbumin (OVA)-induced asthmatic mice models. Method Asthmatic mice models were established with OVA challenge and treated with oral administration of BV. Next, infiltration of inflammatory cells including eosinophil and neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and expression of GSK3β and Foxp3 were examined in asthmatic mice models by histological analysis, Bio-Plex and western blot, respectively. Moreover, the frequencies of Treg cells were evaluated in cultured splenocytes by flow cytometry in the presence of BV or GSK3β siRNA interference. Results We found significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage fluid (BALF) in asthmatic mice models after oral administration of BV. Oral administration of BV was shown to significantly suppress mucus metaplasia, Th2-typed cytokine levels and GSK3β expression while increasing Foxp3 production in asthmatic mice models. Moreover, BV significantly enhanced GSK3β-related expansion of Treg cells in cultured spleen cells in vitro. Conclusion Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3β-related expansion of Treg cells. PMID:24667347

  2. Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.

    PubMed

    Dong, Caroline C; Yin, Xuejun J; Ma, Jane Y C; Millecchia, Lyndell; Barger, Mark W; Roberts, Jenny R; Zhang, Xing-Dong; Antonini, James M; Ma, Joseph K H

    2005-11-01

    Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway

  3. DIESEL PARTICLE INSTILLATION ENHANCES INFLAMMATORY AND NEUROTROPHIN RESPONSES IN THE LUNGS OF ALLERGIC BALB/C MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airways resistance and inflammation. Antibody blockade of NGF attenuates airways resistance associated with the allergen-specific airways responses in mice. ...

  4. Interaction of ozone exposure with airway hyperresponsiveness and inflammation induced by trimellitic anhydride in sensitized guinea pigs

    SciTech Connect

    Sun, Jian; Chung, K.Fan

    1997-09-01

    The effect of prior ozone (O{sub 3}) exposure on airway hyperresponsiveness and inflammation induced by trimellitic anhydride (TMA) has been investigated in TMA-sensitized guinea pigs. Airway responsiveness was measured as the concentration of acetylcholine needed to increase baseline lung resistance (RL) by 300% (PC300). Ozone (3 ppm, for 3 h) caused an increase in-log PC300 at 1 h after exposure, with return of -log PC300 to control levels at 8 h. Ozone also increased baseline RL at 8 h. TMA challenge increase -log PC300 in TMA-sensitized guinea pigs at 8 h after challenge from 3.85 {+-} 0.09 to 4.11 {+-} 0.09. Ozone exposure prior to TMA challenge prevented the induction of airway hyperresponsiveness with a mean -log PC300 of 3.51 {+-} 0.20, which was not different from that of control TMA-Sensitized group. Baseline RL was significantly higher in ozone-pretreated animals after TMA challenge when compared to those of either control or challenged with TMA alone. Ozone had no effect on TMA challenge-induced BAL eosinophilia and neutrophilia. We conclude that a single exposure to ozone inhibits the increase in airway responsiveness, but increases the bronchoconstrictor response induced by TMA in TMA-Sensitized guinea pigs; however, the inflammatory airway response to TMA is unchanged by preexposure to ozone. 29 refs., 2 figs., 1 tab.

  5. Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

    PubMed Central

    Lee, L Y; Widdicombe, J G

    2001-01-01

    Bronchopulmonary C-fiber endings and rapidly adapting pulmonary receptors (RARs) are primarily responsible for eliciting the defense reflexes in protecting the lungs against inhaled irritants. In anesthetized animals, inhalation of cigarette smoke, one of the common inhaled irritants, into the lungs elicits pulmonary chemoreflexes that are mediated through the stimulation of pulmonary C fibers. When the C-fiber conduction is selectively blocked in the vagus nerves, the same smoke inhalation triggered only augmented breaths, a reflex effect of activating RARs, in the same animals. Indeed, electrophysiologic study shows that inhaled smoke exerts a direct stimulatory effect on both types of afferents. Increasing evidence indicates that the excitability of these afferents and therefore their reflex actions are enhanced by airway mucosal inflammation; one such example is the airway hyperresponsiveness induced by acute exposure to ozone. Although the mechanism underlying the inflammation-induced hypersensitivity of C-fiber endings is not fully understood, the possible involvement of local release of certain inflammatory mediators, such as histamine and prostaglandin E(2) (PGE(2), should be considered. It is believed that changes in the membrane properties mediated by the activation of certain specific receptor proteins located on the membrane of these nerve terminals are involved, as the sensitizing effects of PGE(2) can be also demonstrated in cultured pulmonary C neurons. PMID:11544168

  6. Airway epithelial NF-κB activation promotes the ability to overcome inhalational antigen tolerance

    PubMed Central

    Ather, Jennifer L.; Foley, Kathryn L.; Suratt, Benjamin T.; Boyson, Jonathan E.; Poynter, Matthew E.

    2015-01-01

    Background Inhalational antigen tolerance typically protects against the development of allergic airway disease but may be overcome to induce allergic sensitization preceding the development of asthma. Objectives We examined in vivo whether pre-existing inhalational antigen tolerance could be overcome by activation of the transcription factor NF-κB in conducting airway epithelial cells, and used a combination of in vivo and in vitro approaches to examine the mechanisms involved. Methods Wildtype and transgenic mice capable of expressing constitutively active IκB kinase β (CAIKKβ) in airway epithelium were tolerized to inhaled ovalbumin. Twenty-eight days later, the transgene was transiently expressed and mice were exposed to inhaled OVA on day 30 in an attempt to overcome inhalational tolerance. Results Following ovalbumin challenge on days 40-42, CAIKKβ mice in which the transgene had been activated exhibited characteristic features of allergic airway disease, including airway eosinophilia and methacholine hyperresponsiveness. Increases in the CD103+ and CD11bHI lung dendritic cell populations were present in CAIKKβ mice on day 31. Bronchoalveolar lavage from mice expressing CAIKKβ mice induced CD4+ T cells to secrete TH2 and TH17 cytokines, an effect that required IL-4 and IL-1 signaling, respectively. CAIKKβ mice on Dox demonstrated increased numbers of innate lymphoid type 2 cells (ILC2) in the lung, which also exhibited elevated mRNA expression of the TH2-polarizing cytokine IL-4. Finally, airway epithelial NF-kB activation induced allergic sensitization in CAIKKβ mice on Dox that required IL-4 and IL-1-signaling in vivo. Conclusions Our studies demonstrate that soluble mediators generated in response to airway epithelial NF-κB activation orchestrate the breaking of inhalational tolerance and allergic antigen sensitization through the effects of soluble mediators, including IL-1 and IL-4, on pulmonary dendritic cells as well as innate lymphoid and CD

  7. Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

    PubMed Central

    Yi, E. S.; Lee, H.; Suh, Y. K.; Tang, W.; Qi, M.; Yin, S.; Remick, D. G.; Ulich, T. R.

    1996-01-01

    Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 11 Figure 13 Figure 12 Figure 14 PMID:8863677

  8. Effect of Amino Acid Polymorphisms of House Dust Mite Der p 2 Variants on Allergic Sensitization

    PubMed Central

    Tanyaratsrisakul, Sasipa; Jirapongsananuruk, Orathai; Kulwanich, Bhakkawarat; Hales, Belinda J.; Thomas, Wayne R.

    2016-01-01

    Purpose The sequence variations of the Der p 2 allergen of Dermatophagoides pteronyssinus diverge along 2 pathways with particular amino acid substitutions at positions 40,47,111, and 114. The environmental prevalence and IgE binding to Der p 2 variants differ among regions. To compare IgE binding to Der p 2 variants between sera from Bangkok, Thailand and Perth, Western Australia with different variants and to determine the variant-specificity of antibodies induced by vaccination with recombinant variants. Methods The structures of recombinant variants produced in yeast were compared by circular dichroism and 1-anilinonaphthalene 8-sulfonic acid staining of their lipid-binding cavity. Sera from subjects in Bangkok and Perth where different variants are found were compared by the affinity (IC50) of IgE cross-reactivity to different variants and by direct IgE binding. Mice were immunized with the variants Der p 2.0101 and Der p 2.0110, and their IgG binding to Der p 2.0103, 2.0104, and 2.0109 was measured. Results The secondary structures of the recombinant variants resembled the natural allergen but with differences in ANS binding. The IC50 of Der p 2.0101 required 7-fold higher concentrations to inhibit IgE binding to the high-IgE-binding Der p 2.0104 than for homologous inhibition in sera from Bangkok where it is absent, while in sera from Perth that have both variants the IC50 was the same and low. Reciprocal results were obtained for Der p 2.0110 not found in Perth. Direct binding revealed that Der p 2.0104 was best for detecting IgE in both regions, followed by Der p 2.0101 with binding to other variants showing larger differences. Mouse anti-Der p 2.0101 antibodies had a high affinity of cross-reactivity but bound poorly to other variants. Conclusions The affinity of IgE antibody cross-reactivity, the direct IgE binding, and the specificities of antibodies induced by vaccination show that measures of allergic sensitization and therapeutic strategies could be

  9. Focus on cat allergen (Fel d 1): immunological and aerodynamic characteristics, modality of airway sensitization and avoidance strategies.

    PubMed

    Liccardi, Gennaro; D'Amato, Gennaro; Russo, Maria; Canonica, Giorgio Walter; D'Amato, Luciana; De Martino, Mariano; Passalacqua, Giovanni

    2003-09-01

    The increasing frequency of pet ownership (especially cats) in many industrialized countries has raised the level of exposure to the allergens produced by these animals. Moreover, it is likely that modern energy-saving systems and the wide use of upholstered furniture has resulted in closer contact between cats (and their allergens) and humans. Many different methods have been developed to quantify the main cat allergen (Fel d 1) in settled dust and in ambient air. The threshold levels of cat allergen inducing sensitization or triggering respiratory symptoms in sensitized patients have been calculated in settled dust, but airborne amounts of Fel d 1 probably represent a more reliable index of allergen exposure. Noticeably, the amount of Fel d 1 may be relatively high also in confined environments where cats have never been kept. It has been demonstrated that clothes of cat owners are the main source for dispersal of allergens in cat-free environments. This fact may be of relevance, because recent studies have shown that allergic sensitization to cats is more likely to develop in children exposed to moderate levels of this allergen than in children exposed to high amounts of Fel d 1. The ubiquity of cat allergen may justify the common observation that allergen avoidance is often insufficient to reduce the risk of developing allergic sensitization and/or symptom exacerbation in highly susceptible patients. Further efforts are needed to improve the efficacy of Fel d 1 avoidance strategies to try to reduce the risk of allergic sensitization to this allergen.

  10. SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE

    EPA Science Inventory

    SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE. D. M. Brass, J. D. Savov, *S. H. Gavett, ?C. George, D. A. Schwartz. Duke Univ Medical Center Durham, NC, *U.S. E.P.A. Research Triangle Park, NC, ?Univ of Iowa,...

  11. Does traffic exhaust contribute to the development of asthma and allergic sensitization in children: findings from recent cohort studies

    PubMed Central

    2009-01-01

    The aim of this review was to assess the evidence from recent prospective studies that long-term traffic pollution could contribute to the development of asthma-like symptoms and allergic sensitization in children. We have reviewed cohort studies published since 2002 and found in PubMed in Oct 2008. In all, 13 papers based on data from 9 cohorts have evaluated the relationship between traffic exposure and respiratory health. All surveys reported associations with at least some of the studied respiratory symptoms. The outcome varied, however, according to the age of the child. Nevertheless, the consistency in the results indicates that traffic exhaust contributes to the development of respiratory symptoms in healthy children. Potential effects of traffic exhaust on the development of allergic sensitization were only assessed in the four European birth cohorts. Long-term exposure to outdoor air pollutants had no association with sensitization in ten-year-old schoolchildren in Norway. In contrast, German, Dutch and Swedish preschool children had an increased risk of sensitization related to traffic exhaust despite fairly similar levels of outdoor air pollution as in Norway. Traffic-related effects on sensitization could be restricted to individuals with a specific genetic polymorphism. Assessment of gene-environment interactions on sensitization has so far only been carried out in a subgroup of the Swedish birth cohort. Further genetic association studies are required and may identify individuals vulnerable to adverse effects from traffic-related pollutants. Future studies should also evaluate effects of traffic exhaust on the development and long term outcome of different phenotypes of asthma and wheezing symptoms. PMID:19371435

  12. Kaempferol Inhibits Endoplasmic Reticulum Stress-Associated Mucus Hypersecretion in Airway Epithelial Cells And Ovalbumin-Sensitized Mice

    PubMed Central

    Choi, Yean-Jung; Kang, Min-Kyung; Kim, Yun-Ho; Kang, Young-Hee

    2015-01-01

    Mucus hypersecretion is an important pathological feature of chronic airway diseases, such as asthma and pulmonary diseases. MUC5AC is a major component of the mucus matrix forming family of mucins in the airways. The initiation of endoplasmic reticulum (ER)-mediated stress responses contributes to the pathogenesis of airway diseases. The present study investigated that ER stress was responsible for airway mucus production and this effect was blocked by the flavonoid kaempferol. Oral administration of ≥10 mg/kg kaempferol suppressed mucus secretion and goblet cell hyperplasia observed in the bronchial airway and lung of BALB/c mice sensitized with ovalbumin (OVA). TGF-β and tunicamycin promoted MUC5AC induction after 72 h in human bronchial airway epithelial BEAS-2B cells, which was dampened by 20 μM kaempferol. Kaempferol inhibited tunicamycin-induced ER stress of airway epithelial cells through disturbing the activation of the ER transmembrane sensor ATF6 and IRE1α. Additionally, this compound demoted the induction of ER chaperones such as GRP78 and HSP70 and the splicing of XBP-1 mRNA by tunicamycin. The in vivo study further revealed that kaempferol attenuated the induction of XBP-1 and IRE1α in epithelial tissues of OVA-challenged mice. TGF-β and tunicamycin induced TRAF2 with JNK activation and such induction was deterred by kaempferol. The inhibition of JNK activation encumbered the XBP-1 mRNA splicing and MUC5AC induction by tunicamycin and TGF-β. These results demonstrate that kaempferol alleviated asthmatic mucus hypersecretion through blocking bronchial epithelial ER stress via the inhibition of IRE1α-TRAF2-JNK activation. Therefore, kaempferol may be a potential therapeutic agent targeting mucus hypersecretion-associated pulmonary diseases. PMID:26599511

  13. Influenza A infection enhances antigen-induced airway inflammation and hyper-responsiveness in young but not aged mice

    PubMed Central

    Birmingham, Janette M.; Gillespie, Virginia L.; Srivastava, Kamal; Li, Xiu-Min; Busse, Paula J.

    2015-01-01

    Background Although morbidity and mortality rates from asthma are highest in patients > 65 years of age, the effect of older age on airway inflammation in asthma is not well established. Objective To investigate age-related differences in the promotion of allergic inflammation after influenza A viral respiratory infection on antigen specific IgE production, antigen-induced airway inflammation and airway hyper-responsiveness in mice. Methods To accomplish this objective, the following model system was used. Young (six-week) and aged (18-month) BALB/c mice were first infected with a non-lethal dose of influenza virus A (H/HK×31). Mice were then ovalbumin (OVA) sensitized during the acute-infection (3-days post inoculation) and then chronically underwent challenge to the airways with OVA. Forty-eight hours after the final OVA-challenge, airway hyperresponsiveness (AHR), bronchoalveolar fluid (BALF) cellular and cytokine profile, antigen-specific IgE and IgG1, and lung tissue inflammation were measured. Results Age-specific differences were noted on the effect of a viral infection, allergic sensitization, airway inflammation and airway hyperresponsiveness. Serum OVA-specific IgE was significantly increased in only the aged mice infected with influenza virus. Despite greater morbidity (e.g. weight loss and sickness scores) during the acute infection in the 18-month old mice that were OVA-sensitized there was little effect on the AHR and BALF cellular differential. In contrast, BALF neutrophils and AHR increased, but eosinophils decreased in 6-week mice that were OVA-sensitized during an acute influenza infection. Conclusion With increased age in a mouse model, viral infection prior to antigen sensitization affects the airway and systemic allergic response differently. These differences may reflect distinct phenotypic features of allergic inflammation in older patients with asthma PMID:25039815

  14. Airway Surface Mycosis in Chronic Th2-Associated Airway Disease

    PubMed Central

    Porter, Paul; Lim, Dae Jun; Maskatia, Zahida Khan; Mak, Garbo; Tsai, Chu-Lin; Citardi, Martin J; Fakhri, Samer; Shaw, Joanne L.; Fothergil, Annette; Kheradmand, Farrah; Corry, David B; Luong, Amber

    2014-01-01

    Background Environmental fungi have been linked to T helper type 2 (Th2) cell-related airway inflammation and the Th2-associated chronic airway diseases asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in Th2-associated and non-associated airway disease patients. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n=118) including CRS patients with and without nasal polyps and AFRS and non-CRS/non-asthmatic control patients. Asthma status was deteremined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. Peripheral blood mononuclear cells were restimulated with fungal antigens in an enzyme linked immunocell spot (ELISpot) assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared to fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured from Th2-associated airway disease subjects (asthma, CRSwNP, or AFRS: n=68) compared to non-Th2-associated control patients (n=31); 74% vs 16% respectively, p<0.001. Both fungus-specific IL-4 ELISpot (n=48) and specific IgE (n=70) data correlated with Th2-associated diseases (sensitivity 73% and specificity 100% vs. 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with Th2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Clinical Implications Airway fungi may contribute to the expression of sinusitis with nasal polyps and

  15. Environmental risk factors and allergic bronchial asthma.

    PubMed

    D'Amato, G; Liccardi, G; D'Amato, M; Holgate, S

    2005-09-01

    The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic

  16. Environmental risk factors and allergic bronchial asthma.

    PubMed

    D'Amato, G; Liccardi, G; D'Amato, M; Holgate, S

    2005-09-01

    The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic

  17. Allergic rhinitis

    MedlinePlus

    ... allergic to, such as dust, animal dander, or pollen. Symptoms can also occur when you eat a ... article focuses on allergic rhinitis due to plant pollens. This type of allergic rhinitis is commonly called ...

  18. Characteristics of Allergic Pulmonary Inflammation in CXCR3Knockout Mice Sensitized and Challenged with House Dust Mite Protein

    PubMed Central

    Chen, Xiaolan; Gao, Jinming; Guo, Zijian

    2016-01-01

    Chemokine C-X-C motif receptor 3 (CXCR3) is a chemokine receptor that is mainly expressed by activated T lymphocytes. T cells play important roles in allergic pulmonary inflammation, which is a hallmark of asthma and elicits the localized accumulation of activated T cells in the lung. In China, a marked increase in the incidence rate of chronic allergic pulmonary inflammation has made it a major public health threat. In the present study, we investigated the role of CXCR3 and its ligands in airway inflammation induced by house dust mite protein (HDMP) in a CXCR3 knockout (CXCR3KO) asthma mouse model. Pathological manifestations in the lung, cell counts and bronchoalveolar lavage fluid (BALF) classifications were studied using hematoxylin and eosin (H&E) staining. The levels of IL-4 and IFN-γ in the BALF and splenocyte supernatants were measured using ELISA. CD4+ and CD8+ T cells in the lung and spleen were analyzed by flow cytometry. RT-PCR was applied to measure the mRNA transcript levels of monokines induced by IFN-γ(CXCL9) and IFN-γ inducible protein 10(CXCL10). The total cell counts, eosinophil counts, and IL-4 levels in the BALF and cultured splenocyte supernatants were significantly increased, while the levels of IFN-γ were reduced in the HDMP groups(P<0.01). Changes in the total cell counts, eosinophil counts, and lymphocyte counts, as well as the total protein levels in the BALF, the levels of IL-4 in splenocyte supernatants, and the pathological manifestations in the lung, were all greater in CXCR3KO mice than in C57BL/6 wild-type mice. Furthermore, the expression levels of CXCL9 and CXCL10 mRNA transcripts in the lungs of CXCR3KO mice were lower than those in C57BL/6 wild-type mice (P<0.05). CXCR3 and its ligands (i.e., CXCL9 and CXCL10) may play anti-inflammatory roles in this animal model. Promoting the expression of CXCR3 and its ligands may represent a novel therapeutic approach for preventing and curing asthma. PMID:27727269

  19. Skin prick testing predicts peanut challenge outcome in previously allergic or sensitized children with low serum peanut-specific IgE antibody concentration.

    PubMed

    Nolan, Richard C; Richmond, Peter; Prescott, Susan L; Mallon, Dominic F; Gong, Grace; Franzmann, Annkathrin M; Naidoo, Rama; Loh, Richard K S

    2007-05-01

    Peanut allergy is transient in some children but it is not clear whether quantitating peanut-specific IgE by Skin Prick Test (SPT) adds additional information to fluorescent-enzyme immunoassay (FEIA) in discriminating between allergic and tolerant children. To investigate whether SPT with a commercial extract or fresh foods adds additional predictive information for peanut challenge in children with a low FEIA (<10 k UA/L) who were previously sensitized, or allergic to peanuts. Children from a hospital-based allergy service who were previously sensitized or allergic to peanuts were invited to undergo a peanut challenge unless they had a serum peanut-specific IgE>10 k UA/L, a previous severe reaction, or a recent reaction to peanuts (within two years). SPT with a commercial extract, raw and roasted saline soaked peanuts was performed immediately prior to open challenge in hospital with increasing quantity of peanuts until total of 26.7 g of peanut was consumed. A positive challenge consisted of an objective IgE mediated reaction occurring during the observation period. 54 children (median age of 6.3 years) were admitted for a challenge. Nineteen challenges were positive, 27 negative, five were indeterminate and three did not proceed after SPT. Commercial and fresh food extracts provided similar diagnostic information. A wheal diameter of >or=7 mm of the commercial extract predicted an allergic outcome with specificity 97%, positive predictive value 93% and sensitivity 83%. There was a tendency for an increase in SPT wheal since initial diagnosis in children who remained allergic to peanuts while it decreased in those with a negative challenge. The outcome of a peanut challenge in peanut sensitized or previously allergic children with a low FEIA can be predicted by SPT. In this cohort, not challenging children with a SPT wheal of >or=7 mm would have avoided 15 of 18 positive challenges and denied a challenge to one out of 27 tolerant children.

  20. Outdoor air pollution in urban areas and allergic respiratory diseases.

    PubMed

    D'Amato, G

    1999-12-01

    Respiratory allergic diseases (rhinitis, rhinosinusitis, bronchial asthma and its equivalents) appear to be increasing in most countries, and subjects living in urban and industrialized areas are more likely to experience respiratory allergic symptoms than those living in rural areas. This increase has been linked, among various factors, to air pollution, which is now an important public health hazard. Laboratory studies confirm the epidemiological evidence that inhalation of some pollutants, either individually or in combination, adversely affect lung function in asthmatics. The most abundant air pollutants in urban areas with high levels of vehicle traffic are respirable particulate matter, nitrogen dioxide and ozone. While nitrogen dioxide does not exert consistent effects on lung function, ozone, respirable particulate matter and allergens impair lung function and lead to increased airway responsiveness and bronchial obstruction in predisposed subjects. However, besides acting as irritants, airborne pollutants can modulate the allergenicity of antigens carried by airborne particles. By attaching to the surface of pollen grains and of plant-derived paucimicronic particles, pollutants can modify the morphology of these antigen-carrying agents and after their allergenic potential. In addition, by inducing airway inflammation, which increases airway epithelial permeability, pollutants overcome the mucosal barrier and so facilitate the allergen-induced inflammatory responses. Moreover, air pollutants such as diesel exhaust emissions are thought to modulate the immune response by increasing immunoglobulin E synthesis, thus facilitating allergic sensitization in atopic subjects and the subsequent development of clinical respiratory symptoms. PMID:10695313

  1. Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice.

    PubMed

    Duong, Khang M; Arikkatt, Jaisy; Ullah, M Ashik; Lynch, Jason P; Zhang, Vivian; Atkinson, Kerry; Sly, Peter D; Phipps, Simon

    2015-11-01

    Allergic asthma is underpinned by T helper 2 (Th2) inflammation. Redundancy in Th2 cytokine function and production by innate and adaptive immune cells suggests that strategies aimed at immunomodulation may prove more beneficial. Hence, we sought to determine whether administration of mesenchymal stromal cells (MSCs) to house dust mite (HDM) (Dermatophagoides pteronyssinus)-sensitized mice would suppress the development of Th2 inflammation and airway hyperresponsiveness (AHR) after HDM challenge. We report that the intravenous administration of allogeneic donor MSCs 1 hour before allergen challenge significantly attenuated the features of allergic asthma, including tissue eosinophilia, Th2 cytokine (IL-5 and IL-13) levels in bronchoalveolar lavage fluid, and AHR. The number of infiltrating type 2 innate lymphoid cells was not affected by MSC transfer, suggesting that MSCs may modulate the adaptive arm of Th2 immunity. The effect of MSC administration was long lasting; all features of allergic airway disease were significantly suppressed in response to a second round of HDM challenge 4 weeks after MSC administration. Further, we observed that MSCs decreased the release of epithelial cell-derived alarmins IL-1α and high mobility group box-1 in an IL-1 receptor antagonist-dependent manner. This significantly decreased the expression of the pro-Th2 cytokine IL-25 and reduced the number of activated and antigen-acquiring CD11c(+)CD11b(+) dendritic cells in the lung and mediastinal lymph nodes. Our findings suggest that MSC administration can ameliorate allergic airway inflammation by blunting the amplification of epithelial-derived inflammatory cytokines induced by HDM exposure and may offer long-term protection against Th2-mediated allergic airway inflammation and AHR.

  2. Development of a regional-scale pollen emission and transport modeling framework for investigating the impact of climate change on allergic airway disease

    NASA Astrophysics Data System (ADS)

    Zhang, R.; Duhl, T.; Salam, M. T.; House, J. M.; Flagan, R. C.; Avol, E. L.; Gilliland, F. D.; Guenther, A.; Chung, S. H.; Lamb, B. K.; VanReken, T. M.

    2014-03-01

    Exposure to bioaerosol allergens such as pollen can cause exacerbations of allergenic airway disease (AAD) in sensitive populations, and thus cause serious public health problems. Assessing these health impacts by linking the airborne pollen levels, concentrations of respirable allergenic material, and human allergenic response under current and future climate conditions is a key step toward developing preventive and adaptive actions. To that end, a regional-scale pollen emission and transport modeling framework was developed that treats allergenic pollens as non-reactive tracers within the coupled Weather Research and Forecasting Community Multiscale Air Quality (WRF/CMAQ) modeling system. The Simulator of the Timing and Magnitude of Pollen Season (STaMPS) model was used to generate a daily pollen pool that can then be emitted into the atmosphere by wind. The STaMPS is driven by species-specific meteorological (temperature and/or precipitation) threshold conditions and is designed to be flexible with respect to its representation of vegetation species and plant functional types (PFTs). The hourly pollen emission flux was parameterized by considering the pollen pool, friction velocity, and wind threshold values. The dry deposition velocity of each species of pollen was estimated based on pollen grain size and density. An evaluation of the pollen modeling framework was conducted for southern California (USA) for the period from March to June 2010. This period coincided with observations by the University of Southern California's Children's Health Study (CHS), which included O3, PM2.5, and pollen count, as well as measurements of exhaled nitric oxide in study participants. Two nesting domains with horizontal resolutions of 12 and 4 km were constructed, and six representative allergenic pollen genera were included: birch tree, walnut tree, mulberry tree, olive tree, oak tree, and brome grasses. Under the current parameterization scheme, the modeling framework tends to

  3. Development of a regional-scale pollen emission and transport modeling framework for investigating the impact of climate change on allergic airway disease

    NASA Astrophysics Data System (ADS)

    Zhang, R.; Duhl, T.; Salam, M. T.; House, J. M.; Flagan, R. C.; Avol, E. L.; Gilliland, F. D.; Guenther, A.; Chung, S. H.; Lamb, B. K.; VanReken, T. M.

    2013-03-01

    Exposure to bioaerosol allergens such as pollen can cause exacerbations of allergenic airway disease (AAD) in sensitive populations, and thus cause serious public health problems. Assessing these health impacts by linking the airborne pollen levels, concentrations of respirable allergenic material, and human allergenic response under current and future climate conditions is a key step toward developing preventive and adaptive actions. To that end, a regional-scale pollen emission and transport modeling framework was developed that treats allergenic pollens as non-reactive tracers within the WRF/CMAQ air-quality modeling system. The Simulator of the Timing and Magnitude of Pollen Season (STaMPS) model was used to generate a daily pollen pool that can then be emitted into the atmosphere by wind. The STaMPS is driven by species-specific meteorological (temperature and/or precipitation) threshold conditions and is designed to be flexible with respect to its representation vegetation species and plant functional types (PFTs). The hourly pollen emission flux was parameterized by considering the pollen pool, friction velocity, and wind threshold values. The dry deposition velocity of each species of pollen was estimated based on pollen grain size and density. An evaluation of the pollen modeling framework was conducted for southern California for the period from March to June 2010. This period coincided with observations by the University of Southern California's Children's Health Study (CHS), which included O3, PM2.5, and pollen count, as well as measurements of exhaled nitric oxide in study participants. Two nesting domains with horizontal resolutions of 12 km and 4 km were constructed, and six representative allergenic pollen genera were included: birch tree, walnut tree, mulberry tree, olive tree, oak tree, and brome grasses. Under the current parameterization scheme, the modeling framework tends to underestimate walnut and peak oak pollen concentrations, and tends to

  4. Development of a regional-scale pollen emission and transport modeling framework for investigating the impact of climate change on allergic airway disease.

    PubMed

    Zhang, Rui; Duhl, Tiffany; Salam, Muhammad T; House, James M; Flagan, Richard C; Avol, Edward L; Gilliland, Frank D; Guenther, Alex; Chung, Serena H; Lamb, Brian K; VanReken, Timothy M

    2013-03-01

    Exposure to bioaerosol allergens such as pollen can cause exacerbations of allergenic airway disease (AAD) in sensitive populations, and thus cause serious public health problems. Assessing these health impacts by linking the airborne pollen levels, concentrations of respirable allergenic material, and human allergenic response under current and future climate conditions is a key step toward developing preventive and adaptive actions. To that end, a regional-scale pollen emission and transport modeling framework was developed that treats allergenic pollens as non-reactive tracers within the WRF/CMAQ air-quality modeling system. The Simulator of the Timing and Magnitude of Pollen Season (STaMPS) model was used to generate a daily pollen pool that can then be emitted into the atmosphere by wind. The STaMPS is driven by species-specific meteorological (temperature and/or precipitation) threshold conditions and is designed to be flexible with respect to its representation of vegetation species and plant functional types (PFTs). The hourly pollen emission flux was parameterized by considering the pollen pool, friction velocity, and wind threshold values. The dry deposition velocity of each species of pollen was estimated based on pollen grain size and density. An evaluation of the pollen modeling framework was conducted for southern California for the period from March to June 2010. This period coincided with observations by the University of Southern California's Children's Health Study (CHS), which included O3, PM2.5, and pollen count, as well as measurements of exhaled nitric oxide in study participants. Two nesting domains with horizontal resolutions of 12 km and 4 km were constructed, and six representative allergenic pollen genera were included: birch tree, walnut tree, mulberry tree, olive tree, oak tree, and brome grasses. Under the current parameterization scheme, the modeling framework tends to underestimate walnut and peak oak pollen concentrations, and tends

  5. Resolvin D1 and Resolvin E1 Promote the Resolution of Allergic Airway Inflammation via Shared and Distinct Molecular Counter-Regulatory Pathways

    PubMed Central

    Levy, Bruce D.

    2012-01-01

    Resolvins are generated from omega-3 fatty acids during inflammatory responses in the lung. These natural mediators interact with specific receptors to decrease lung inflammation and promote its resolution in healthy tissues. There are several lung diseases of chronic inflammation that fail to resolve, most notable asthma. This common disorder has a lifetime prevalence of nearly 10% and is characterized, in part, by chronic, non-resolving inflammation of the airway. Pro-resolving mediators are generated during asthma; however, their biosynthesis is decreased in severe and uncontrolled asthma, suggesting that the chronic, adaptive inflammation in asthmatic airways may result from a resolution defect. This article focuses on recent insights into the cellular and molecular mechanisms for resolvins that limit adaptive immune responses in healthy airways. PMID:23293638

  6. Identification of Microcystis aeruginosa Peptides Responsible for Allergic Sensitization and Characterization of Functional Interactions between Cyanobacterial Toxins and Immunogenic Peptides

    PubMed Central

    Geh, Esmond N.; Ghosh, Debajyoti; McKell, Melanie; de la Cruz, Armah A.; Stelma, Gerard

    2015-01-01

    Background The cyanobacterium species Microcystis aeruginosa produces microcystin and an array of diverse metabolites believed responsible for their toxicity and/or immunogenicity. Previously, chronic rhinitis patients were demonstrated to elicit a specific IgE response to nontoxic strains of M. aeruginosa by skin-prick testing, indicating that cyanobacteria allergenicity resides in a non-toxin–producing component of the organism. Objectives We sought to identify and characterize M. aeruginosa peptide(s) responsible for allergic sensitization in susceptible individuals, and we investigated the functional interactions between cyanobacterial toxins and their coexpressed immunogenic peptides. Methods Sera from patients and extracts from M. aeruginosa toxic [MC(+)] and nontoxic [MC(–)] strains were used to test IgE-specific reactivity by direct and indirect ELISAs; 2D gel electrophoresis, followed by immunoblots and mass spectrometry (MS), was performed to identify the relevant sensitizing peptides. Cytotoxicity and mediator release assays were performed using the MC(+) and MC(–) lysates. Results We found specific IgE to be increased more in response to the MC(–) strain than the MC(+) strain. This response was inhibited by preincubation of MC(–) lysate with increasing concentrations of microcystin. MS revealed that phycocyanin and the core-membrane linker peptide are the responsible allergens, and MC(–) extracts containing these proteins induced β-hexosaminidase release in rat basophil leukemia cells. Conclusions Phycobiliprotein complexes in M. aeruginosa have been identified as the relevant sensitizing proteins. Our finding that allergenicity is inhibited in a dose-dependent manner by microcystin toxin suggests that further investigation is warranted to understand the interplay between immunogenicity and toxicity of cyanobacteria under diverse environmental conditions. Citation Geh EN, Ghosh D, McKell M, de la Cruz AA, Stelma G, Bernstein JA. 2015

  7. Allergic reactions (image)

    MedlinePlus

    Allergic reaction is a sensitivity to a specific substance, called an allergen, that is contacted through the skin, inhaled into the lungs, swallowed or injected. The body's reaction to an allergen can be mild, such as ...

  8. NEUROTROPHIN RECEPTOR BLOCKADE ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC RESPONSES

    EPA Science Inventory

    ABSTRACT BODY:
    Recent investigations have linked neurotrophins including NGF, NT-3, and BDNF to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance associated with allergic airway responses in mice. Mice administered an antibody against the low aff...

  9. Airway Defense Control Mediated via Voltage-Gated Sodium Channels.

    PubMed

    Kocmalova, M; Joskova, M; Franova, S; Banovcin, P; Sutovska, M

    2016-01-01

    Expression of voltage-gated sodium channels (Nav) takes place in the airways and the role of Nav1.7 and Nav1.8 in the control of airway's defense reflexes has been confirmed. The activation of Nav channels is crucial for cough initiation and airway smooth muscle reactivity, but it is unknown whether these channels regulate ciliary beating. This study evaluated the involvement of Nav1.7 and Nav1.8 channels in the airway defense mechanisms using their pharmacological blockers in healthy guinea pigs and in the experimental allergic asthma model. Asthma was modeled by ovalbumin sensitization over a period of 21 days. Blockade of Nav1.7 channels significantly decreased airway smooth muscle reactivity in vivo, the number of cough efforts, and the cilia beat frequency in healthy animals. In the allergic asthma model, blockade of Nav1.8 efficiently relieved symptoms of asthma, without adversely affecting cilia beat frequency. The study demonstrates that Nav1.8 channel antagonism has a potential to alleviate cough and bronchial hyperreactivity in asthma. PMID:27161110

  10. Triggers of airway inflammation.

    PubMed

    Kerrebijn, K F

    1986-01-01

    Most asthmatics have hyperresponsive airways. This makes them more sensitive than non-asthmatics to bronchoconstricting environmental exposures which, in their turn, may enhance responsiveness. Airway inflammation is considered to be a key determinant of airway hyperresponsiveness: the fact that chronic airway inflammation in cystic fibrosis does not lead to airway hyperresponsiveness of any importance indicates, however, that the role of airway inflammation is complex and incompletely elucidated. The main inducers of airway inflammation are viral infections, antigens, occupational stimuli and pollutants. Although exercise, airway cooling and hyper- or hypotonic aerosols are potent stimuli of bronchoconstriction, it is questionable if airway inflammation is involved in their mode of action. Each of the above-mentioned stimuli is discussed, with emphasis laid on the relation of symptoms to mechanisms. PMID:3533597

  11. The immune profile associated with acute allergic asthma accelerates clearance of influenza virus

    PubMed Central

    Samarasinghe, Amali E; Woolard, Stacie N; Boyd, Kelli L; Hoselton, Scott A; Schuh, Jane M; McCullers, Jonathan A

    2014-01-01

    Asthma was the most common comorbidity in hospitalized patients during the 2009 influenza pandemic. For unknown reasons, hospitalized asthmatics had less severe outcomes and were less likely to die from pandemic influenza. Our data with primary human bronchial cells indicate that changes intrinsic to epithelial cells in asthma may protect against cytopathology induced by influenza virus. To further study influenza virus pathogenesis in allergic hosts, we aimed to develop and characterize murine models of asthma and influenza comorbidity to determine structural, physiological and immunological changes induced by influenza in the context of asthma. Aspergillus fumigatus-sensitized and -challenged C57BL/6 mice were infected with pandemic H1N1 influenza virus, either during peak allergic inflammation or during airway remodeling to gain insight into disease pathogenesis. Mice infected with the influenza virus during peak allergic inflammation did not lose body weight and cleared the virus rapidly. These mice exhibited high eosinophilia, preserved airway epithelial cell integrity, increased mucus, reduced interferon response and increased insulin-like growth factor-1. In contrast, weight loss and viral replication kinetics in the mice that were infected during the late airway remodeling phase were equivalent to flu-only controls. These mice had neutrophils in the airways, damaged airway epithelial cells, less mucus production, increased interferons and decreased insulin-like growth factor-1. The state of the allergic airways at the time of influenza virus infection alters host responses against the virus. These murine models of asthma and influenza comorbidity may improve our understanding of the epidemiology and pathogenesis of viral infections in humans with asthma. PMID:24469764

  12. IgE cross-reactivity between Ascaris lumbricoides and mite allergens: possible influences on allergic sensitization and asthma.

    PubMed

    Acevedo, N; Caraballo, L

    2011-06-01

    Nematode infections such as Ascariasis are important health problems in underdeveloped countries, most of them located in the tropics where environmental conditions also promote the perennial co-exposure to high concentrations of domestic mite allergens. Allergic diseases are common, and most of patients with asthma exhibit a predominant and strong IgE sensitization to mites. It is unknown whether co-exposure to Ascaris lumbricoides and the domestic mites Blomia tropicalis and Dermatophagoides pteronyssinus potentiates Th2 responses and IgE sensitization, thereby modifying the natural history of allergy. Recently, we obtained experimental evidence of a high cross-reactivity between the allergenic extracts of these invertebrates, involving well-known allergens such as tropomyosin and glutathione transferases. There is indirect evidence suggesting that the clinical impact of these findings may be important. In this review, we discuss the potential role of this cross-reactivity on several aspects of allergy in the tropics that have been a focus of a number of investigations, some of them with controversial results.

  13. Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study

    PubMed Central

    2011-01-01

    Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and

  14. The Effects of Maternal Exposure to Bisphenol A on Allergic Lung Inflammation into Adulthood

    PubMed Central

    Lawrence, B. Paige

    2012-01-01

    Bisphenol A (BPA) is a high–production volume chemical classified as an environmental estrogen and used primarily in the plastics industry. BPA’s increased usage correlates with rising BPA levels in people and a corresponding increase in the incidence of asthma. Due to limited studies, the contribution of maternal BPA exposure to allergic asthma pathogenesis is unclear. Using two established mouse models of allergic asthma, we examined whether developmental exposure to BPA alters hallmarks of allergic lung inflammation in adult offspring. Pregnant C57BL/6 dams were gavaged with 0, 0.5, 5, 50, or 500 μg BPA/kg/day from gestational day 6 until postnatal day 21. To induce allergic inflammation, adult offspring were mucosally sensitized with inhaled ovalbumin containing low-dose lipopolysaccharide or ip sensitized using ovalbumin with alum followed by ovalbumin aerosol challenge. In the mucosal sensitization model, female offspring that were maternally exposed to ≥ 50 μg BPA/kg/day displayed enhanced airway lymphocytic and lung inflammation, compared with offspring of control dams. Peritoneally sensitized, female offspring exposed to ≤ 50 μg BPA/kg/day presented dampened lung eosinophilia, compared with vehicle controls. Male offspring did not exhibit these differences in either sensitization model. Our data demonstrate that maternal exposure to BPA has subtle and qualitatively different effects on allergic inflammation, which are critically dependent upon route of allergen sensitization and sex. However, these subtle, yet persistent changes due to developmental exposure to BPA did not lead to significant differences in overall airway responsiveness, suggesting that early life exposure to BPA does not exacerbate allergic inflammation into adulthood. PMID:22821851

  15. EFFECT OF INHALED ULTRAFINE CARBON PARTICLES ON THE ALLERGIC AIRWAY RESPONSE IN RAGWEED SENSITIZED DOGS. (R826442)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  16. Chlorocresol sensitivity induced by treatment of allergic contact dermatitis with steroid creams.

    PubMed

    Archer, C B; MacDonald, D M

    1984-09-01

    A patient with contact dermatitis from nickel and cobalt developed sensitivity to chlorocresol contained in topical steroid creams. The use of chlorocresol in aqueous creams and topical steroids is reviewed.

  17. Global airway disease beyond allergy.

    PubMed

    Hellings, Peter W; Prokopakis, Emmanuel P

    2010-03-01

    Besides the anatomic continuity of the upper and lower airways, inflammation in one part of the airway influences the homeostasis of the other. The mechanisms underlying this interaction have been studied primarily in allergic disease, showing systemic immune activation, induction of inflammation at a distance, and a negative impact of nasal inflammation on bronchial homeostasis. In addition to allergy, other inflammatory conditions of the upper airways are associated with lower airway disease. Rhinosinusitis is frequently associated with asthma and chronic obstructive pulmonary disease. The impairment of purification, humidification, and warming up of the inspired air by the nose in rhinosinusitis may be responsible in part for bronchial pathology. The resolution of sinonasal inflammation via medical and/or surgical treatment is responsible for the beneficial effect of the treatment on bronchial disease. This article provides a comprehensive overview of the current knowledge of upper and lower airway communication beyond allergic disease.

  18. DIESEL EXHAUST ACTIVATES REDOX-SENSITIVE TRANSCRIPTION FACTORS AND KINASES IN HUMAN AIRWAYS

    EPA Science Inventory

    Diesel exhaust (DE) is a major component of airborne particulate matter. In previous studies we have described the acute inflammatory response of the human airway to inhaled DE. This was characterized by neutrophil, mast cell, and lymphocyte infiltration into the bronchial mucosa...

  19. Regulation of allergic lung inflammation by endothelial cell transglutaminase 2.

    PubMed

    Soveg, Frank; Abdala-Valencia, Hiam; Campbell, Jackson; Morales-Nebreda, Luisa; Mutlu, Gökhan M; Cook-Mills, Joan M

    2015-09-15

    Tissue transglutaminase 2 (TG2) is an enzyme with multiple functions, including catalysis of serotonin conjugation to proteins (serotonylation). Previous research indicates that TG2 expression is upregulated in human asthma and in the lung endothelium of ovalbumin (OVA)-challenged mice. It is not known whether endothelial cell TG2 is required for allergic inflammation. Therefore, to determine whether endothelial cell TG2 regulates allergic inflammation, mice with an endothelial cell-specific deletion of TG2 were generated, and these mice were sensitized and challenged in the airways with OVA. Deletion of TG2 in endothelial cells blocked OVA-induced serotonylation in lung endothelial cells, but not lung epithelial cells. Interestingly, deletion of endothelial TG2 reduced allergen-induced increases in respiratory system resistance, number of eosinophils in the bronchoalveolar lavage, and number of eosinophils in the lung tissue. Endothelial cell deletion of TG2 did not alter expression of adhesion molecules, cytokines, or chemokines that regulate leukocyte recruitment, consistent with other studies, demonstrating that deletion of endothelial cell signals does not alter lung cytokines and chemokines during allergic inflammation. Taken together, the data indicate that endothelial cell TG2 is required for allergic inflammation by regulating the recruitment of eosinophils into OVA-challenged lungs. In summary, TG2 functions as a critical signal for allergic lung responses. These data identify potential novel targets for intervention in allergy/asthma.

  20. Allergic Conjunctivitis

    MedlinePlus

    ... water. This is called conjunctivitis, also known as “pink eye.” Causes & Risk Factors What causes allergic conjunctivitis? ... example, if you are allergic to pollen or mold, stay indoors when pollen and mold levels are ...

  1. The influence of sex, allergic rhinitis, and test system on nasal sensitivity to airborne irritants: a pilot study.

    PubMed

    Shusterman, D; Murphy, M A; Balmes, J

    2001-01-01

    "Nasal irritant sensitivity" is an important construct in environmental health science; functional measures, however, lack standardization. We performed duplicate measures of nasal irritant perceptual acuity on 16 subjects (evenly divided by sex and seasonal allergy status) using two different test compounds: carbon dioxide (CO2) (detection) and n-propanol (localization). The a priori hypotheses included a) allergic rhinitics will display lower perceptual thresholds than nonrhinitics; b) females will display lower perceptual thresholds than males; and c) estimates of perceptual acuity using the two test systems will be positively correlated. We obtained CO2 detection thresholds using an ascending concentration series, presenting 3-sec pulses of CO2, paired with air in random order, by nasal cannula. We obtained localization thresholds by simultaneously presenting stimuli (ascending concentrations of n-propanol vapor in air) and blanks (saturated water vapor in air) to opposite nostrils, with laterality randomized. In terms of test-retest reliability, individual replicate measures for CO2 detection thresholds correlated more closely than did the localization thresholds of volatile organic compounds (VOC) (r = 0.65 and r = 0.60, respectively). As an intertest comparison, log-transformed individual mean CO2 and VOC measures were positively correlated with an r of 0.63 (p < 0.01). In univariate analyses, sex predicted both log-transformed CO2 and VOC thresholds (females being more "sensitive"; p < 0.05 and 0.001, respectively). Nasal allergies predicted sensory testing results only in the multivariate analysis, and then only for VOC localization (p < 0.05). The question of population variation in nasal irritant sensitivity (as well as the generalizability of results across test compounds) deserves further attention. PMID:11171519

  2. Inhibition of Release of Vasoactive and Inflammatory Mediators in Airway and Vascular Tissues and Macrophages By a Chinese Herbal Medicine Formula for Allergic Rhinitis

    PubMed Central

    Li, Chun Guang; Xue, Charlie Changli; Thien, Francis Chung Kong; Story, David Frederick

    2007-01-01

    Herbal therapies are being used increasingly for the treatment of allergic rhinitis. The aim of this study was to investigate the possible pharmacological actions and cellular targets of a Chinese herbal formula (RCM-101), which was previously shown to be effective in reducing seasonal allergic rhinitis symptoms in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated tissues (trachea and aorta) were used to study the effects of RCM-101 on responses to various mediators. Production of leukotriene B4 in porcine neutrophils and of prostaglandin E2 and nitric oxide (NO) in Raw 264.7 cells were also measured. In rat and guinea pig tracheal preparations, RCM-101 inhibited contractile responses to compound 48/80 but not those to histamine (guinea pig preparations) or serotonin (rat preparations). Contractile responses of guinea pig tracheal preparations to carbachol and leukotriene C4, and relaxant responses to substance P and prostaglandin E2 were not affected by RCM-101. In rat aortic preparations, precontracted with phenylephrine, endothelium-dependent relaxant responses to acetylcholine and endothelium-independent relaxant responses to sodium nitroprusside were not affected by RCM-101. However, RCM-101 inhibited relaxations to l-arginine in endothelium-denuded rat aortic preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did not affect leukotriene B4 formation in isolated porcine neutrophils, induced by the calcium ionophore A23187; however, it inhibited prostaglandin E2 and NO production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7 cells).The findings indicate that RCM-101 may have multiple inhibitory actions on the release and/or synthesis of inflammatory mediators involved in allergic rhinitis. PMID:17549238

  3. Do early childhood immunizations influence the development of atopy and do they cause allergic reactions?

    PubMed

    Grüber, C; Nilsson, L; Björkstén, B

    2001-12-01

    Concerns about allergic side-effects of vaccines and about a possible promotion of allergic diseases contribute to incomplete vaccination rates in childhood. This article reviews the current understanding of these issues. There is evidence that pertussis and diphtheria/tetanus antigens elicit immunoglobulin E (IgE) antibody formation as part of the immune response. In murine models, pertussis toxin is an effective adjuvant for IgE formation against simultaneously administered antigens. In children, however, sensitization to unrelated antigens or development of allergic diseases do not seem to be augmented. In contrast, bacille Calmette-Guérin (BCG) and measles vaccination have been proposed as suppressors of allergy because of their T helper 1 (Th1)-fostering properties. In the murine system, BCG inhibits allergic sensitization and airway hyper-reactivity. Some epidemiological studies in humans suggest an inhibitory effect of tuberculosis on allergy. BCG vaccination in children, however, has no or merely a marginal suppressive effect on atopy. Other vaccine components such as egg proteins, gelatin, and antibiotics are a potential hazard to children with severe clinical reactions to these allergens. These rare children should be vaccinated under special precautions. In conclusion, vaccination programs do not explain the increasing prevalence of allergic diseases, but individual children may uncommonly develop an allergic reaction to a vaccine. The risks of not vaccinating children, however, far outweigh the risk for allergy. Therefore, childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed for allergy.

  4. Increased CCL24/Eotaxin-2 with Postnatal Ozone Exposure in Allergen-Sensitized Infant Monkeys Is Not Associated with Recruitment of Eosinophils to Airway Mucosa

    PubMed Central

    Chou, Debbie L.; Gerriets, Joan E.; Schelegle, Edward S.; Hyde, Dallas M.; Miller, Lisa A.

    2011-01-01

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. PMID:21945493

  5. United airway disease: current perspectives

    PubMed Central

    Giavina-Bianchi, Pedro; Aun, Marcelo Vivolo; Takejima, Priscila; Kalil, Jorge; Agondi, Rosana Câmara

    2016-01-01

    Upper and lower airways are considered a unified morphological and functional unit, and the connection existing between them has been observed for many years, both in health and in disease. There is strong epidemiologic, pathophysiologic, and clinical evidence supporting an integrated view of rhinitis and asthma: united airway disease in the present review. The term “united airway disease” is opportune, because rhinitis and asthma are chronic inflammatory diseases of the upper and lower airways, which can be induced by allergic or nonallergic reproducible mechanisms, and present several phenotypes. Management of rhinitis and asthma must be jointly carried out, leading to better control of both diseases, and the lessons of the Allergic Rhinitis and Its Impact on Asthma initiative cannot be forgotten. PMID:27257389

  6. Bee venom phospholipase A2 suppresses allergic airway inflammation in an ovalbumin-induced asthma model through the induction of regulatory T cells.

    PubMed

    Park, Soojin; Baek, Hyunjung; Jung, Kyung-Hwa; Lee, Gihyun; Lee, Hyeonhoon; Kang, Geun-Hyung; Lee, Gyeseok; Bae, Hyunsu

    2015-12-01

    Bee venom (BV) is one of the alternative medicines that have been widely used in the treatment of chronic inflammatory diseases. We previously demonstrated that BV induces immune tolerance by increasing the population of regulatory T cells (Tregs) in immune disorders. However, the major component and how it regulates the immune response have not been elucidated. We investigated whether bee venom phospholipase A2 (bvPLA2) exerts protective effects that are mediated via Tregs in OVA-induced asthma model. bvPLA2 was administered by intraperitoneal injection into control and OVA-challenged mice. The Treg population, total and differential bronchoalveolar lavage fluid (BALF) cell count, Th2 cytokines, and lung histological features were assessed. Treg depletion was used to determine the involvement of Treg migration and the reduction of asthmatic symptoms. The CD206-dependence of bvPLA2-treated suppression of airway inflammation was evaluated in OVA-challenged CD206(-/-) mice. The bvPLA2 treatment induced the Tregs and reduced the infiltration of inflammatory cells into the lung in the OVA-challenged mice. Th2 cytokines in the bronchoalveolar lavage fluid (BALF) were reduced in bvPLA2-treated mice. Although bvPLA2 suppressed the number of inflammatory cells after OVA challenge, these effects were not observed in Treg-depleted mice. In addition, we investigated the involvement of CD206 in bvPLA2-mediated immune tolerance in OVA-induced asthma model. We observed a significant reduction in the levels of Th2 cytokines and inflammatory cells in the BALF of bvPLA2-treated OVA-induced mice but not in bvPLA2-treated OVA-induced CD206(-/-) mice. These results demonstrated that bvPLA2 can mitigate airway inflammation by the induction of Tregs in an OVA-induced asthma model. PMID:26734460

  7. Tissue sensitivity of the rat upper and lower extrapulmonary airways to the inhaled electrophilic air pollutants diacetyl and acrolein.

    PubMed

    Cichocki, Joseph A; Smith, Gregory J; Morris, John B

    2014-11-01

    The target site for inhaled vapor-induced injury often differs in mouth-breathing humans compared with nose-breathing rats, thus complicating the use of rat inhalation toxicity data for assessment of human risk. We sought to examine sensitivity of respiratory/transitional nasal (RTM) and tracheobronchial (TBM) mucosa to two electrophilic irritant vapors: diacetyl and acrolein. Computational fluid dynamic physiologically based pharmacokinetic modeling was coupled with biomarker assessment to establish delivered dose-response relationships in RTM and TBM in male F344 rats following 6 h exposure to diacetyl or acrolein. Biomarkers included glutathione status, proinflammatory and antioxidant gene mRNA levels, and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Modeling revealed that 0.0094-0.1653 μg acrolein/min-cm(2) and 3.9-21.6 μg diacetyl/min-cm(2) were deposited into RTM/TBM. Results indicate RTM and TBM were generally of similar sensitivity to diacetyl and acrolein. For instance, both tissues displayed induction of antioxidant and proinflammatory genes, and nuclear accumulation of Nrf2 after electrophile exposure. Hierarchical cellular response patterns were similar in RTM and TBM but differed between vapors. Specifically, diacetyl exposure induced proinflammatory and antioxidant genes concomitantly at low exposure levels, whereas acrolein induced antioxidant genes at much lower exposure levels than that required to induce proinflammatory genes. Generally, diacetyl was less potent than acrolein, as measured by maximal induction of transcripts. In conclusion, the upper and lower extrapulmonary airways are of similar sensitivity to inhaled electrophilic vapors. Dosimetrically based extrapolation of nasal responses in nose-breathing rodents may provide an approach to predict risk to the lower airways of humans during mouth-breathing.

  8. Extravascular fibrin, plasminogen activator, plasminogen activator inhibitors, and airway hyperresponsiveness

    PubMed Central

    Wagers, Scott S.; Norton, Ryan J.; Rinaldi, Lisa M.; Bates, Jason H.T.; Sobel, Burton E.; Irvin, Charles G.

    2004-01-01

    Mechanisms underlying airway hyperresponsiveness are not yet fully elucidated. One of the manifestations of airway inflammation is leakage of diverse plasma proteins into the airway lumen. They include fibrinogen and thrombin. Thrombin cleaves fibrinogen to form fibrin, a major component of thrombi. Fibrin inactivates surfactant. Surfactant on the airway surface maintains airway patency by lowering surface tension. In this study, immunohistochemically detected fibrin was seen along the luminal surface of distal airways in a patient who died of status asthmaticus and in mice with induced allergic airway inflammation. In addition, we observed altered airway fibrinolytic system protein balance consistent with promotion of fibrin deposition in mice with allergic airway inflammation. The airways of mice were exposed to aerosolized fibrinogen, thrombin, or to fibrinogen followed by thrombin. Only fibrinogen followed by thrombin resulted in airway hyperresponsiveness compared with controls. An aerosolized fibrinolytic agent, tissue-type plasminogen activator, significantly diminished airway hyperresponsiveness in mice with allergic airway inflammation. These results are consistent with the hypothesis that leakage of fibrinogen and thrombin and their accumulation on the airway surface can contribute to the pathogenesis of airway hyperresponsiveness. PMID:15232617

  9. Dimethyl sulfoxide in a 10% concentration has no effect on oxidation stress induced by ovalbumin-sensitization in a guinea-pig model of allergic asthma.

    PubMed

    Mikolka, P; Mokra, D; Drgova, A; Petras, M; Mokry, J

    2012-04-01

    In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma. PMID:22653905

  10. Prevalence of allergic sensitization in the U.S.: Results from the National Health and Nutrition Examination Survey (NHANES) 2005–2006

    PubMed Central

    Salo, Päivi M.; Arbes, Samuel J.; Jaramillo, Renee; Calatroni, Agustin; Weir, Charles H.; Sever, Michelle L.; Hoppin, Jane A.; Rose, Kathryn M.; Liu, Andrew H.; Gergen, Peter J.; Mitchell, Herman E.; Zeldin, Darryl C.

    2014-01-01

    Background Allergic sensitization is an important risk factor for the development of atopic disease. The National Health and Nutrition Examination Survey (NHANES) 2005–2006 provides the most comprehensive information on IgE-mediated sensitization in the general US population. Objective We investigated clustering, sociodemographic and regional patterns of allergic sensitization and examined risk factors associated with IgE-mediated sensitization. Methods Data for this cross-sectional analysis were obtained from NHANES 2005–2006. Participants aged ≥1 year (N=9440) were tested for sIgEs to inhalant and food allergens; participants ≥6 years were tested for 19 sIgEs, and children aged 1–5 years for 9 sIgEs. Serum samples were analyzed using the ImmunoCAP System. Information on demographics and participant characteristics was collected by questionnaire. Results Of the study population aged 6 and older, 44.6% had detectable sIgEs, while 36.2% of children aged 1–5 years were sensitized to ≥1 allergen. Allergen-specific IgEs clustered into 7 groups that might have largely reflected biological cross-reactivity. Although sensitization to individual allergens and allergen types showed regional variation, the overall prevalence of sensitization did not differ across census regions, except in early childhood. In multivariate modeling, young age, male gender, non-Hispanic black race/ethnicity, geographic location (census region), and reported pet avoidance measures were most consistently associated with IgE-mediated sensitization. Conclusions The overall prevalence of allergic sensitization does not vary across US census regions, except in early life, although allergen-specific sensitization differs by sociodemographic and regional factors. Biological cross-reactivity may be an important, but not a sole, contributor to the clustering of allergen-specific IgEs. Clinical implications IgE-mediated sensitization shows clustering patterns and differs by sociodemographic

  11. Latex-allergic patients sensitized to the major allergen hevein and hevein-like domains of class I chitinases show no increased frequency of latex-associated plant food allergy

    PubMed Central

    Radauer, Christian; Adhami, Farzaneh; Fürtler, Irene; Wagner, Stefan; Allwardt, Dorothee; Scala, Enrico; Ebner, Christof; Hafner, Christine; Hemmer, Wolfgang; Mari, Adriano; Breiteneder, Heimo

    2011-01-01

    Allergies to certain fruits such as banana, avocado, chestnut and kiwi are described in 30–70% of latex-allergic patients. This association is attributed to the cross-reactivity between the major latex allergen hevein and hevein-like domains (HLDs) from fruit class I chitinases. We aimed to assess the extent of cross-reactivity between hevein and HLDs using sera from latex-allergic patients with and without plant food allergy. Hevein and HLDs of latex, banana, and avocado chitinases were expressed in Escherichia coli as fusion proteins with the maltose-binding protein and purified by affinity chromatography. IgE binding to these proteins was studied in sera from 59 latex-allergic patients and 20 banana-allergic patients without latex allergy by ELISA and ELISA inhibition. Additionally, 16,408 allergic patients’ sera were tested for IgE binding to hevein, latex chitinase, and wheat germ agglutinin using an allergen microarray. Hevein-specific IgE was detected in 34/59 (58%) latex-allergic patients’ sera. HLDs of latex, banana, and avocado chitinases were recognized by 21 (36%), 20 (34%), and 9 (15%) sera, respectively. In contrast, only one of 20 banana-allergic patients without latex allergy was sensitized to chitinase HLDs. In most tested latex-allergic patients’ sera, IgE binding to hevein was only partially reduced by preincubation with HLDs. Among hevein-sensitized, latex-allergic patients, the percentage of plant food allergy (15/34 = 44%) was equal to latex-allergic patients without hevein sensitization (11/25 = 44%). In the general allergic population, 230 of 16,408 sera (1.4%) reacted to hevein and/or a hevein-like allergen. Of these, 128 sera showed an isolated sensitization to hevein, whereas only 17 bound to latex chitinase or wheat germ agglutinin without hevein sensitization. In conclusion, the IgE response to HLDs is elicited by hevein as sensitizing allergen in most cases. Despite considerable cross-reactivity between these allergens, no

  12. Associations of allergic sensitization and clinical phenotypes with innate immune response genes polymorphisms are modified by house dust mite allergen exposure

    PubMed Central

    Kurowski, Marcin; Majkowska-Wojciechowska, Barbara; Wardzyńska, Aleksandra

    2011-01-01

    Introduction Polymorphisms within innate immunity genes are associated with allergic phenotypes but results are variable. These associations were not analyzed with respect to allergen exposure. We investigated associations of TLR and CD14 polymorphisms with allergy phenotypes in the context of house dust mite (HDM) exposure. Material and methods Children, aged 12-16 years (n=326), were recruited from downtown and rural locations and assessed by allergist. Skin prick tests, total and HDM-specific sIgE measurements were done. HDM allergen concentrations in dust were measured. Genetic polymorphisms were identified using restriction fragment length polymorphism (RFLP). Results Allergic rhinitis, asthma and atopy were more prevalent in urban area. Although HDM allergen concentrations were higher in rural households, sIgE were present more frequently in urban children. In the whole population no association was found between HDM exposure and sensitization. In children with CD14/−159CC, CD14/−159TT and TLR9/2848GA genotypes increased exposure to HDM was associated with reduced incidence of allergic rhinitis. Significant associations of increased HDM exposure with reduced incidence of atopy were found for the whole population and subjects with CD14/−159CC, CD14/−1359GT, TLR4/896AA and TLR9/2848GA genotypes. Among children with CD14/−159CC and CD14/−1359GG significant positive correlation between HDM allergen concentrations in household and sensitization to HDM was observed. In contrast, protective effect of high HDM allergen exposure against specific sensitization was seen in subjects with TLR4/896 AG. Conclusions Development of specific sensitization and allergy may be associated with innate immune response genes polymorphisms and is modified by allergen exposure. PMID:22328887

  13. What could be the role of molecular-based allergy diagnostics in detecting the risk of developing allergic sensitization to furry animals?

    PubMed

    Liccardi, Gennaro; Bilò, M B; Manzi, F; Piccolo, A; Di Maro, E; Salzillo, A

    2015-09-01

    Although this highly refined diagnostic approach has been used in several fields of allergy diagnosis, we noticed the scarcity of data on the role of CDR in detecting current sensitization to the allergens of common pets (cat / dog) and, especially, its potential usefulness in predicting the risk of sensitization to other furry animals. Reported data suggest that cross-reacting mechanisms might play an important role in a significant proportion of allergic sensitizations to furry animals (common pets and unusual / exotic mammals) especially in the absence of any possible direct / indirect contact. In this context an evaluation of specific IgE by using the micro-array technique ImmunoCAP ISAC (Thermofisher Scientific - Immuno-Diagnostics, Sweden) for lipocalins (Can f 1, Can f 2, Equ c 1, Fel d 4, Mus m 1) and albumins (Bos d 6, Can f 3, Equ c 3, Fel d 2) might be very useful to evaluate the possibility of cross-reactions between the allergens of different animals. In fact, allergic sensitization without animal exposure is a relevant risk for patients, because they are not aware about the possibility that even severe respiratory symptoms may develop after an occasional animal contact. This aspect should be taken into account by susceptible individuals before acquiring new pets, after removal of common pets or beginning a contact for working / leisure activity with a common as well as uncommon animal.

  14. Interference of a short-term exposure to nitrogen dioxide with allergic airways responses to allergenic challenges in BALB/c mice.

    PubMed Central

    Proust, Barbara; Lacroix, Ghislaine; Robidel, Franck; Marliere, Maryse; Lecomte, Anthony; Vargaftig, B Boris

    2002-01-01

    Nitrogen dioxide (NO(2)) is a common indoor and outdoor air pollutant whose role in the induction of asthma is unclear. We investigated the effects of NO(2) on the development of asthma-like responses to allergenic challenge in BALB/c mice. Ovalbumin (OVA)-immunized mice were intranasally challenged with OVA or saline solution just before starting a 3 h exposure to 5 or 20 ppm NO(2) or air. Twenty parts per million of NO(2) induced a significant increase of bronchopulmonary hyperreactivity in OVA-challenged mice and of permeability according to the fibronectin content of the bronchoalveolar lavage fluid (BALF) 24 h after exposure, as compared with air or 5 ppm NO(2). Eosinophilia (cell counts in the BALF and eosinophil peroxidase of lung tissue) was detected at 24 and 72 h with similar levels for air and 20 ppm NO(2), whereas a marked reduction was unexpectedly observed for 5 ppm NO(2). At 24 h, interleukin-5 in the BALF was markedly reduced at 5 ppm compared with 20 ppm NO(2) and was also more intense for 20 ppm NO(2) than for the air group. In contrast to specific IgG1 titers, anti-OVA IgE titers and interleukin-4 in the BALF were not affected by NO(2) exposure. Irrespective of the concentration of NO(2), OVA-challenged mice did not develop late mucosal metaplasia compared with those exposed to OVA-air. These results indicate that a short exposure to NO(2) can exacerbate or inhibit some features of the development of allergic disease in mice and may depend on the concentration of pollutant. PMID:12396477

  15. Morphometric changes during the early airway response to allergen challenge in the rat.

    PubMed

    Du, T; Xu, L J; Lei, M; Wang, N S; Eidelman, D H; Ghezzo, H; Martin, J G

    1992-10-01

    The purpose of this study was to determine the relative contributions of airway wall edema and smooth muscle contraction to the early response (ER) of allergic bronchoconstriction. Brown Norway rats, 6 to 7 wk old, were sensitized with ovalbumin (OA). Anesthetized rats were challenged with either OA or saline 2 wk later. Pulmonary resistance (RL) was measured every minute until either it increased to 150% of the baseline, defined as a significant ER, or until 15 min elapsed. Eight OA-challenged test rats with a significant ER and eight saline-challenged control rats were used for morphometric studies. The lungs were quick-frozen with liquid nitrogen, processed with freeze substitution, and sagittal sections (5 microns) were stained with hematoxylin and eosin. The airway lumen subtended by the epithelial basement membrane (LuB) and cross sectional airway wall area (AW) of all airways were measured by camera lucida and digitization. The LuB and AW of each airway was standardized for size by dividing by the ideal airway lumen (LuBideal), which was calculated from the length of basement membrane, assuming a perfect circle in the unconstricted state. The cumulative frequency distribution of the LuB/LuBideal for the airways from test rats was shifted to the left compared with the control rats (p less than 0.01), indicating airway narrowing after challenge. Airway narrowing increased as a function of airway size. Cumulative frequency distributions of AW/LuBideal showed that there was a significant increase in the wall thickness of only the small airways of test animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1416393

  16. Hyaluronan fragments as mediators of inflammation in allergic pulmonary disease

    PubMed Central

    Ghosh, Sumit; Hoselton, Scott A.; Dorsam, Glenn P.; Schuh, Jane M.

    2015-01-01

    Asthma is frequently caused and/or exacerbated by sensitization to allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen, leading to a disease course that is often very difficult to treat with standard asthma therapies. As a result of interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to allergens may experience a greater degree of tissue injury followed by airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. In addition, turnover of extracellular matrix (ECM) components is a hallmark of tissue injury and repair. This review focuses on the role of the glycosaminoglycan hyaluronan (HA), a component of the ECM, in pulmonary injury and repair with an emphasis on allergic asthma. Both the synthesis and degradation of the ECM are critical contributors to tissue repair and remodeling. Fragmented HA accumulates during tissue injury and functions in ways distinct from the larger native polymer. There is gathering evidence that HA degradation products are active participants in stimulating the expression of inflammatory genes in a variety of immune cells at the injury site. In this review, we will consider recent advances in the understanding of the mechanisms that are associated with HA accumulation and inflammatory cell recruitment in the asthmatic lung. PMID:25582403

  17. ALLERGIC DISEASES AND ASTHMA IN ADOLESCENTS.

    PubMed

    Adamia, N; Jorjoliani, L; Khachapuridze, D; Katamadze, N; Chkuaseli, N

    2015-06-01

    The goal of our research was to find out, whether asthma phenotyping, based on presence of accompanying allergic diseases is significant for asthma classification or not. Research was conducted on the basis of questioning of random and representative cohorts of Tbilisi children's population, by cross-section method of epidemiological research. Special extended screening questionnaire was developed for epidemiological study of allergic diseases. Diagnostic criterion for allergy was analyzed and representative cohort was selected. Research was conducted in 2010-2014 period. Studied population included 1450 children from 2 to 17 years age representing Tbilisi general population (of them, 850 girls and 600 boys). As a result of research the following findings were made: asthma was confirmed where at least two of the listed was present: diagnosis of asthma made by doctor, asthma symptoms and consumption of drugs against asthma. Allergic rhinitis was confirmed, where more than one of the listed symptoms was present and children should not have caught cold, rhinorrhea, nasal obstruction or snore, combined or IgE with some inhalation allergen. Atopic dermatitis was confirmed if the subject had atopic dermatitis at a time of interview or clinical study. Markers of asthma severity were based on number of asthma episodes and number of symptoms, or regular consumption of corticosteroids, number of missed days at school and answer of subjects to the question: for the past year what was the degree of discomfort attributable to asthma ("very high" - "absolutely not"). Allergic sensitization was assessed based on the skin prick-test and test of specific immunoglobulin E in serum and was deemed positive where the average diameter of blebs in skin prick tests was 3 mm larger than negative control and IgE-0,35kU/l. Lung function was assessed by means of respirometers, by evaluating maximal forced expiration data and flow-volume curves. Allergic rhinitis was regarded as the most

  18. C-027 inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways.

    PubMed

    Cooper, Philip R; Zhang, Jie; Damera, Gautam; Hoshi, Toshinori; Zopf, David A; Panettieri, Reynold A

    2011-01-01

    Atopic asthma is poorly controlled by current therapies. Newer therapies and novel antihistamines are, therefore, required to treat patients whose atopic asthma is not controlled. For the first time, C-027 is shown to antagonize histamine, IgE-mediated and serotonin-induced contraction in human airways and vessels. Human precision-cut lung slices (PCLS, 250 μm thick), containing an airway or blood vessel, were pretreated with either C-027 (2 hours) or with vehicle alone and were contracted with histamine or serotonin. Known antihistamine was used as a comparator in antihistamine studies. Also, human airways were contracted via IgE passive sensitization in the presence or absence of C-027 or fexofenadine. Affinity of C-027 toward human G-protein coupled receptors was also determined, as well as the drug's biodistribution in murine model. C-027 was shown to have the highest affinity toward human histamine and serotonin receptors. Subsequently, C-027 was shown to antagonize histamine- and serotonin-induced airway and vascular smooth muscle contraction, respectively, and histamine-released bronchocontraction mediated by IgE passive sensitization in human small airways. C-027 also inhibited histamine-mediated single-cell calcium ion release. Low levels of C-027 were found in murine brain tissue. Collectively, these data suggest that C-027 markedly inhibits IgE-induced bronchoconstriction and antagonizes histamine and serotonin-contraction with little biodistribution in the brain. The compound may offer a future therapy for allergen-induced airway hyperresponsiveness in patients with asthma.

  19. Effect of ozone exposure on antigen-induced airway hyperresponsiveness in guinea pigs

    SciTech Connect

    Vargas, M.H.; Segura, P.; Campos, M.G.; Hong, E.; Montano, L.M.

    1994-12-31

    Airway hyperresponsiveness can be induced by several stimuli including antigen and ozone, both of which may be present in the air of polluted cities. Though the effect of ozone on the bronchoconstrictor response to antigen has been well described, the combined effect of these stimuli on airway hyperresponsiveness has not yet been studied. Sensitized guinea pigs with or without ozone exposure for 1 h at 3 ppm, 18 h prior to study, were challenged with a dose-response curve to histamine (0.01-1.8 {mu}g/kg, iv), and then by a second histamine dose-response curve 1 h later. Airway responses were measured as the increase in pulmonary insufflation pressure. In sensitized guinea pigs, the histamine ED50 significantly decreased after antigen challenge, demonstrating the development of airway hyperresponsiveness. Sensitized guinea pigs exposed to ozone showed airway hyperresponsiveness to histamine when compared with nonexposed animals, and such hyperresponsiveness was further enhanced after antigen challenge. We conclude that in this guinea pig model of acute allergic bronchoconstriction both antigen challenge and ozone induce airway hyperresponsiveness, while ozone exposure does not modify the development of antigen-induced hyperresponsiveness. 25 refs., 1 fig., 1 tab.

  20. Allergic Reactions

    MedlinePlus

    ... immune system identifies pollen as an invader or allergen. Your immune system overreacts by producing antibodies called ... IgE has specific "radar" for each type of allergen. That's why some people are only allergic to ...

  1. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported.

  2. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. PMID:27090934

  3. Allergic Fungal Rhinosinusitis.

    PubMed

    Hoyt, Alice E W; Borish, Larry; Gurrola, José; Payne, Spencer

    2016-01-01

    This article reviews the history of allergic fungal rhinosinusitis and the clinical, pathologic, and radiographic criteria necessary to establish its diagnosis and differentiate this disease from other types of chronic rhinosinusitis. Allergic fungal rhinosinusitis is a noninvasive fungal form of sinus inflammation characterized by an often times unilateral, expansile process in which the typical allergic "peanut-butter-like" mucin contributes to the formation of nasal polyps, hyposmia/anosmia, and structural changes of the face. IgE sensitization to fungi is a necessary, but not sufficient, pathophysiologic component of the disease process that is also defined by microscopic visualization of mucin-containing fungus and characteristic radiological imaging. This article expounds on these details and others including the key clinical and scientific distinctions of this diagnosis, the pathophysiologic mechanisms beyond IgE-mediated hypersensitivity that must be at play, and areas of current and future research. PMID:27393774

  4. [Allergic risk in anaesthesia].

    PubMed

    Mertes, Paul Michel; De Blay, Frédéric; Dong, Siwei

    2013-03-01

    Anaphylactic reactions may be either of immune(allergy, usually IgE-mediated, sometimes IgG-mediated) or non-immune origin. The incidence of anaphylactic reactions during anaesthesia varies between countries ranging from 1/1250 to 1/13,000 per procedure. In France, the estimated incidence of allergic reactions is 100.6 [76.2-125.3]/million procedures with a high female predominance (male: 55.4 [42.0-69.0], female: 154.9 [117.2-193.1]). This predominance is not observed in children. In adults, the most frequently incriminated substances are neuromuscular blocking agents, followed by latex and antibiotics. The estimated incidence of allergic reactions to neuromuscular blocking agents is 184.0 [139.3-229.7]/million procedure. In most cases there is a close reaction between clinical symptoms and drug administration. When the reaction is delayed, occurring during the surgical procedure, a reaction involving latex, a vital dye, an antiseptic or a volume expanding fluid should be suspected. Reaction severity may vary. The most frequently reported initial symptoms are pulselessness, erythema, increased airway pressure, desaturation or decreased end-tidal CO2. Clinical symptoms may occur as an isolated condition, making proper diagnosis difficult. In some cases a cardiovascular arrest can be observed. Reaction mechanism identification relies on mediators (tryptase, histamine) measurement at the time of the reaction. In case of allergic reaction, the responsible drug can be identified by the detection of specific IgE using immunoassays or by skin tests performed 6 weeks after the reaction. Predictive allergy investigation to latex or anaesthetics in the absence of history of reaction should be restricted to at-risk patients. Premedication cannot prevent the onset of an allergic reaction. Providing a latex-free environment can be used for primary or secondary prevention. Treatment is based on allergen administration interruption, epinephrine administration in a titrated

  5. Anti-allergic effect of intranasal administration of type-A procyanidin polyphenols based standardized extract of cinnamon bark in ovalbumin sensitized BALB/c mice.

    PubMed

    Aswar, Urmila M; Kandhare, Amit D; Mohan, Vishwaraman; Thakurdesai, Prasad A

    2015-03-01

    The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR.

  6. Anti-allergic effect of intranasal administration of type-A procyanidin polyphenols based standardized extract of cinnamon bark in ovalbumin sensitized BALB/c mice.

    PubMed

    Aswar, Urmila M; Kandhare, Amit D; Mohan, Vishwaraman; Thakurdesai, Prasad A

    2015-03-01

    The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR. PMID:25504814

  7. Upper airway CO2 receptors in tegu lizards: localization and ventilatory sensitivity.

    PubMed

    Coates, E L; Ballam, G O

    1987-01-01

    1. Tidal volume, end-tidal CO2, and ventilatory frequency in Tupinambis nigropunctatus were measured in response to CO2 (1-4%) delivered to either the mouth or nares. Additionally, the sensitivity of the ventilatory response to nasal CO2 was evaluated at CO2 concentrations less than 1%. The ventilatory parameters were also measured in response to CO2 (1-4%) delivered to the nares after the olfactory peduncle was transected. 2. It was found that (0.4-4%) nasal CO2 depressed ventilatory frequency by 9% to 83% respectively, while tidal volume was not significantly altered. CO2 (1-4%) delivered to the mouth produced no apparent changes in any of the ventilatory parameters. Following transection of the olfactory peduncle, nasal CO2 was ineffective in producing any change in ventilatory frequency or depth. 3. These findings indicate that CO2-sensitive receptors are located in either the nasal or vomeronasal membranes of tegu lizards and that the olfactory peduncle must be intact for these receptors to affect ventilatory changes in response to elevated CO2 concentrations. The receptors are capable of mediating a ventilatory response to CO2 concentrations lower than those found in either expired air or in confined spaces such as occupied burrows. 4. The discrepancies in the ventilatory responses of lizards and snakes to inspired CO2 reported in past experiments may be partially explained by the presence of nasal or vomeronasal CO2-sensitive receptors.

  8. Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

    PubMed Central

    Kozakova, Hana; Schwarzer, Martin; Tuckova, Ludmila; Srutkova, Dagmar; Czarnowska, Elzbieta; Rosiak, Ilona; Hudcovic, Tomas; Schabussova, Irma; Hermanova, Petra; Zakostelska, Zuzana; Aleksandrzak-Piekarczyk, Tamara; Koryszewska-Baginska, Anna; Tlaskalova-Hogenova, Helena; Cukrowska, Bozena

    2016-01-01

    Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans. PMID:25942514

  9. Prenatal and Postnatal Polycyclic Aromatic Hydrocarbon Exposure, Airway Hyperreactivity, and Beta-2 Adrenergic Receptor Function in Sensitized Mouse Offspring

    PubMed Central

    Zhang, Hanjie; Maher, Christina; McDonald, Jacob D.; Zhang, Xiang; Ho, Shuk-Mei; Yan, Beizhan; Chillrud, Steven; Perera, Frederica; Factor, Phillip; Miller, Rachel L.

    2013-01-01

    Despite data associating exposure to traffic-related polycyclic aromatic hydrocarbons (PAH) in asthma, mechanistic support has been limited. We hypothesized that both prenatal and early postnatal exposure to PAH would increase airway hyperreactivity (AHR) and that the resulting AHR may be insensitive to treatment with a β2AR agonist drug, procaterol. Further, we hypothesized that these exposures would be associated with altered β2AR gene expression and DNA methylation in mouse lungs. Mice were exposed prenatally or postnatally to a nebulized PAH mixture versus negative control aerosol 5 days a week. Double knockout β2AR mice were exposed postnatally only. Prenatal exposure to PAH was associated with reduced β2AR gene expression among nonsensitized mice offspring, but not increases in DNA methylation or AHR. Postnatal exposure to PAH was borderline associated with increased AHR among sensitized wildtype, but not knockout mice. In the first study that delivers PAH aerosols to mice in a relatively physiological manner, small effects on AHR and β2AR gene expression, but not β2AR agonist drug activity, were observed. If confirmed, the results may suggest that exposure to PAH, common ambient urban pollutants, affects β2AR function, although the impact on the efficacy of β2AR agonist drugs used in treating asthma remains uncertain. PMID:24454363

  10. The compatible solute ectoine reduces the exacerbating effect of environmental model particles on the immune response of the airways.

    PubMed

    Unfried, Klaus; Kroker, Matthias; Autengruber, Andrea; Gotić, Marijan; Sydlik, Ulrich

    2014-01-01

    Exposure of humans to particulate air pollution has been correlated with the incidence and aggravation of allergic airway diseases. In predisposed individuals, inhalation of environmental particles can lead to an exacerbation of immune responses. Previous studies demonstrated a beneficial effect of the compatible solute ectoine on lung inflammation in rats exposed to carbon nanoparticles (CNP) as a model of environmental particle exposure. In the current study we investigated the effect of such a treatment on airway inflammation in a mouse allergy model. Ectoine in nonsensitized animals significantly reduced the neutrophilic lung inflammation after CNP exposure. This effect was accompanied by a reduction of inflammatory factors in the bronchoalveolar lavage. Reduced IL-6 levels in the serum also indicate the effects of ectoine on systemic inflammation. In sensitized animals, an aggravation of the immune response was observed when animals were exposed to CNP prior to antigen provocation. The coadministration of ectoine together with the particles significantly reduced this exacerbation. The data indicate the role of neutrophilic lung inflammation in the exacerbation of allergic airway responses. Moreover, the data suggest to use ectoine as a preventive treatment to avoid the exacerbation of allergic airway responses induced by environmental air pollution.

  11. Differential sensitivity of normal and cystic fibrosis airway epithelial cells to epinephrine.

    PubMed

    Goncz, K K; Feeney, L; Gruenert, D C

    1999-09-01

    1. Exposure to epinephrine has been shown to have a range of effects on cells and tissues. A recent study suggested that the proliferative ability of CF epithelial cells, exposed to high concentrations of epinephrine (200 - 300 microM), was reduced when compared to that of normal cells. This approach could potentially provide a means to effectively separate cells with functional cyclic AMP-dependent Cl-ion transport from those defective in this pathway. 2. The sensitivity to killing by epinephrine is reported here for four different CF cell lines, three normal cell lines, and two CF epithelial cell lines complemented with wild-type (wt) CF transmembrane conductance regulator (CFTR) cDNA. 3. While each cell line exhibited varying sensitivity to 200 microM epinephrine, no predictable pattern was observed between the expression of wt-CFTR and cell survival following epinephrine exposure. Overall, normal cell lines did exhibit a greater resistance to epinephrine-induced cell death although, the most resistant cell line was derived from CF tracheal epithelium (SigmaCFTE29o-). 4. The expression of exogenous wt-CFTR increased the survival of one cell line (CFDEo-) when compared to the parent line, but in another complemented line, survival was reduced. 5. These findings suggest that while epinephrine induces cell killing, it is not consistently effective for preferential selection of normal over CF cells. Although CFTR may play a role in the mechanism(s) of epinephrine killing, other factors such as cell density, proliferative ability, cell type origin and phenotype are involved.

  12. Allergic Rhinitis.

    PubMed

    Kakli, Hasan A; Riley, Timothy D

    2016-09-01

    Among the atopic disorders, allergic rhinitis is the most prevalent. Patients who suffer from allergic rhinitis sustain significant morbidity and loss of productivity. Cardinal symptoms include nasal congestion, rhinorrhea, sneezing, and nasal itching, although multiple related symptoms may occur. Causes should be ruled out with a thorough history and physical examination, with particular attention to red flag or atypical symptoms. Skin testing or serum sampling can confirm diagnosis and also guide therapy. Therapy is multimodal, tailored to a particular patient's symptom burden and quality of life. PMID:27545735

  13. Prominent features of allergic angioedema on oral mucosa.

    PubMed

    Duvancić, Tomislav; Lugović-Mihić, Liborija; Brekalo, Ante; Situm, Mirna; Sinković, Ana

    2011-12-01

    Angioedema indicates acute subcutaneous edema that characterizes improperly restricted cutaneous or mucous membrane swelling, which can occur only once or be relapsing. Edema usually occurs in the periorbital area, lips, tongue, extremities and intestinal wall. It has turned out that angioedema is usually caused by the use of angiotensin-converting enzyme inhibitors (ACE) or allergies to certain allergens (allergic or IgE-mediated angioedema), followed by C1 inhibitor deficiency (hereditary and acquired angioedema), or the cause is unknown (idiopathic angioedema). It has been shown that patients with angioedema often have urticaria, which is noted in approximately 50% of cases. Usually there is a type I allergic reaction to some food allergens or drugs or insect stings. The most common causes of allergic angioedema are bee and wasp stings, reactions to medications or injections for sensitivity testing, and certain foods (especially eggs, shellfish and nuts). In diagnostic terms, it is important to determine the potential allergen, which is commonly performed with cutaneous tests, such as prick test, etc. The main risk of angioedema is swelling of the tongue, larynx and trachea, which can lead to airway obstruction and death, therefore tracheotomy is indicated in such cases. The initial treatment of patients with most forms of angioedema included administration of antihistamines and glucocorticoids, while epinephrine is given if there is fear from laryngeal edema.

  14. [Clinical diagnosis and treatment of allergic pharyngitis].

    PubMed

    Liu, Jinfeng; Yan, Zhanfeng; Zhang, Mingxia

    2015-08-01

    Although the concept of united airway disease has been widely accepted, most scholars emphasize only the effect of rhino-sinusitis while ignoring the pharyngeal factors to the lower airway, especially to the allergic pharyngitis (AP), which still lacks enough awareness. First of all, absence of unified diagnostic standard leads to the lack of epidemiological data, which, results in doctors' personal experience but no guideline in treatments. In addition, it is still not clear that the role of AP in the allergic airway diseases and its relationship with asthma. However, the number of patients with AP has been increasing obviously in daily clinic practice. Combined with the previous observation, this paper does a systematic review about the clinical problems of AP, expecting to give a hand to the clinical diagnosis and treatment of AP. PMID:26685417

  15. Allergic and non-allergic rhinitis: relationship with nasal polyposis, asthma and family history.

    PubMed

    Gelardi, M; Iannuzzi, L; Tafuri, S; Passalacqua, G; Quaranta, N

    2014-02-01

    Rhinitis and rhinosinusitis (with/without polyposis), either allergic or non-allergic, represent a major medical problem. Their associated comorbidities and relationship with family history have so far been poorly investigated. We assessed these aspects in a large population of patients suffering from rhinosinusal diseases. Clinical history, nasal cytology, allergy testing and direct nasal examination were performed in all patients referred for rhinitis/rhinosinusitis. Fibre optic nasal endoscopy, CT scan and nasal challenge were used for diagnosis, when indicated. A total of 455 patients (60.7% male, age range 4-84 years) were studied; 108 (23.7%) had allergic rhinitis, 128 (28.1%) rhinosinusitis with polyposis, 107 (23.5%) non-allergic rhinitis (negative skin test); 112 patients had associated allergic and non-allergic rhinitis, the majority with eosinophilia. There was a significant association between non-allergic rhinitis and family history of nasal polyposis (OR = 4.45; 95%CI = 1.70-11.61; p = 0.0019), whereas this association was no longer present when allergic rhinitis was also included. Asthma was equally frequent in non-allergic and allergic rhinitis, but more frequent in patients with polyposis. Aspirin sensitivity was more frequent in nasal polyposis, independent of the allergic (p = 0.03) or non-allergic (p = 0.01) nature of rhinitis. Nasal polyposis is significantly associated with asthma and positive family history of asthma, partially independent of the allergic aetiology of rhinitis.

  16. Effects of Selective Inhibition of PDE4 by YM976 on Airway Reactivity and Cough in Ovalbumin-Sensitized Guinea Pigs.

    PubMed

    Mokrý, J; Urbanová, A; Medvedová, I; Kertys, M; Mikolka, P; Kosutová, P; Mokrá, D

    2016-01-01

    Phosphodiesterases (PDEs) are enzymes involved in the degradation of cAMP and cGMP. Selective PDE4 inhibitors (e.g., roflumilast) are effective in therapy of chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate the effects of a selective PDE4 inhibitor, YM976, on citric acid-induced cough, in vivo and in vitro airway smooth muscle reactivity to histamine, and on inflammatory mediators in ovalbumin-sensitized guinea pigs, with experimentally induced eosinophil inflammation. The YM976 was administered intraperitoneally at a dose of 1.0 mg/kg once daily for 7 days. Sensitization with ovalbumin led to a significant increase in the number of coughs, and in vivo and in vitro airway reactivity. Also, increased plasma levels of IL-4, IL-5, and PAF were observed, with a significant increase in the differential count of eosinophils in both blood and bronchoalveolar lavage fluid. The YM976 suppressed the number of coughs, the airway reactivity in tracheal tissue strips, and the IL-4 level. The findings indicate that PDE4 inhibition by YM976 exerts antitussive and anti-inflammatory effects in guinea pigs with ovalbumin-induced eosinophilic inflammation. PMID:27130219

  17. Allergic contact dermatitis.

    PubMed

    Becker, Detlef

    2013-07-01

    Allergic contact dermatitis is a frequent inflammatory skin disease. The suspected diagnosis is based on clinical symptoms, a plausible contact to allergens and a suitable history of dermatitis. Differential diagnoses should be considered only after careful exclusion of any causal contact sensitization. Hence, careful diagnosis by patch testing is of great importance. Modifications of the standardized test procedure are the strip patch test and the repeated open application test. The interpretation of the SLS (sodium lauryl sulfate) patch test as well as testing with the patients' own products and working materials are potential sources of error. Accurate patch test reading is affected in particular by the experience and individual factors of the examiner. Therefore, a high degree of standardization and continuous quality control is necessary and may be supported by use of an online patch test reading course made available by the German Contact Dermatitis Research Group. A critical relevance assessment of allergic patch test reactions helps to avoid relapses and the consideration of differential diagnoses. Any allergic test reaction should be documented in an allergy ID card including the INCI name, if appropriate. The diagnostics of allergic contact dermatitis is endangered by a seriously reduced financing of patch testing by the German statutory health insurances. Restrictive regulations by the German Drug Law block the approval of new contact allergens for routine patch testing. Beside the consistent avoidance of allergen contact, temporary use of systemic and topical corticosteroids is the therapy of first choice.

  18. Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa1

    PubMed Central

    Hara, Kenichiro; Iijima, Koji; Elias, Martha K.; Seno, Satoshi; Tojima, Ichiro; Kobayashi, Takao; Kephart, Gail M.; Kurabayashi, Masahiko; Kita, Hirohito

    2014-01-01

    While type 2 immune responses to environmental antigens are thought to play pivotal roles in asthma and allergic airway diseases, the immunological mechanisms that initiate the responses are largely unknown. Many allergens have biologic activities, including enzymatic activities and abilities to engage innate pattern-recognition receptors such as TLR4. Here we report that IL-33 and thymic stromal lymphopoietin (TSLP) were produced quickly in the lungs of naïve mice exposed to cysteine proteases, such as bromelain and papain, as a model for allergens. IL-33 and TSLP sensitized naïve animals to an innocuous airway antigen OVA, which resulted in production of type 2 cytokines and IgE antibody and eosinophilic airway inflammation when mice were challenged with the same antigen. Importantly, upon exposure to proteases, uric acid (UA) was rapidly released into the airway lumen, and removal of this endogenous UA by uricase prevented type 2 immune responses. UA promoted secretion of IL-33 by airway epithelial cells in vitro, and administration of UA into the airways of naïve animals induced extracellular release of IL-33, followed by both innate and adaptive type 2 immune responses in vivo. Finally, a potent UA synthesis inhibitor, febuxostat, mitigated asthma phenotypes that were caused by repeated exposure to natural airborne allergens. These findings provide mechanistic insights into the development of type 2 immunity to airborne allergens and recognize airway UA as a key player that regulates the process in respiratory mucosa. PMID:24663677

  19. Expression and function of a novel variant of estrogen receptor-α36 in murine airways.

    PubMed

    Jia, Shuping; Zhang, Xintian; He, David Z Z; Segal, Manav; Berro, Abdo; Gerson, Trevor; Wang, Zhaoyi; Casale, Thomas B

    2011-11-01

    Evidence suggests that estrogen signaling is involved in sex differences in the prevalence rates and control of asthma, but the expression patterns of estrogen receptor variants and estrogen function in the lung are not well established. We investigated the expression of major estrogen receptor variants occurring naturally and after the development of allergen-induced airway hyperreactivity in a murine model of allergic asthma, along with the role of estrogen signaling in small-airway ciliary motion and smooth muscle contraction. Female BALB/c mice were sensitized with ovalbumin, and estrogen receptor expression patterns were examined by immunofluorescence and Western blot analysis. Time-lapse video and photodiode-based displacement measurement systems were used to assess the effects of estrogen signaling on airway ciliary beat frequency and smooth muscle contraction. We found that a novel variant of estrogen receptor (ER)-α, ER-α36, is expressed in airway epithelial and smooth muscle cells. ER-α36 was predominately localized on the plasma membranes of airway cells. After sensitization to allergen, the expression levels of ER-α36 increased significantly (P < 0.01), whereas the expression of ER-β and ER-α66 did not significantly change. Estrogen treatment in vitro resulted in a rapid increase in airway cilia motion in a dose-dependent fashion, but did not exert any effect on airway smooth muscle contraction. We speculate that the up-regulation of estrogen receptor expression associated with allergen-induced airway hyperresponsiveness may constitute a protective mechanism to facilitate the clearance of mucus. The identification and localization of specific estrogen receptor subtypes in the lung could lead to newer therapeutic avenues aimed at addressing sex differences of asthma susceptibility. PMID:21642591

  20. Sensitization to Indigenous Pollen and Molds and Other Outdoor and Indoor Allergens in Allergic Patients From Saudi Arabia, United Arab Emirates, and Sudan

    PubMed Central

    2012-01-01

    Background Airborne allergens vary from one climatic region to another. Therefore, it is important to analyze the environment of the region to select the most prevalent allergens for the diagnosis and treatment of allergic patients. Objective To evaluate the prevalence of positive skin tests to pollen and fungal allergens collected from local indigenous plants or isolated molds, as well as other outdoor and indoor allergens in allergic patients in 6 different geographical areas in the Kingdom of Saudi Arabia (KSA), the United Arab Emirates, and Sudan. Materials and methods Four hundred ninety-two consecutive patients evaluated at different Allergy Clinics (276 women and 256 men; mean age, 30 years) participated in this study. The selection of indigenous allergens was based on research findings in different areas from Riyadh and adjoining areas. Indigenous raw material for pollen grains was collected from the desert near the capital city of Riyadh, KSA. The following plants were included: Chenopodium murale, Salsola imbricata, Rumex vesicarius, Ricinus communis, Artiplex nummularia, Amaranthus viridis, Artemisia monosperma, Plantago boissieri, and Prosopis juliflora. Indigenous molds were isolated from air sampling in Riyadh and grown to obtain the raw material. These included the following: Ulocladium spp., Penicillium spp., Aspergillus fumigatus, Cladosporium spp., and Alternaria spp. The raw material was processed under Good Manufacturing Practices for skin testing. Other commercially available outdoor (grass and tree pollens) and indoor (mites, cockroach, and cat dander) allergens were also tested. Results The highest sensitization to indigenous pollens was detected to C. murale (32%) in Khartoum (Sudan) and S. imbricata (30%) and P. juliflora (24%) in the Riyadh region. The highest sensitization to molds was detected in Khartoum, especially to Cladosporium spp. (42%), Aspergillus (40%), and Alternaria spp. (38%). Sensitization to mites was also very prevalent

  1. Airway obstruction secondary to rhinoscleroma during pregnancy.

    PubMed

    Armstrong, W B; Peskind, S P; Bressler, K L; Crockett, D M

    1995-11-01

    Dyspnea is a fairly common complaint during pregnancy. However, if one excludes allergic nasal congestion of pregnancy, upper airway obstruction is a distinctly uncommon cause of dyspnea in the pregnant patient. Three cases of laryngeal rhinoscleroma in pregnant women requiring tracheostomy for airway management are reported. All three delivered healthy infants vaginally. Postpartum, two of the three were successfully decannulated, while the third became pregnant again before decannulation was accomplished. Treatment options and a review of the literature are presented.

  2. A patient with allergic bronchopulmonary mycosis caused by Aspergillus fumigatus and Candida albicans.

    PubMed

    Wardhana; Datau, E A

    2012-10-01

    Allergic Bronchopulmonary Mycosis (ABPM) is an exagregated immunologic response to fungal colonization in the lower airways. It may cause by many kinds of fungal, but Aspergillus fumigatus is the most common cause of ABPM, although other Aspergillus and other fungal organisms, like Candida albicans, have been implicated. Aspergllus fumigatus and Candida albicans may be found as outdoor and indoor fungi, and cause the sensitization, elicitation of the disease pathology, and its clinical manifestations. Several diagnostic procedurs may be impicated to support the diagnosis of ABPM caused by Aspergillus fumigatus and Candida albicans. A case of allergic bronchopulmonary mycosis caused by Aspergillus fumigatus and Candida albicans in a 48 year old man was discussed. The patient was treated with antifungal, corticosteroids, and antibiotic for the secondary bacterial infection. The patient's condition is improved without any significant side effects. PMID:23314973

  3. Allergic Mechanisms in Eosinophilic Esophagitis

    PubMed Central

    Wechsler, Joshua B; Bryce, Paul J

    2014-01-01

    Paralleling the overall trend in allergic diseases, Eosinophilic Esophagitis is rapidly increasing in incidence. It is associated with food antigen-triggered, eosinophil-predominant inflammation and the pathogenic mechanisms have many similarities to other chronic atopic diseases, such as eczema and allergic asthma. Studies in animal models and from patients over the last 15 years have suggested that allergic sensitization leads to food-specific IgE and T-helper lymphocyte type 2 cells, both of which appear to contribute to the pathogenesis along with basophils, mast cells, and antigen-presenting cells. This review will outline our current understandings of the allergic mechanisms that drive eosinophilic esophagitis, drawing from clinical and translational studies in humans as well as experimental animal models. PMID:24813516

  4. Surgical Airway

    PubMed Central

    Patel, Sapna A; Meyer, Tanya K

    2014-01-01

    Close to 3% of all intubation attempts are considered difficult airways, for which a plan for a surgical airway should be considered. Our article provides an overview of the different types of surgical airways. This article provides a comprehensive review of the main types of surgical airways, relevant anatomy, necessary equipment, indications and contraindications, preparation and positioning, technique, complications, and tips for management. It is important to remember that the placement of a surgical airway is a lifesaving procedure and should be considered in any setting when one “cannot intubate, cannot ventilate”. PMID:24741501

  5. The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.

    PubMed

    Dudášová, A; Keir, S D; Parsons, M E; Molleman, A; Page, C P

    2013-06-01

    (-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders.

  6. Sinobronchial allergic aspergillosis with allergic bronchopulmonary aspergillosis: a less common co-existence

    PubMed Central

    Upadhyay, Rashmi; Kant, Surya; Prakash, Ved; Saheer, S

    2014-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder that is characterised by a hyper-responsiveness of the airways to Aspergillus fumigatus. Although several other fungi may also present with similar clinical conditions, Aspergillus remains the most common fungal pathogen causing airway infections. Co-existence of ABPA with allergic Aspergillus sinusitis (AAS) is an uncommon presentation. The concept of one airway/one disease justifies the co-existence of ABPA with AAS, but it does not always hold true. We report a case of a 35-year-old woman who presented with symptoms suggestive of bronchial asthma. On further investigation, the radiological pattern showed fleeting shadows and CT scan showed central cystic bronchiectatic changes characteristic of ABPA. The nasal secretions were investigated for the presence of Aspergillus and were found to be positive. Hence a diagnosis of ABPA with AAS was established. The patient was treated with oral steroids and antifungal drugs. PMID:25371437

  7. Allergic rhinitis and its impact on asthma update (ARIA 2008)--western and Asian-Pacific perspective.

    PubMed

    Pawankar, Ruby; Bunnag, Chaweewan; Chen, Yuzhi; Fukuda, Takeshi; Kim, You-Young; Le, Lan Thi Tuyet; Huong, Le Thi Thu; O'Hehir, Robyn E; Ohta, Ken; Vichyanond, Pakit; Wang, De-Yun; Zhong, Nanshan; Khaltaev, Nikolai; Bousquet, Jean

    2009-12-01

    The prevalence of allergic diseases such as allergic rhinitis (AR) and asthma is markedly increasing worldwide as societies adopt western life styles. Allergic sensitization is an important risk factor for asthma and AR, and asthma often co-exists with AR. An estimated 300 million people worldwide have asthma, about 50% of whom live in developing countries and about 400 million people suffer from AR. Yet, AR is often under-diagnosed and under-treated due to a lack of appreciation of the disease burden and its impact on quality of life, as well as its social impact at school and at the workplace. However, AR with or without asthma is a huge economic burden. Thus, there was clearly a need for a global evidence-based document which would highlight the interactions between the upper and lower airways including diagnosis, epidemiology, common risk factors, management and prevention. The Allergic Rhinitis and its Impact on Asthma (ARIA) document was first published in 2001 as a state-of-the-art guideline for the specialist, the general practitioner and other health care professionals. Subsequent new evidence regarding the pathomechanisms, new drugs and increased knowledge have resulted in the publication of the ARIA 2008 update. The present review summarizes the ARIA update with particular emphasis on the current status of AR and asthma in the Asia-Pacific region and discusses the Western and Asian perspective.

  8. Methods in assessment of airway reactivity in mice.

    PubMed

    Gold, Matthew; Blanchet, Marie-Renee

    2015-01-01

    Due to the wealth of reagents and transgenic strains available, mice have become one of the most commonly used model organisms for the study of allergic airway inflammation. One of the major hallmarks of the asthma phenotype in humans is reversible airflow obstruction, or airway hyper-responsiveness. However, the ability to confidently obtain useful physiological responses from such a small animal has presented a large technological challenge in murine studies. Recent advances have provided the technology to obtain lung mechanics through either the forced oscillation technique or plethysmography. Here we describe the utility of these measurements in mouse models of allergic airway inflammation and anaphylaxis. PMID:25388272

  9. The effect of house dust mite sensitization on lung size and airway caliber in symptomatic and nonsymptomatic preadolescent children: a community-based study in Poland.

    PubMed Central

    Jedrychowski, Wieslaw; Maugeri, Umberto; Jedrychowska-Bianchi, Iwona; Mróz, Elzbieta

    2002-01-01

    There are conflicting reports on the effects of atopy on lung function. The purpose of this study was to compare the effects of house mite (HM) atopy on lung function in subsamples of 12-year-old symptomatic and nonsymptomatic preadolescent children taken from the community sample. An additional objective of this study was to identify possible environmental determinants of HM skin reaction. We obtained questionnaire data on respiratory symptoms and skin-prick tests and performed spirometry on a subsample of 311 children of a birth cohort of children who have been followed over 3 years. Multivariate regression analysis showed progressive decrement of lung function indices (forced vital capacity, forced expiratory volume in 1 sec, and forced expiratory flow, midexpiratory phase) with increasing degree of HM atopy reflected by the skin reaction to HM allergens. The apparent association between the level of HM atopy and the lung function indices was highly significant in symptomatic individuals but insignificant in nonsymptomatic subjects. HM sensitization was significantly associated with mother's atopy. It occurred predominantly in boys and was related to the use of coal or gas for house heating. The effect of allergen sensitization on lung size and airway caliber confined to symptomatic subjects may reflect the inflammatory status of bronchial airways in the symptomatic subjects. PMID:12055047

  10. Neurology of allergic inflammation and rhinitis.

    PubMed

    Canning, Brendan J

    2002-05-01

    Afferent nerves, derived from the trigeminal ganglion, and postganglionic autonomic nerves, derived from sympathetic and parasympathetic ganglia expressing many different neurotransmitters, innervate the nose. Reflexes that serve to optimize the air-conditioning function of the nose by altering sinus blood flow, or serve to protect the nasal mucosal surface by mucus secretion, vasodilatation, and sneezing, can be initiated by a variety of stimuli, including allergen, cold air, and chemical irritation. Activation of nasal afferent nerves can also have profound effects on respiration, heart rate, blood pressure, and airway caliber (the diving response). Dysregulation of the nerves in the nose plays an integral role in the pathogenesis of allergic rhinitis. Axon reflexes can precipitate inflammatory responses in the nose, resulting in plasma extravasation and inflammatory cell recruitment, while allergic inflammation can produce neuronal hyper-responsiveness. Targeting the neuronal dysregulation in the nose may be beneficial in treating upper airway disease. PMID:11918862

  11. Overview on the pathomechanisms of allergic rhinitis

    PubMed Central

    Mori, Sachiko; Ozu, Chika; Kimura, Satoko

    2011-01-01

    Allergic rhinitis a chronic inflammatory disease of the upper airways that has a major impact on the quality of life of patients and is a socio-economic burden. Understanding the underlying immune mechanisms is central to developing better and more targeted therapies. The inflammatory response in the nasal mucosa includes an immediate IgE-mediated mast cell response as well as a latephase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including interleukin (IL)-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor and on-going allergic inflammation. Recent advances have suggested new pathways like local synthesis of IgE, the IgE-IgE receptor mast cell cascade in on-going allergic inflammation and the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33). In this review, we briefly review the conventional pathways in the pathophysiology of allergic rhinitis and then elaborate on the recent advances in the pathophysiology of allergic rhinitis. An improved understanding of the immune mechanisms of allergic rhinitis can provide a better insight on novel therapeutic targets. PMID:22053313

  12. Neurturin influences inflammatory responses and airway remodeling in different mouse asthma models.

    PubMed

    Mauffray, Marion; Domingues, Olivia; Hentges, François; Zimmer, Jacques; Hanau, Daniel; Michel, Tatiana

    2015-02-15

    Neurturin (NTN) was previously described for its neuronal activities, but recently, we have shown that this factor is also involved in asthma physiopathology. However, the underlying mechanisms of NTN are unclear. The aim of this study was to investigate NTN involvement in acute bronchial Th2 responses, to analyze its interaction with airway structural cells, and to study its implication in remodeling during acute and chronic bronchial inflammation in C57BL/6 mice. We analyzed the features of allergic airway inflammation in wild-type and NTN(-/-) mice after sensitization with two different allergens, OVA and house dust mite. We showed that NTN(-/-) dendritic cells and T cells had a stronger tendency to activate the Th2 pathway in vitro than similar wild-type cells. Furthermore, NTN(-/-) mice had significantly increased markers of airway remodeling like collagen deposition. NTN(-/-) lung tissues showed higher levels of neutrophils, cytokine-induced neutrophil chemoattractant, matrix metalloproteinase 9, TNF-α, and IL-6. Finally, NTN had the capacity to decrease IL-6 and TNF-α production by immune and epithelial cells, showing a direct anti-inflammatory activity on these cells. Our findings support the hypothesis that NTN could modulate the allergic inflammation in different mouse asthma models. PMID:25595789

  13. In vivo Regulation of the Allergic Response by the Interleukin 4 Receptor Alpha Chain Immunoreceptor Tyrosine-based Inhibitory Motif

    PubMed Central

    Tachdjian, Raffi; Khatib, Shadi Al; Schwinglshackl, Andreas; Kim, Hong Sook; Chen, Andrew; Blasioli, Julie; Mathias, Clinton; Kim, Hye-Young; Umetsu, Dale T.; Oettgen, Hans C.; Chatila, Talal A.

    2010-01-01

    Background Signaling by IL-4 and IL-13 via the IL-4 receptor alpha chain (IL-4Rα) plays a critical role in the pathology of allergic diseases. The IL-4Rα is endowed with an immunoreceptor tyrosine-based inhibitory motif (ITIM), centered on tyrosine 709 (Y709) in the cytoplasmic domain, that binds a number of regulatory phosphatases. The function of the ITIM in the in vivo regulation of IL-4R signaling remains unknown. Objective To determine the in vivo function of the IL-4Rα ITIM using mice in which the ITIM was inactivated by mutagenesis of the tyrosine Y709 residue into phenylalanine (F709). Methods F709 ITIM mutant mice were derived by knockin mutagenesis. Activation of intracellular signaling cascades by IL-4 and IL-13 was assessed by intracellular staining of phosphorylated signaling intermediates and by gene expression analysis. In vivo responses to allergic sensitization were assessed using models of allergic airway inflammation. Results The F709 mutation increased STAT6 phosphorylation by IL-4 and, disproportionately, by IL-13. This was associated with exaggerated Th2 polarization, enhanced alternative macrophage activation by IL-13, augmented basal and antigen-induced IgE responses and intensified allergen-induced eosinophilic airway inflammation and hyperreactivity. Conclusions These results point to a physiologic negative regulatory role for the Y709 ITIM in signaling via IL-4Rα, especially by IL-13. PMID:20392476

  14. Acute and chronic exposure to Tyrophagus putrescentiae induces allergic pulmonary response in a murine model

    PubMed Central

    Nuñez, Nailê Karine; dos Santos Dutra, Moisés; Barbosa, Gustavo Leivas; Morassutti, Alessandra Loureiro; de Souza, Rodrigo Godinho; Vargas, Mauro Henrique Moraes; Antunes, Géssica Luana; Silveira, Josiane Silva; da Silva, Guilherme Liberato; Pitrez, Paulo Márcio

    2016-01-01

    Background Tyrophagus putrescentiae (Tp) is a source of aeroallergen that causes allergic diseases. Objective To describe an acute and chronic murine model of allergic asthma with Tp extract with no systemic sensitization and no use of adjuvant. Methods Mites from dust sample were cultured and a raw extract was produced. Female BALB/c mice (6-8 weeks) were challenged intranasally with Tp extract or Dulbecco's phosphate-buffered saline, for 10 consecutive days (acute protocol) or for 6 weeks (chronic protocol). Twenty-four hours after the last intranasal challenge, bronchoalveolar lavage fluid (BALF) was performed for total and differential cells count, cytokine analysis, and eosinophil peroxidase activity. Lung tissue was also removed for histopathologic analysis. Results Tp extract has shown a significant increase in total cells count from BALF as well as an increase in absolute eosinophils count, eosinophil peroxidase activity, interleukin (IL)-5 and IL-13 levels, in both acute and chronic protocols. Peribronchovascular infiltrate, goblet cells hyperplasia and collagen deposition were shown in the airways of acute and chronic Tp-exposed mice. Conclusion Our data suggest that the intranasal exposure to Tp extract, with no systemic sensitization and no use of adjuvants, induces a robust allergic inflammation in the lungs of mice, in both acute and chronic models. Our Tp extract seems to be a potent allergen extract which may be used in asthma model studies. PMID:26844220

  15. Genetic variation influences immune responses in sensitive rats following exposure to TiO2 nanoparticles.

    PubMed

    Gustafsson, Asa; Jonasson, Sofia; Sandström, Thomas; Lorentzen, Johnny C; Bucht, Anders

    2014-12-01

    This study examines the immunological responses in rats following inhalation to titanium dioxide nanoparticles (TiO2 NPs), in naïve rats and in rats with induced allergic airway disease. The responses of two different inbred rat strains were compared: the Dark Aguoti (DA), susceptible to chronic inflammatory disorders, and the Brown Norwegian (BN), susceptible to atopic allergic inflammation. Naïve rats were exposed to an aerosol of TiO2 NPs once daily for 10 days. Another subset of rats was sensitized to the allergen ovalbumin (OVA) in order to induce airway inflammation. These sensitized rats were exposed to TiO2 NPs before and during the allergen challenge. Naïve rats exposed to TiO2 NPs developed an increase of neutrophils and lymphocytes in both rat strains. Airway hyperreactivity and production of inflammatory mediators typical of a T helper 1 type immune response were significantly increased, only in DA rats. Sensitization of the rats induced a prominent OVA-specific-IgE and IgG response in the BN rat while DA rats only showed an increased IgG response. Sensitized rats of both strains developed airway eosinophilia following allergen challenge, which declined upon exposure to TiO2 NPs. The level of neutrophils and lymphocytes increased upon exposure to TiO2 NPs in the airways of DA rats but remained unchanged in the airways of BN rats. In conclusion, the responses to TiO2 NPs were strain-dependent, indicating that genetics play a role in both immune and airway reactivity. DA rats were found to be higher responder compared to BN rats, both when it comes to responses in naïve and sensitized rats. The impact of genetically determined factors influencing the inflammatory reactions pinpoints the complexity of assessing health risks associated with nanoparticle exposures.

  16. Development of an experimental model of maternal allergic asthma during pregnancy.

    PubMed

    Clifton, Vicki L; Moss, Timothy J M; Wooldridge, Amy L; Gatford, Kathryn L; Liravi, Bahar; Kim, Dasom; Muhlhausler, Beverly S; Morrison, Janna L; Davies, Andrew; De Matteo, Robert; Wallace, Megan J; Bischof, Robert J

    2016-03-01

    Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 ± 1 days gestational age (term, ∼147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12%) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48% lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.

  17. Epithelial EGF receptor signaling mediates airway hyperreactivity and remodeling in a mouse model of chronic asthma.

    PubMed

    Le Cras, Timothy D; Acciani, Thomas H; Mushaben, Elizabeth M; Kramer, Elizabeth L; Pastura, Patricia A; Hardie, William D; Korfhagen, Thomas R; Sivaprasad, Umasundari; Ericksen, Mark; Gibson, Aaron M; Holtzman, Michael J; Whitsett, Jeffrey A; Hershey, Gurjit K Khurana

    2011-03-01

    Increases in the epidermal growth factor receptor (EGFR) have been associated with the severity of airway thickening in chronic asthmatic subjects, and EGFR signaling is induced by asthma-related cytokines and inflammation. The goal of this study was to determine the role of EGFR signaling in a chronic allergic model of asthma and specifically in epithelial cells, which are increasingly recognized as playing an important role in asthma. EGFR activation was assessed in mice treated with intranasal house dust mite (HDM) for 3 wk. EGFR signaling was inhibited in mice treated with HDM for 6 wk, by using either the drug erlotinib or a genetic approach that utilizes transgenic mice expressing a mutant dominant negative epidermal growth factor receptor in the lung epithelium (EGFR-M mice). Airway hyperreactivity (AHR) was assessed by use of a flexiVent system after increasing doses of nebulized methacholine. Airway smooth muscle (ASM) thickening was measured by morphometric analysis. Sensitization to HDM (IgG and IgE), inflammatory cells, and goblet cell changes were also assessed. Increased EGFR activation was detected in HDM-treated mice, including in bronchiolar epithelial cells. In mice exposed to HDM for 6 wk, AHR and ASM thickening were reduced after erlotinib treatment and in EGFR-M mice. Sensitization to HDM and inflammatory cell counts were similar in all groups, except neutrophil counts, which were lower in the EGFR-M mice. Goblet cell metaplasia with HDM treatment was reduced by erlotinib, but not in EGFR-M transgenic mice. This study demonstrates that EGFR signaling, especially in the airway epithelium, plays an important role in mediating AHR and remodeling in a chronic allergic asthma model.

  18. Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma.

    PubMed

    Mushaben, Elizabeth M; Brandt, Eric B; Hershey, Gurjit K Khurana; Le Cras, Timothy D

    2013-01-01

    The mammalian target of rapamycin (mTOR) plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM)-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections) and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4-6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR), inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4(+) T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4(+) T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established.

  19. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    SciTech Connect

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2012-02-15

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  20. Blockade of CD49d (alpha4 integrin) on intrapulmonary but not circulating leukocytes inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.

    PubMed Central

    Henderson, W R; Chi, E Y; Albert, R K; Chu, S J; Lamm, W J; Rochon, Y; Jonas, M; Christie, P E; Harlan, J M

    1997-01-01

    Immunized mice after inhalation of specific antigen have the following characteristic features of human asthma: airway eosinophilia, mucus and Th2 cytokine release, and hyperresponsiveness to methacholine. A model of late-phase allergic pulmonary inflammation in ovalbumin-sensitized mice was used to address the role of the alpha4 integrin (CD49d) in mediating the airway inflammation and hyperresponsiveness. Local, intrapulmonary blockade of CD49d by intranasal administration of CD49d mAb inhibited all signs of lung inflammation, IL-4 and IL-5 release, and hyperresponsiveness to methacholine. In contrast, CD49d blockade on circulating leukocytes by intraperitoneal CD49d mAb treatment only prevented the airway eosinophilia. In this asthma model, a CD49d-positive intrapulmonary leukocyte distinct from the eosinophil is the key effector cell of allergen-induced pulmonary inflammation and hyperresponsiveness. PMID:9399955

  1. Indirect airway challenges.

    PubMed

    Joos, G F; O'Connor, B; Anderson, S D; Chung, F; Cockcroft, D W; Dahlén, B; DiMaria, G; Foresi, A; Hargreave, F E; Holgate, S T; Inman, M; Lötvall, J; Magnussen, H; Polosa, R; Postma, D S; Riedler, J

    2003-06-01

    Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation before scuba diving. Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges, e.g. hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.

  2. Seasonal changes of proapoptotic soluble Fas ligand level in allergic rhinitis combined with asthma.

    PubMed

    Mezei, Györgyi; Lévay, Magdolna; Sepler, Zsuzsanna; Héninger, Erika; Kozma, Gergely Tibor; Cserháti, Endre

    2006-09-01

    The function of apoptosis is to eliminate unnecessary or dangerous cells. The balance between production and death is important in the control of cell numbers within physiological ranges. Cells involved in allergic reactions may have altered apoptosis. The aim of this study was to examine the seasonal changes of programmed cell death in children with pollen allergy. We measured serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL), and examined whether there was any correlation between soluble apoptosis markers and development of asthma and or rhinitis in children with pollen allergy. We examined two groups of patients with ragweed pollen allergy. The first group consisted of 17 children with 'rhinitis only'. The second group consisted of 16 children with 'asthma + rhinitis'. For seasonal analysis we pooled the two groups and termed this the 'ragweed sensitive' group (n = 33, 5-18 yr, 25 boys, eight girls). Measurements (sFas and sFasL) were taken during the ragweed pollen allergy season, while control measurements were performed during the symptom-free period. There was no difference in sFas levels measured during and after [1941 +/- 68, 1963 +/- 83 pg/ml (mean+/-s.e.m, respectively)] the pollen season in the 'ragweed sensitive' group. The sFasL level showed seasonal change, which was significantly higher (p = 0.0086) in the symptomatic period compared to the symptom-free state (99 +/- 13 and 53 +/- 16 pg/ml, respectively). There was a difference between the 'rhinitis only' and the 'asthma + rhinitis' groups in the measured parameters of apoptosis. Children having allergic rhinitis combined with asthma had a significantly (p = 0.03) higher sFas level in the symptom-free state than the 'rhinitis only' group did (2115 +/- 156 and 1820 +/- 52 pg/ml, respectively). During the allergic symptom state the sFasL level of the 'asthma + rhinitis' group was significantly higher (p = 0.025) than that of the 'rhinitis only' group (125 +/- 20 and 75 +/- 14 pg

  3. Allergic reactions (image)

    MedlinePlus

    Allergic reaction can be provoked by skin contact with poison plants, chemicals and animal scratches, as well as by ... dust, nuts and shellfish, may also cause allergic reaction. Medications such as penicillin and other antibiotics are ...

  4. Allergic reactions to rubber condoms.

    PubMed

    Rademaker, M; Forsyth, A

    1989-06-01

    With the increased use of condoms, contact dermatitis to rubber is being seen more often. To develop a rubber condom suitable for use by rubber sensitive people, a "hypoallergenic" condom, which is washed in ammonia to reduce the residues of rubber accelerators, has been manufactured. Fifty patients allergic to various rubber accelerators were patch tested with an ordinary condom and the new washed condom. Fifty patients undergoing routine patch test investigation who were not allergic to rubber were also tested as controls. Twenty two of the rubber sensitive patients had a positive reaction to the new rubber condom compared with four of the control patients. Washing rubber condoms in ammonia does not appear to reduce the residues of rubber accelerators sufficiently for their use by rubber sensitive people. A non-allergenic condom is required.

  5. Allergic contact sensitivity to quinophthalone.

    PubMed

    Komamura, H; Kozuka, T; Ishii, M; Yoshikawa, K; Iyoda, M

    1989-03-01

    A 73-year-old patient, diagnosed as having seborrheic dermatitis, was patch tested with his hair preparations. The hair stick gave a positive reaction. Among its ingredients, D & C Yellow No. 11, from 0.0001% to 0.1%, and perfume showed positive reactions. D & C Yellow No. 11 was found to consist only of quinophthalone by chemical analyses. The concentration of quinophthalone in the hair stick was determined as 9.41 ppm w/w by high-performance liquid chromatography.

  6. Dietary prevention of allergic diseases in infants and small children. Part II. Evaluation of methods in allergy prevention studies and sensitization markers. Definitions and diagnostic criteria of allergic diseases.

    PubMed

    Muraro, Antonella; Dreborg, Sten; Halken, Susanne; Høst, Arne; Niggemann, Bodo; Aalberse, Rob; Arshad, Syed H; von Berg, Andrea; Carlsen, Kai-Håkon; Duschén, Karel; Eigenmann, Philippe; Hill, David; Jones, Catherine; Mellon, Michael; Oldeus, Göran; Oranje, Arnold; Pascual, Cristina; Prescott, Susan; Sampson, Hugh; Svartengren, Magnus; Vandenplas, Yvan; Wahn, Ulrich; Warner, Jill A; Warner, John O; Wickman, Magnus; Zeiger, Robert S

    2004-06-01

    The role of primary prevention of allergic disease has been a matter of debate for the last 40 years. In order to shed some light into this issue a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. The design of observational and interventional studies was evaluated with relevance to the important factors influencing outcome of studies on allergy development/prevention. in this analysis the statements of evidence as defined by WHO were applied. Best evidence of recommendations are those fulfilling the criteria for statements category 1 and 2 and grade of recommendations A and B as proposed by WHO. This survey include target group for dietary prevention and methods and diagnostic criteria of atopic dermatitis, asthma and food allergy for prevention studies.

  7. Combination Therapy with Budesonide and Salmeterol in Experimental Allergic Inflammation.

    PubMed

    Pappová, L; Jošková, M; Kazimierová, I; Šutovská, M; Fraňová, S

    2016-01-01

    The aim of this study was to determinate bronchodilator, antitussive, and ciliomodulatory activity of inhaled combination therapy with budesonide and salmeterol, and to correlate the results with the anti-inflammatory effect. The experiments were performed using two models of allergic inflammation (21 and 28 days long sensitization with ovalbumine) in guinea pigs. The animals were treated daily by aerosols of budesonide (1 mM), salmeterol (0.17 mM), and a half-dose combination of the two drugs. Antitussive and bronchodilator activities were evaluated in vivo. The ciliary beat frequency (CBF) was assessed in vitro in tracheal brushed samples, and inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, and TNF-α) were determined in bronchoalveolar lavage fluid (BALF). We found that the combination therapy significantly decreased the number of cough efforts, airway reactivity, and the level of inflammatory cytokines in both models of allergic asthma. Three weeks long sensitization led to an increase in CBF and all three therapeutic approaches have shown a ciliostimulatory effect in order: salmeterol < budesonid < combination therapy. Four weeks long ovalbumine sensitization, on the other hand, decreased the CBF, increased IL-5, and decreased IL-13. In this case, only the combination therapy was able to stimulate the CBF. We conclude that a half-dose combination therapy of budesonide and salmeterol shows comparable antitussive, bronchodilator, and the anti-inflammatory effect to a full dose therapy with budesonide alone, but had a more pronounced stimulatory effect on the CBF. PMID:27329088

  8. Preventative Effect of an Herbal Preparation (HemoHIM) on Development of Airway Inflammation in Mice via Modulation of Th1/2 Cells Differentiation

    PubMed Central

    Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

    2013-01-01

    HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4+ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4+ T cells displayed increased Th1 (IFN-γ+ cell) as well as decreased Th2 (IL-4+ cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance. PMID:23844220

  9. Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

    PubMed

    Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

    2013-01-01

    HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance. PMID:23844220

  10. Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

    PubMed

    Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

    2013-01-01

    HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

  11. Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

    PubMed

    Dharajiya, Nilesh; Vaidya, Swapnil; Sinha, Mala; Luxon, Bruce; Boldogh, Istvan; Sur, Sanjiv

    2009-01-01

    According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE) using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1), Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1) Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2) Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation. PMID:20027288

  12. Immunotherapy of allergic contact dermatitis.

    PubMed

    Spiewak, Radoslaw

    2011-08-01

    The term 'immunotherapy' refers to treating diseases by inducing, enhancing or suppressing immune responses. As allergy is an excessive, detrimental immune reaction to otherwise harmless environmental substances, immunotherapy of allergic disease is aimed at the induction of tolerance toward sensitizing antigens. This article focuses on the historical developments, present state and future outlook for immunotherapy with haptens as a therapeutic modality for allergic contact dermatitis. Inspired by the effectiveness of immunotherapy in respiratory allergies, attempts were undertaken at curing allergic contact dermatitis by means of controlled administration of the sensitizing haptens. Animal and human experiments confirmed that tolerance to haptens can be induced most effectively when the induction of tolerance precedes attempted sensitization. In real life, however, therapy is sought by people who are already sensitized and an effective reversal of hypersensitivity seems more difficult to achieve. Decades of research on Rhus hypersensitivity led to a conclusion that immunotherapy can suppress Rhus dermatitis, however, only to a limited degree, for a short period of time, and at a high risk of side effects, which makes this method therapeutically unprofitable. Methodological problems with most available studies of immunotherapy of contact allergy to nickel make any definite conclusions impossible at this stage.

  13. Vagotomy reverses established allergen-induced airway hyperreactivity to methacholine in the mouse✩

    PubMed Central

    McAlexander, M. Allen; Gavett, Stephen H.; Kollarik, Marian; Undem, Bradley J.

    2016-01-01

    We evaluated the role of vagal reflexes in a mouse model of allergen-induced airway hyperreactivity. Mice were actively sensitized to ovalbumin then exposed to the allergen via inhalation. Prior to ovalbumin inhalation, mice also received intratracheally-instilled particulate matter in order to boost the allergic response. In control mice, methacholine (i.v.) caused a dose-dependent increase in respiratory tract resistance (RT) that only modestly decreased if the vagi were severed bilaterally just prior to the methacholine challenge. Sensitized and challenged mice, however, manifested an airway reactivity increase that was abolished by severing the vagi prior to methacholine challenge. In an innervated ex vivo mouse lung model, methacholine selectively evoked action potential discharge in a subset of distension-sensitive A-fibers. These data support the hypothesis that the major component of the increased airway reactivity in inflamed mice is due to a vagal reflex initiated by activation of afferent fibers, even in response to a direct (i.e., smooth muscle)-acting muscarinic agonist. PMID:25842220

  14. Allergic contact dermatitis to white petrolatum.

    PubMed

    Kang, Hee; Choi, Jun; Lee, Ai-Young

    2004-05-01

    White petrolatum is known for its nonsensitizing and nonirritating properties. Only a few cases of allergic contact dermatitis to white petrolatum have been reported. Although it is a rare event, the finding of contact sensitization to white petrolatum raises the potential problem of its usage of common topical agents or vehicles for patch testing. We herein report a case of allergic contact dermatitis to white petrolatum.

  15. Persistence of Serotonergic Enhancement of Airway Response in a Model of Childhood Asthma

    PubMed Central

    Moore, Brian D.; Hyde, Dallas M.; Miller, Lisa A.; Wong, Emily M.

    2014-01-01

    The persistence of airway hyperresponsiveness (AHR) and serotonergic enhancement of airway smooth muscle (ASM) contraction induced by ozone (O3) plus allergen has not been evaluated. If this mechanism persists after a prolonged recovery, it would indicate that early-life exposure to O3 plus allergen induces functional changes predisposing allergic individuals to asthma-related symptoms throughout life, even in the absence of environmental insult. A persistent serotonergic mechanism in asthma exacerbations may offer a novel therapeutic target, widening treatment options for patients with asthma. The objective of this study was to determine if previously documented AHR and serotonin-enhanced ASM contraction in allergic monkeys exposed to O3 plus house dust mite allergen (HDMA) persist after prolonged recovery. Infant rhesus monkeys sensitized to HDMA were exposed to filtered air (FA) (n = 6) or HDMA plus O3 (n = 6) for 5 months. Monkeys were then housed in a FA environment for 30 months. At 3 years, airway responsiveness was assessed. Airway rings were then harvested, and ASM contraction was evaluated using electrical field stimulation with and without exogenous serotonin and serotonin-subtype receptor antagonists. Animals exposed to O3 plus HDMA exhibited persistent AHR. Serotonin exacerbated the ASM contraction in the exposure group but not in the FA group. Serotonin subtype receptors 2, 3, and 4 appear to drive the response. Our study shows that AHR and serotonin-dependent exacerbation of cholinergic-mediated ASM contraction induced by early-life exposure to O3 plus allergen persist for at least 2.5 years and may contribute to a persistent asthma phenotype. PMID:24484440

  16. Persistence of serotonergic enhancement of airway response in a model of childhood asthma.

    PubMed

    Moore, Brian D; Hyde, Dallas M; Miller, Lisa A; Wong, Emily M; Schelegle, Edward S

    2014-07-01

    The persistence of airway hyperresponsiveness (AHR) and serotonergic enhancement of airway smooth muscle (ASM) contraction induced by ozone (O3) plus allergen has not been evaluated. If this mechanism persists after a prolonged recovery, it would indicate that early-life exposure to O3 plus allergen induces functional changes predisposing allergic individuals to asthma-related symptoms throughout life, even in the absence of environmental insult. A persistent serotonergic mechanism in asthma exacerbations may offer a novel therapeutic target, widening treatment options for patients with asthma. The objective of this study was to determine if previously documented AHR and serotonin-enhanced ASM contraction in allergic monkeys exposed to O3 plus house dust mite allergen (HDMA) persist after prolonged recovery. Infant rhesus monkeys sensitized to HDMA were exposed to filtered air (FA) (n = 6) or HDMA plus O3 (n = 6) for 5 months. Monkeys were then housed in a FA environment for 30 months. At 3 years, airway responsiveness was assessed. Airway rings were then harvested, and ASM contraction was evaluated using electrical field stimulation with and without exogenous serotonin and serotonin-subtype receptor antagonists. Animals exposed to O3 plus HDMA exhibited persistent AHR. Serotonin exacerbated the ASM contraction in the exposure group but not in the FA group. Serotonin subtype receptors 2, 3, and 4 appear to drive the response. Our study shows that AHR and serotonin-dependent exacerbation of cholinergic-mediated ASM contraction induced by early-life exposure to O3 plus allergen persist for at least 2.5 years and may contribute to a persistent asthma phenotype. PMID:24484440

  17. Tumor Necrosis Factor Alpha Inhibits L-Type Ca2+ Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway

    PubMed Central

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca2+ channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  18. Tumor Necrosis Factor Alpha Inhibits L-Type Ca(2+) Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway.

    PubMed

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María; Montaño, Luis M

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway.

  19. Tumor Necrosis Factor Alpha Inhibits L-Type Ca(2+) Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway.

    PubMed

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María; Montaño, Luis M

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  20. Ethyl pyruvate attenuates murine allergic rhinitis partly by decreasing high mobility group box 1 release

    PubMed Central

    Chen, Shan; Wang, Yanjun; Gong, Guoqing; Chen, Jianjun; Niu, Yongzhi

    2015-01-01

    High-mobility group box 1 (HMGB1) protein, a pro-inflammatory DNA-binding protein, meditates inflammatory responses through Toll-like receptor-4 signals and amplifies allergic inflammation by interacting with the receptor for advanced glycation end products. Previous studies have shown that HMGB1 is elevated in the nasal lavage fluids (NLF) of children suffering from allergic rhinitis (AR) and is associated with the severity of this disease. Furthermore, HMGB1 has been implicated in the pathogenesis of lower airway allergic diseases, such as asthma. Ethyl pyruvate (EP) has proven to be an effective anti-inflammatory agent for numerous airway diseases. Moreover, EP can inhibit the secretion of HMGB1. However, few studies have examined the effect of EP on AR. We hypothesized that HMGB1 plays an important role in the pathogenesis of AR and studied it using an AR mouse model. Forty BALB/c mice were divided into four groups: the control group, AR group, 50 mg/kg EP group, and 100 mg/kg EP group. The mice in the AR and EP administration groups received ovalbumin (OVA) sensitization and challenge, whereas those in the control group were given sterile saline instead of OVA. The mice in the EP administration group were given an intraperitoneal injection of EP 30 min before each OVA treatment. The number of nasal rubbings and sneezes of each mouse was counted after final treatment. Hematoxylin–eosin staining, AB-PAS staining, interleukin-4 and 13 in NLF, IgE, and the protein expression of HMGB1 were measured. Various features of the allergic inflammation after OVA exposure, including airway eosinophilia, Th-2 cytokine production, total IgE, and goblet cell hyperplasia were significantly inhibited by treatment with EP and the expression and release of HMGB1 were reduced after EP administration in a dose-dependent manner. These results indicate that HMGB1 is a potential therapeutic target of AR and that EP attenuates AR by decreasing HMGB1 expression. PMID:25681468

  1. Treating allergic rhinitis in pregnancy.

    PubMed

    Piette, Vincent; Daures, Jean-Pierre; Demoly, Pascal

    2006-05-01

    Numerous pregnant women suffer from allergic rhinitis, and particular attention is required when prescribing drugs to these patients. In addition, physiologic changes associated with pregnancy could affect the upper airways. Evidence-based guidelines on the management of allergic rhinitis have been published. Medication can be prescribed during pregnancy when the apparent benefit of the drug is greater than the apparent risk. Usually, there is at least one "safe" drug from each major class used to control symptoms. All glucocorticosteroids are teratogenic in animals but, when the indication is clear (for diseases possibly associated, such as severe asthma exacerbation), the benefit of the drug is far greater than the risk. Inhaled glucocorticosteroids (eg, beclomethasone or budesonide) have not been incriminated as teratogens in humans and are used by pregnant women who have asthma. A few H1-antihistamines can safely be used as well. Most oral decongestants (except pseudoephedrine) are teratogenic in animals. There are no such data available for intranasal decongestants. Finally, pregnancy is not considered to be a contraindication for the continuation of immunotherapy.

  2. Fragrance allergic contact dermatitis.

    PubMed

    Cheng, Judy; Zug, Kathryn A

    2014-01-01

    Fragrances are a common cause of allergic contact dermatitis in Europe and in North America. They can affect individuals at any age and elicit a spectrum of reactions from contact urticaria to systemic contact dermatitis. Growing recognition of the widespread use of fragrances in modern society has fueled attempts to prevent sensitization through improved allergen identification, labeling, and consumer education. This review provides an overview and update on fragrance allergy. Part 1 discusses the epidemiology and evaluation of suspected fragrance allergy. Part 2 reviews screening methods, emerging fragrance allergens, and management of patients with fragrance contact allergy. This review concludes by examining recent legislation on fragrances and suggesting potential additions to screening series to help prevent and detect fragrance allergy.

  3. An Allergic Lung Microenvironment Suppresses Carbon Nanotube-Induced Inflammasome Activation via STAT6-Dependent Inhibition of Caspase-1

    PubMed Central

    Shipkowski, Kelly A.; Taylor, Alexia J.; Thompson, Elizabeth A.; Glista-Baker, Ellen E.; Sayers, Brian C.; Messenger, Zachary J.; Bauer, Rebecca N.; Jaspers, Ilona; Bonner, James C.

    2015-01-01

    Background Multi-walled carbon nanotubes (MWCNTs) represent a human health risk as mice exposed by inhalation display pulmonary fibrosis. Production of IL-1β via inflammasome activation is a mechanism of MWCNT-induced acute inflammation and has been implicated in chronic fibrogenesis. Mice sensitized to allergens have elevated T-helper 2 (Th2) cytokines, IL-4 and IL-13, and are susceptible to MWCNT-induced airway fibrosis. We postulated that Th2 cytokines would modulate MWCNT-induced inflammasome activation and IL-1β release in vitro and in vivo during allergic inflammation. Methods THP-1 macrophages were primed with LPS, exposed to MWCNTs and/or IL-4 or IL-13 for 24 hours, and analyzed for indicators of inflammasome activation. C57BL6 mice were sensitized to house dust mite (HDM) allergen and MWCNTs were delivered to the lungs by oropharyngeal aspiration. Mice were euthanized 1 or 21 days post-MWCNT exposure and evaluated for lung inflammasome components and allergic inflammatory responses. Results Priming of THP-1 macrophages with LPS increased pro-IL-1β and subsequent exposure to MWCNTs induced IL-1β secretion. IL-4 or IL-13 decreased MWCNT-induced IL-1β secretion by THP-1 cells and reduced pro-caspase-1 but not pro-IL-1β. Treatment of THP-1 cells with STAT6 inhibitors, either Leflunomide or JAK I inhibitor, blocked suppression of caspase activity by IL-4 and IL-13. In vivo, MWCNTs alone caused neutrophilic infiltration into the lungs of mice 1 day post-exposure and increased IL-1β in bronchoalveolar lavage fluid (BALF) and pro-caspase-1 immuno-staining in macrophages and airway epithelium. HDM sensitization alone caused eosinophilic inflammation with increased IL-13. MWCNT exposure after HDM sensitization increased total cell numbers in BALF, but decreased numbers of neutrophils and IL-1β in BALF as well as reduced pro-caspase-1 in lung tissue. Despite reduced IL-1β mice exposed to MWCNTs after HDM developed more severe airway fibrosis by 21 days and

  4. Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma

    PubMed Central

    Sousa, A.; Pfister, R.; Christie, P. E.; Lane, S. J.; Nasser, S. M.; Schmitz-Schumann, M.; Lee, T. H.

    1997-01-01

    BACKGROUND: There are two isoforms of cyclo-oxygenase (COX), namely COX- 1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation. METHODS: The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX- 1, in asthmatic patients. There was no significant difference in the total number of cells staining for either COX-1 or COX-2 between subjects with ASA and NASA, but the number and percentage of mast cells that expressed COX-2 was significantly increased sixfold and twofold, respectively, in individuals with ASA. There was a mean fourfold increase in the percentage of COX-2 expressing cells that were mast cells in subjects with ASA and the number of eosinophils expressing COX- 2 was increased 2.5-fold in these subjects. CONCLUSION: COX-2-derived metabolites may play an essential part in the inflammatory processes present in asthmatic airways and development of drugs targeted at this isoenzyme may have therapeutic potential in the treatment of asthma. Mast cells and eosinophils may also have a central role in the pathology of aspirin-sensitive asthma. 


 PMID:9487340

  5. Treatment of allergic rhinitis during pregnancy.

    PubMed

    Demoly, Pascal; Piette, Vincent; Daures, Jean-Pierre

    2003-01-01

    Allergic rhinitis is a frequent problem during pregnancy. In addition, physiological changes associated with pregnancy can affect the upper airways. Evidence-based guidelines on the management of allergic rhinitis have recently been published, the most recent being the Allergic Rhinitis and its Impact on Asthma (ARIA)--World Health Organization consensus. Many pregnant women experience allergic rhinitis and particular attention is required when prescribing drugs to these patients. Medication can be prescribed during pregnancy when the apparent benefit of the drug is greater than the apparent risk. Usually, there is at least one drug from each major class that can be safely utilised to control symptoms. All glucocorticosteroids are teratogenic in animals but, when the indication is clear (for diseases possibly associated, such as severe asthma exacerbation), the benefit of the drug is far greater than the risk. Inhaled glucocorticosteroids (e.g. beclomethasone or budesonide) have not been incriminated as teratogens in humans and are used by pregnant women who have asthma. A few histamine H(1)-receptor antagonists (H(1)-antihistamines) can safely be used as well. Most oral decongestants (except pseudoephedrine) are teratogenic in animals. There are no such data available for intra-nasal decongestants. Finally, pregnancy is not considered as a contraindication for the continuation of allergen specific immunotherapy.

  6. Impaired induction of allergic lung inflammation by Alternaria alternata mutant MAPK homologue Fus3.

    PubMed

    Kim, Hee-Kyoo; Baum, Rachel; Lund, Sean; Khorram, Naseem; Yang, Siwy Ling; Chung, Kuang-Ren; Doherty, Taylor A

    2013-11-01

    The fungal allergen Alternaria alternata is associated with development of asthma, though the mechanisms underlying the allergenicity of Alternaria are largely unknown. The aim of this study was to identify whether the MAP kinase homologue Fus3 of Alternaria contributed to allergic airway responses. Wild-type (WT) and Fus3 deficient Alternaria extracts were given intranasal to mice. Extracts from Fus3 deficient Alternaria that had a functional copy of Fus3 introduced were also administered (CpFus3). Mice were challenged once and levels of BAL eosinophils and innate cytokines IL-33, thymic stromal lymphopoeitin (TSLP), and IL-25 (IL-17E) were assessed. Alternaria extracts or protease-inhibited extract were administered with (OVA) during sensitization prior to ovalbumin only challenges to determine extract adjuvant activity. Levels of BAL inflammatory cells, Th2 cytokines, and OX40-expressing Th2 cells as well as airway infiltration and mucus production were measured. WT Alternaria induced innate airway eosinophilia within 3 days. Mice given Fus3 deficient Alternaria were significantly impaired in developing airway eosinophilia that was largely restored by CpFus3. Further, BAL IL-33, TSLP, and Eotaxin-1 levels were reduced after challenge with Fus3 mutant extract compared with WT and CpFus3 extracts. WT and CpFus3 extracts demonstrated strong adjuvant activity in vivo as levels of BAL eosinophils, Th2 cytokines, and OX40-expressing Th2 cells as well as peribronchial inflammation and mucus production were induced. In contrast, the adjuvant activity of Fus3 extract or protease-inhibited WT extract was largely impaired. Finally, protease activity and Alt a1 levels were reduced in Fus3 mutant extract. Thus, Fus3 contributes to the Th2-sensitizing properties of Alternaria.

  7. Ligation of TLR7 on CD19(+) CD1d(hi) B cells suppresses allergic lung inflammation via regulatory T cells.

    PubMed

    Khan, Adnan R; Amu, Sylvie; Saunders, Sean P; Hams, Emily; Blackshields, Gordon; Leonard, Martin O; Weaver, Casey T; Sparwasser, Tim; Sheils, Orla; Fallon, Padraic G

    2015-06-01

    B cells have been described as having the capacity to regulate cellular immune responses and suppress inflammatory processes. One such regulatory B-cell population is defined as IL-10-producing CD19(+) CD1d(hi) cells. Previous work has identified an expansion of these cells in mice infected with the helminth, Schistosoma mansoni. Here, microarray analysis of CD19(+) CD1d(hi) B cells from mice infected with S. mansoni demonstrated significantly increased Tlr7 expression, while CD19(+) CD1d(hi) B cells from uninfected mice also demonstrated elevated Tlr7 expression. Using IL-10 reporter, Il10(-/-) and Tlr7(-/-) mice, we formally demonstrate that TLR7 ligation of CD19(+) CD1d(hi) B cells increases their capacity to produce IL-10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7-elicited CD19(+) CD1d(hi) B cells reduced airway inflammation and associated airway hyperresponsiveness. Using DEREG mice to deplete FoxP3(+) T regulatory cells in allergen-sensitized mice, we show that that TLR7-elicited CD19(+) CD1d(hi) B cells suppress airway hyperresponsiveness via a T regulatory cell dependent mechanism. These studies identify that TLR7 stimulation leads to the expansion of IL-10-producing CD19(+) CD1d(hi) B cells, which can suppress allergic lung inflammation via T regulatory cells.

  8. Ligation of TLR7 on CD19(+) CD1d(hi) B cells suppresses allergic lung inflammation via regulatory T cells.

    PubMed

    Khan, Adnan R; Amu, Sylvie; Saunders, Sean P; Hams, Emily; Blackshields, Gordon; Leonard, Martin O; Weaver, Casey T; Sparwasser, Tim; Sheils, Orla; Fallon, Padraic G

    2015-06-01

    B cells have been described as having the capacity to regulate cellular immune responses and suppress inflammatory processes. One such regulatory B-cell population is defined as IL-10-producing CD19(+) CD1d(hi) cells. Previous work has identified an expansion of these cells in mice infected with the helminth, Schistosoma mansoni. Here, microarray analysis of CD19(+) CD1d(hi) B cells from mice infected with S. mansoni demonstrated significantly increased Tlr7 expression, while CD19(+) CD1d(hi) B cells from uninfected mice also demonstrated elevated Tlr7 expression. Using IL-10 reporter, Il10(-/-) and Tlr7(-/-) mice, we formally demonstrate that TLR7 ligation of CD19(+) CD1d(hi) B cells increases their capacity to produce IL-10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7-elicited CD19(+) CD1d(hi) B cells reduced airway inflammation and associated airway hyperresponsiveness. Using DEREG mice to deplete FoxP3(+) T regulatory cells in allergen-sensitized mice, we show that that TLR7-elicited CD19(+) CD1d(hi) B cells suppress airway hyperresponsiveness via a T regulatory cell dependent mechanism. These studies identify that TLR7 stimulation leads to the expansion of IL-10-producing CD19(+) CD1d(hi) B cells, which can suppress allergic lung inflammation via T regulatory cells. PMID:25763771

  9. Bronchial biopsy evidence for leukocyte infiltration and upregulation of leukocyte-endothelial cell adhesion molecules 6 hours after local allergen challenge of sensitized asthmatic airways.

    PubMed Central

    Montefort, S; Gratziou, C; Goulding, D; Polosa, R; Haskard, D O; Howarth, P H; Holgate, S T; Carroll, M P

    1994-01-01

    We have examined the mucosal changes occurring in bronchial biopsies from six atopic asthmatics 5-6 h after local endobronchial allergen challenge and compared them with biopsies from saline-challenged segments from the same subjects at the same time point. All the subjects developed localized bronchoconstriction in the allergen-challenged segment and had a decrease in forced expiratory volume in 1 s (FEV1) (P < 0.01) and a decrease in their methacholine provocative concentration of agonist required to reduce FEV1 from baseline by 20% (P < 0.05) 24 h postchallenge. At 6 h we observed an increase in neutrophils (P = 0.03), eosinophils (P = 0.025), mast cells (P = 0.03), and CD3+ lymphocytes (P = 0.025), but not in CD4+ or CD8+ lymphocyte counts. We also detected an increase in endothelial intercellular adhesion molecule type 1 (P < 0.05) and E-selectin (P < 0.005), but not vascular cell adhesion molecule type 1 expression with a correlative increase in submucosal and epithelial LFA+ leucocytes (P < 0.01). Thus, in sensitized asthmatics, local endobronchial allergen instillation leads to an increased inflammatory cell infiltrate of the airway mucosa that involves upregulation of specific adhesion molecules expressed on the microvasculature. Images PMID:7512980

  10. Potential of Immunoglobulin A to Prevent Allergic Asthma

    PubMed Central

    Gloudemans, Anouk K.; Lambrecht, Bart N.; Smits, Hermelijn H.

    2013-01-01

    Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies. PMID:23690823

  11. Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.

    PubMed

    Muraro, Antonella; Lemanske, Robert F; Hellings, Peter W; Akdis, Cezmi A; Bieber, Thomas; Casale, Thomas B; Jutel, Marek; Ong, Peck Y; Poulsen, Lars K; Schmid-Grendelmeier, Peter; Simon, Hans-Uwe; Seys, Sven F; Agache, Ioana

    2016-05-01

    In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine. PMID:27155030

  12. Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.

    PubMed

    Muraro, Antonella; Lemanske, Robert F; Hellings, Peter W; Akdis, Cezmi A; Bieber, Thomas; Casale, Thomas B; Jutel, Marek; Ong, Peck Y; Poulsen, Lars K; Schmid-Grendelmeier, Peter; Simon, Hans-Uwe; Seys, Sven F; Agache, Ioana

    2016-05-01

    In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine.

  13. Allergic rhinitis and asthma: epidemiology and common pathophysiology.

    PubMed

    Khan, David A

    2014-01-01

    Allergic rhinitis and asthma are common diseases that frequently occur together. This concept has been referred to in the literature as united airway disease. Epidemiological studies have shown that the majority of patients with asthma have concomitant rhinitis and the presence of rhinitis is an increased risk factor for development of asthma. Patients with asthma and rhinitis share common physiology including heightened bronchial hyperresponsiveness and heightened reactivity to a variety of stimuli. Immunopathology of allergic rhinitis is also similar with the predominance of T-helper type 2 inflammation and tissue eosinophilia. Although several mechanisms have been proposed to explain the united airway theory, some of the best lines of evidence suggest that local airway inflammation can result in a systemic inflammatory response. Pharmacotherapeutic studies have shown that the treatment of rhinitis can improve asthma and vice versa. Nevertheless, systemic approaches such as immunotherapy lead to better outcomes for treating both disease states simultaneously. This article will focus on the data supporting the common epidemiology, shared pathophysiology, and therapeutic interventions aimed at allergic rhinitis and asthma as united airway diseases.

  14. BLOCKADE OF NERVE GROWTH FACTOR (NGF) RECEPTOR TRKA ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC INFLAMMATION

    EPA Science Inventory


    Recent studies have shown that asthmatics have increased levels of the neurotrophin, NGF, in their lungs. In addition, antibody blockade of NGF in mice attenuates airway resistance associated with allergic airway responses. DEP has been linked to asthma exacerbation in many c...

  15. Gedunin, a natural tetranortriterpenoid, modulates T lymphocyte responses and ameliorates allergic inflammation.

    PubMed

    Ferraris, Fausto K; Moret, Katelim Hottz; Figueiredo, Alexandre Bezerra Conde; Penido, Carmen; Henriques, Maria das Graças M O

    2012-09-01

    T lymphocytes are critical cells involved in allergy. Here, we report that the natural tetranortriterpenoid gedunin impaired allergic responses primarily by modulating T lymphocyte functions. The intraperitoneal (i.p.) administration of gedunin inhibited pleural leukocyte accumulation triggered by intra-pleural (i.pl.) challenge with ovalbumin (OVA) in previously sensitized C57BL/6 mice; this inhibition was primarily due to the impairment of eosinophil and T lymphocyte influx. Likewise, i.pl. pre-treatment with gedunin inhibited eosinophil and T lymphocyte migration into mouse lungs 24 h after OVA intra-nasal (i.n.) instillation. Pre-treatment with gedunin diminished the levels of CCL2, CCL3, CCL5, CCL11, Interleukin-5 and leukotriene B(4) at the allergic site. In vitro pre-treatment with gedunin failed to inhibit T lymphocyte adhesion and chemotaxis towards pleural washes recovered from OVA-challenged mice, suggesting that gedunin inhibits T lymphocyte migration in vivo via the inhibition of chemotactic mediators in situ. In vivo pre-treatment with gedunin reduced the numbers of CD69(+) and CD25(+) T lymphocytes in the pleura and CD25(+) cells in the thoracic lymph nodes 24 h after OVA i.pl. challenge. In accordance, in vitro treatment of T lymphocytes with gedunin inhibited α-CD3 mAb-induced expression of CD69 and CD25, proliferation, Interleukin-2 production and nuclear translocation of NFκB and NFAT. Notably, post-treatment of mice with gedunin reverted OVA-induced lung allergic inflammation by decreasing the T lymphocyte and eosinophil counts and the levels of eosinophilotactic mediators in bronchoalveolar lavage fluid. Our results demonstrate a remarkable anti-allergic effect of gedunin due to its capability to modulate T cell activation and trafficking into the airways. PMID:22709475

  16. Influence of the route of sensitization on local and systemic immune responses in a murine model of type I allergy.

    PubMed

    Repa, A; Wild, C; Hufnagl, K; Winkler, B; Bohle, B; Pollak, A; Wiedermann, U

    2004-07-01

    The pathophysiological and immunological characteristics of allergic immune responses are controlled by a variety of factors. We have studied the extent to which the route of sensitization influences allergen-specific IgE synthesis and local airway inflammation using a mouse model of allergic sensitization to the major birch pollen allergen Bet v 1. Sensitization of BALB/c mice with recombinant (r)Bet v 1 was performed using intraperitoneal (i.p.), subcutaneous (s.c.) or aerosol (a.s.) sensitization protocols. Mice were analysed for allergen-specific serum antibodies by ELISA and IgE-dependent basophil degranulation. Proliferative responses and cytokine production of splenocytes were measured upon Bet v 1 stimulation in vitro. Bronchoalveolar lavages were performed after airway challenge with aerosolized birch pollen extract for assessment of eosinophilic airway inflammation and local cytokine production in vivo. Highest allergen specific IgE levels and IgE-dependent basophil degranulation were achieved using the SC route. High IL-5 production by spleen and lung cells was associated with pronounced eosinophilia in bronchoalveolar lavages. After i.p. sensitization, despite giving the highest IgG levels, only low IgE levels, basophil degranulation and IL-5 production were seen. On the other hand, a.s. sensitization, resulting in the lowest systemic IgE and IL-5 levels, led to a comparably strong airway inflammation as the s.c. route. Our finding that the route of sensitization can result in a dissociation of local and systemic immune responses may contribute to a better understanding of the pathogenesis of allergic diseases and help to develop new treatment strategies.

  17. Construction of a Der p2-transgenic plant for the alleviation of airway inflammation.

    PubMed

    Lee, C C; Ho, H; Lee, K T; Jeng, S T; Chiang, B L

    2011-09-01

    In clinical therapy, the amount of antigen administered to achieve oral tolerance for allergic diseases is large, and the cost is a major consideration. In this study, we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy, and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen. We used plants (tobacco leaves) transgenic for the Dermatophagoides pteronyssinus 2 (Der p2) antigen to produce Der p2. Mice received total protein extract from Der p2 orally once per day over 6 days (days 0-2 and days 6-8). Mice were also sensitized and challenged with yeast-derived recombinant Der p2 (rDer p2), after which the mice were examined for airway hyper-responsiveness and airway inflammation. After sensitization and challenge with rDer p2, mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers, decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid, and eosinophil infiltration in the airway. In addition, hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants, and CD4(+)CD25(+)Foxp3(+) regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes. Furthermore, splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2. The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases.

  18. Allergen-encoded signals that control allergic responses

    PubMed Central

    Tung, Hui-Ying; Landers, Cameron; Li, Evan; Porter, Paul; Kheradmand, Farrah; Corry, David B.

    2016-01-01

    Purpose of review The purpose is to review the important recent advances made in how innate immune cells, microbes, and the environment contribute to the expression of allergic disease, emphasizing the allergen-related signals that drive allergic responses. Recent findings The last few years have seen crucial advances in how innate immune cells such as innate lymphoid cells group 2 and airway epithelial cells and related molecular pathways through organismal proteinases and innate immune cytokines, such as thymic stromal lymphopoietin, IL-25, and IL-33 contribute to allergy and asthma. Simultaneously with these advances, important progress has been made in our understanding of how the environment, and especially pathogenic organisms, such as bacteria, viruses, helminths, and especially fungi derived from the natural and built environments, either promote or inhibit allergic inflammation and disease. Of specific interest are how lipopolysaccharide mediates its antiallergic effect through the ubiquitin modifying factor A20 and the antiallergic activity of both helminths and protozoa. Summary Innate immune cells and molecular pathways, often activated by allergen-derived proteinases acting on airway epithelium and macrophages as well as additional unknown factors, are essential to the expression of allergic inflammation and disease. These findings suggest numerous future research opportunities and new opportunities for therapeutic intervention in allergic disease. PMID:26658015

  19. Severe upper airway obstruction during sleep.

    PubMed

    Bonekat, H William; Hardin, Kimberly A

    2003-10-01

    Few disorders may manifest with predominantly sleep-related obstructive breathing. Obstructive sleep apnea (OSA) is a common disorder, varies in severity and is associated with significant cardiovascular and neurocognitive morbidity. It is estimated that between 8 and 18 million people in the United States have at least mild OSA. Although the exact mechanism of OSA is not well-delineated, multiple factors contribute to the development of upper airway obstruction and include anatomic, mechanical, neurologic, and inflammatory changes in the pharynx. OSA may occur concomitantly with asthma. Approximately 74% of asthmatics experience nocturnal symptoms of airflow obstruction secondary to reactive airways disease. Similar cytokine, chemokine, and histologic changes are seen in both disorders. Sleep deprivation, chronic upper airway edema, and inflammation associated with OSA may further exacerbate nocturnal asthma symptoms. Allergic rhinitis may contribute to both OSA and asthma. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Treatment with CPAP therapy has also been shown to improve both daytime and nighttime peak expiratory flow rates in patients with concomitant OSA and asthma. It is important for allergists to be aware of how OSA may complicate diagnosis and treatment of asthma and allergic rhinitis. A thorough sleep history and high clinical suspicion for OSA is indicated, particularly in asthma patients who are refractory to standard medication treatments.

  20. Airway inflammation and IgE production induced by dust mite allergen-specific memory/effector Th2 cell line can be effectively attenuated by IL-35.

    PubMed

    Huang, Chiung-Hui; Loo, Evelyn Xiu-Ling; Kuo, I-Chun; Soh, Gim Hooi; Goh, Denise Li-Meng; Lee, Bee Wah; Chua, Kaw Yan

    2011-07-01

    CD4(+) memory/effector T cells play a central role in orchestrating the rapid and robust immune responses upon re-encounter with specific Ags. However, the immunologic mechanism(s) underlying these responses are still not fully understood. To investigate this, we generated an allergen (major house dust mite allergen, Blo t 5)-specific murine Th2 cell line that secreted IL-4, IL-5, IL-10, and IL-13, but not IL-9 or TNF-α, upon activation by the cognate Ag. These cells also exhibited CD44(high)CD62L(-) and CD127(+) (IL-7Rα(+)) phenotypes, which are characteristics of memory/effector T cells. Experiments involving adoptive transfer of this Th2 cell line in mice, followed by three intranasal challenges with Blo t 5, induced a dexamethasone-sensitive eosinophilic airway inflammation. This was accompanied by elevation of Th2 cytokines and CC- and CXC-motif chemokines, as well as recruitment of lymphocytes and polymorphic mononuclear cells into the lungs. Moreover, Blo t 5-specific IgE was detected 4 d after the last intranasal challenge, whereas elevation of Blo t 5-specific IgG1 was found at week two. Finally, pulmonary delivery of the pVAX-IL-35 DNA construct effectively downregulated Blo t 5-specific allergic airway inflammation, and i.m. injection of pVAX-IL-35 led to long-lasting suppression of circulating Blo t 5-specific and total IgE. This model provides a robust research tool to elucidate the immunopathogenic role of memory/effector Th2 cells in allergic airway inflammation. Our results suggested that IL-35 could be a potential therapeutic target for allergic asthma through its attenuating effects on allergen-specific CD4(+) memory/effector Th2 cell-mediated airway inflammation.

  1. Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice

    DOE PAGES

    Ballester, Marie; Jeanbart, Laura; de Titta, Alexandre; Nembrini, Chiara; Marsland, Benjamin J.; Hubbell, Jeffrey A.; Swartz, Melody A.

    2015-09-21

    An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatorymore » therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy.« less

  2. Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice

    SciTech Connect

    Ballester, Marie; Jeanbart, Laura; de Titta, Alexandre; Nembrini, Chiara; Marsland, Benjamin J.; Hubbell, Jeffrey A.; Swartz, Melody A.

    2015-09-21

    An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatory therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy.

  3. Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice

    PubMed Central

    Ballester, Marie; Jeanbart, Laura; de Titta, Alexandre; Nembrini, Chiara; Marsland, Benjamin J.; Hubbell, Jeffrey A.; Swartz, Melody A.

    2015-01-01

    An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatory therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy. PMID:26387548

  4. Current and future biomarkers in allergic asthma.

    PubMed

    Zissler, U M; Esser-von Bieren, J; Jakwerth, C A; Chaker, A M; Schmidt-Weber, C B

    2016-04-01

    Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthma. The number of genes related to allergic rhinitis and allergic asthma increases steadily; however, prognostic genes have not yet entered clinical application. We hypothesize that the combination of multiple genes may generate biomarkers with prognostic potential. The current review attempts to group more than 161 different potential biomarkers involved in respiratory inflammation to pave the way for future classifiers. The potential biomarkers are categorized into either epithelial or infiltrate-derived or mixed origin, epithelial biomarkers. Furthermore, surface markers were grouped into cell-type-specific categories. The current literature provides multiple biomarkers for potential asthma endotypes that are related to T-cell phenotypes such as Th1, Th2, Th9, Th17, Th22 and Tregs and their lead cytokines. Eosinophilic and neutrophilic asthma endotypes are also classified by epithelium-derived CCL-26 and osteopontin, respectively. There are currently about 20 epithelium-derived biomarkers exclusively derived from epithelium, which are likely to innovate biomarker panels as they are easy to sample. This article systematically reviews and categorizes genes and collects current evidence that may promote these biomarkers to become part of allergic rhinitis or allergic asthma classifiers with high prognostic value. PMID:26706728

  5. Epigenomics and allergic disease.

    PubMed

    Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

    2013-12-01

    Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment.

  6. Epigenomics and allergic disease

    PubMed Central

    Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

    2014-01-01

    Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment. PMID:24283882

  7. Modifications of plasma 5-HT concentrations during the allergic bronchoconstriction in guinea pigs.

    PubMed

    Arreola-Ramírez, José Luis; Vargas, Mario H; Manjarrez-Gutiérrez, Gabriel; Alquicira, Jesús; Gutiérrez, Julio; Córdoba, Guadalupe; Campos-Bedolla, Patricia; Segura-Medina, Patricia

    2013-09-01

    Several contractile mediators involved in the antigen-induced airway obstruction have been identified, but the role of 5-HT (5-hydroxytryptamine or serotonin) has been scantily investigated. In this work, the potential role of 5-HT in the allergic bronchoconstriction was evaluated through a pharmacological approach and plasma 5-HT measurement in blood samples from the right and left ventricles of anesthetized guinea-pigs. Intravenous 5-HT caused a dose-dependent increase of the lung resistance in anesthetized, nonsensitized guinea pigs. Likewise, in sensitized animals the antigenic challenge with ovalbumin also caused a transient bronchoconstriction (356 ± 60% the basal value), which was largely inhibited by the blockade of serotonergic receptors with methiothepin plus tropisetron (134 ± 10%, P = .007). Sensitized animals tended to have plasma 5-HT concentrations higher than nonsensitized controls, and shortly after the peak of the allergic bronchoconstriction the 5-HT levels in the left ventricle (blood flowing out from lungs) tended to be higher than in the right ventricle (blood entering the lungs), although data dispersion precluded the obtaining of statistical significance. Interestingly, the degree of bronchoconstriction highly correlated with the concentrations of 5-HT found in the left ventricle and measured either in platelet-rich plasma (r = 0.97 P = .007) or platelet-poor plasma (r = 0.97, P = .006). After the obstructive response subsided these correlations were lost, but now the degree of bronchoconstriction turned to be correlated with 5-HT concentration in platelet concentrate (r = 0.76, P = .03). In conclusion, our results suggested that 5-HT is actively released from lungs during the antigenic challenge and that this autacoid is involved in the generation of the airway obstruction.

  8. Preexposure to ozone blocks the antigen-induced late asthmatic response of the canine peripheral airways

    SciTech Connect

    Turner, C.R.; Kleeberger, S.R.; Spannhake, E.W. )

    1989-01-01

    The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels.

  9. Baseline Goblet Cell Mucin Secretion in the Airways Exceeds Stimulated Secretion over Extended Time Periods, and Is Sensitive to Shear Stress and Intracellular Mucin Stores

    PubMed Central

    Doyle, Sean P.; Nguyen, Kristine; Ribeiro, Carla M. P.; Vasquez, Paula A.; Forest, M. Gregory; Lethem, Michael I.; Dickey, Burton F.; Davis, C. William

    2015-01-01

    Airway mucin secretion studies have focused on goblet cell responses to exogenous agonists almost to the exclusion of baseline mucin secretion (BLMS). In human bronchial epithelial cell cultures (HBECCs), maximal agonist-stimulated secretion exceeds baseline by ~3-fold as measured over hour-long periods, but mucin stores are discharged completely and require 24 h for full restoration. Hence, over 24 h, total baseline exceeds agonist-induced secretion by several-fold. Studies with HBECCs and mouse tracheas showed that BLMS is highly sensitive to mechanical stresses. Harvesting three consecutive 1 h baseline luminal incubations with HBECCs yielded equal rates of BLMS; however, lengthening the middle period to 72 h decreased the respective rate significantly, suggesting a stimulation of BLMS by the gentle washes of HBECC luminal surfaces. BLMS declined exponentially after washing HBECCs (t1/2 = 2.75 h), to rates approaching zero. HBECCs exposed to low perfusion rates exhibited spike-like increases in BLMS when flow was jumped 5-fold: BLMS increased >4 fold, then decreased within 5 min to a stable plateau at 1.5–2-fold over control. Higher flow jumps induced proportionally higher BLMS increases. Inducing mucous hyperplasia in HBECCs increased mucin production, BLMS and agonist-induced secretion. Mouse tracheal BLMS was ~6-fold higher during perfusion, than when flow was stopped. Munc13-2 null mouse tracheas, with their defect of accumulated cellular mucins, exhibited similar BLMS as WT, contrary to predictions of lower values. Graded mucous metaplasia induced in WT and Munc13-2 null tracheas with IL-13, caused proportional increases in BLMS, suggesting that naïve Munc13-2 mouse BLMS is elevated by increased mucin stores. We conclude that BLMS is, [i] a major component of mucin secretion in the lung, [ii] sustained by the mechanical activity of a dynamic lung, [iii] proportional to levels of mucin stores, and [iv] regulated differentially from agonist-induced mucin

  10. Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

    PubMed Central

    Kelada, Samir N. P.

    2016-01-01

    Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene–environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design in which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics. PMID:27449512

  11. Brain-Derived Neurotrophic Factor in the Airways

    PubMed Central

    Prakash, Y.S.; Martin, Richard J.

    2014-01-01

    In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target. PMID:24560686

  12. Variation in airway responsiveness of male C57BL/6 mice from 5 vendors.

    PubMed

    Chang, Herng-Yu Sucie; Mitzner, Wayne; Watson, Julie

    2012-07-01

    Mice are now the most commonly used animal model for the study of asthma. The mouse asthma model has many characteristics of the human pathology, including allergic sensitization and airway hyperresponsiveness. Inbred strains are commonly used to avoid variations due to genetic background, but variations due to rearing environment are not as well recognized. After a change in mouse vendors and a switch from C57BL/6J mice to C57BL/6N mice, we noted significant differences in airway responsiveness between the substrains. To further investigate the effect of vendor, we tested C57BL/6N mice from 3 other vendors and found significant differences between several of the substrains. To test whether this difference was due to genetic drift or rearing environment, we purchased new groups of mice from all 5 vendors, bred them in separate vendor-specific groups under uniform environmental conditions, and tested male first generation (F1) offspring at 8 to 10 wk of age. These F1 mice showed no significant differences in airway responsiveness, indicating that the rearing environment rather than genetic differences was responsible for the initial variation in pulmonary phenotype. The environmental factors that caused the phenotypic variation are unknown. However, differences between vendor in feed components, bedding type, or microbiome could have contributed. Whatever the basis, investigators using mouse models of asthma should be cautious in comparing data from mice obtained from different vendors.

  13. Immunoregulatory Role of HLA-G in Allergic Diseases

    PubMed Central

    Contini, Paola; Negrini, Simone; Ciprandi, Giorgio; Puppo, Francesco

    2016-01-01

    Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. PMID:27413762

  14. Immunoregulatory Role of HLA-G in Allergic Diseases.

    PubMed

    Murdaca, Giuseppe; Contini, Paola; Negrini, Simone; Ciprandi, Giorgio; Puppo, Francesco

    2016-01-01

    Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. PMID:27413762

  15. Benzaldehyde suppresses murine allergic asthma and rhinitis.

    PubMed

    Jang, Tae Young; Park, Chang-Shin; Kim, Kyu-Sung; Heo, Min-Jeong; Kim, Young Hyo

    2014-10-01

    To evaluate the antiallergic effects of oral benzaldehyde in a murine model of allergic asthma and rhinitis, we divided 20 female BALB/c mice aged 8-10 weeks into nonallergic (intraperitoneally sensitized and intranasally challenged to normal saline), allergic (intraperitoneally sensitized and intranasally challenged to ovalbumin), and 200- and 400-mg/kg benzaldehyde (allergic but treated) groups. The number of nose-scratching events in 10 min, levels of total and ovalbumin-specific IgE in serum, differential counts of inflammatory cells in bronchoalveolar lavage (BAL) fluid, titers of Th2 cytokines (IL-4, IL-5, IL-13) in BAL fluid, histopathologic findings of lung and nasal tissues, and expressions of proteins involved in apoptosis (Bcl-2, Bax, caspase-3), inflammation (COX-2), antioxidation (extracellular SOD, HO-1), and hypoxia (HIF-1α, VEGF) in lung tissue were evaluated. The treated mice had significantly fewer nose-scratching events, less inflammatory cell infiltration in lung and nasal tissues, and lower HIF-1α and VEGF expressions in lung tissue than the allergic group. The number of eosinophils and neutrophils and Th2 cytokine titers in BAL fluid significantly decreased after the treatment (P<0.05). These results imply that oral benzaldehyde exerts antiallergic effects in murine allergic asthma and rhinitis, possibly through inhibition of HIF-1α and VEGF.

  16. Allergic Host Defenses

    PubMed Central

    Palm, Noah W.; Rosenstein, Rachel K.

    2012-01-01

    Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macro-parasites. Here we present arguments to suggest that allergic immunity plays an important role in host defense against noxious environmental substances, including venoms, hematophagous fluids, environmental xenobiotics and irritants. We argue that appropriately targeted allergic reactions are beneficial, although they can become detrimental when excessive. Furthermore, we suggest that allergic hypersensitivity evolved to elicit anticipatory responses and to promote avoidance of suboptimal environments. PMID:22538607

  17. Respiratory Allergic Disorders.

    PubMed

    Woloski, Jason Raymond; Heston, Skye; Escobedo Calderon, Sheyla Pamela

    2016-09-01

    Allergic asthma refers to a chronic reversible bronchoconstriction influenced by an allergic trigger, leading to symptoms of cough, wheezing, shortness of breath, and chest tightness. Allergic bronchopulmonary aspergillosis is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis, occurring when bronchi become colonized by Aspergillus species. The clinical picture is dominated by asthma complicated by recurrent episodes of bronchial obstruction, fever, malaise, mucus production, and peripheral blood eosinophilia. Hypersensitivity pneumonitis is a syndrome associated with lung inflammation from the inhalation of airborne antigens, such as molds and dust. PMID:27545731

  18. In vivo adenosine A(2B) receptor desensitization in guinea-pig airway smooth muscle: implications for asthma.

    PubMed

    Breschi, Maria Cristina; Blandizzi, Corrado; Fogli, Stefano; Martinelli, Cinzia; Adinolfi, Barbara; Calderone, Vincenzo; Camici, Marcella; Martinotti, Enrica; Nieri, Paola

    2007-12-01

    This study was aimed at characterizing the role of adenosine receptor subtypes in the contractility modulation of guinea-pig airway smooth muscle in normal and pathological settings. In vitro and in vivo experiments were performed by testing selective agonists and antagonists on isolated tracheal smooth muscle preparations and pulmonary inflation pressure, respectively, under normal conditions or following ovalbumin-induced allergic sensitization. In normal and sensitized animals, the adenosine A(2A)/A(2B) receptor agonist, NECA, evoked relaxing responses of isolated tracheal preparations precontracted with histamine, and such an effect was reversed by the adenosine A(2B) antagonist, MRS 1706, in the presence or in the absence of epithelium. The expression of mRNA coding for adenosine A(2B) receptors was demonstrated in tracheal specimens. In vitro desensitization with 100 microM NECA markedly reduced the relaxing effect of the agonist. In vivo NECA or adenosine administration to normal animals inhibited histamine-mediated bronchoconstriction, while these inhibitory effects no longer occurred in sensitized guinea-pigs. Adenosine plasma levels were significantly higher in sensitized than normal animals. In conclusion, our data demonstrate that: (i) adenosine A(2B) receptors are responsible for the relaxing effects of adenosine on guinea-pig airways; (ii) these receptors can undergo rapid adaptive changes that may affect airway smooth muscle responsiveness to adenosine; (iii) ovalbumin-induced sensitization promotes a reversible inactivation of adenosine A(2B) receptors which can be ascribed to homologous desensitization. These findings can be relevant to better understand adenosine functions in airways as well as mechanisms of action of asthma therapies targeting the adenosine system.

  19. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

    PubMed

    Morris, Abigail; Wang, Bo; Waern, Ida; Venkatasamy, Radhakrishnan; Page, Clive; Schmidt, Eric P; Wernersson, Sara; Li, Jin-Ping; Spina, Domenico

    2015-01-01

    Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/-) mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT) control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil) recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD) found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

  20. Association of Specific Immunoglobulin E to Staphylococcal Enterotoxin with Airway Hyperresponsiveness in Asthma Patients

    PubMed Central

    Kim, Seong Han; Yang, Seo Yeon; You, Jihong; Lee, Sang Bae; You, Jin; Chang, Yoon Soo; Kim, Hyung Jung; Ahn, Chul Min; Byun, Min Kwang; Park, Jung-Won

    2016-01-01

    Background Specific immunoglobulin E (IgE) sensitization to staphylococcal enterotoxin (SE) has been recently considered to be related to allergic disease, including asthma. Despite studies on specific IgE (sIgE) to SE and its relationship to asthma diagnosis and severity, the association of sIgE to SE with airway hyperresponsiveness (AHR) remains unclear. Methods We enrolled 81 asthma patients admitted to the Severance Hospital in Korea from March 1, 2013, to February 28, 2015 and retrospectively reviewed the electronic medical records of the enrolled subjects. The serum levels of sIgE to SE (A/B) of all subjects was measured using the ImmunoCAP 250 (Phadia) system with SE-sIgE positive defined as >0.10 kU/mL. Results The SE-sIgE level was not significantly correlated with asthma severity (forced expiratory volume in 1 second [FEV1], FEV1/forced vital capacity, sputum eosinophils, and serum eosinophils), whereas the SE-sIgE level in patients with positive AHR (mean±standard error of the mean, 0.606±0.273 kU/mL) was significantly higher than that in patients with negative AHR (0.062±0.015 kU/mL, p=0.034). In regression analysis, SE sensitization (sIgE to SE ≥0.010 kU/mL) was a significant risk factor for AHR, after adjustment for age, sex, FEV1, and sputum eosinophils (odds ratio, 7.090; 95% confidence interval, 1.180–42.600; p=0.032). Prevalence of SE sensitization was higher in patients with allergic rhinitis and non-atopic asthma patients, as compared to patients without allergic rhinitis and atopic asthma patients, respectively, but without statistical significance. Conclusion SE sensitization is significantly associated with AHR. PMID:27790282

  1. The effects of pregnancy on the exacerbation and development of maternal allergic respiratory disease.

    PubMed

    Pucheu-Haston, Cherie M; Copeland, Lisa B; Haykal-Coates, Najwa; Ward, Marsha D W

    2009-12-01

    The T-helper 2 (T(H)2) bias associated with pregnancy may predispose the pregnant mother to the development or exacerbation of allergic disease. To determine the effects of pregnancy on pre-existing maternal sensitization, we sensitized BALB/c mice before breeding by two intratracheal aspiration (IA) exposures to the fungal allergen, Metarhizium anisopliae crude antigen (MACA). Some mice also received three IA exposures to MACA on gestational days 11, 15, and 19. After weaning, all mice were challenged IA with MACA before killing. To determine the effects of pregnancy on susceptibility to future sensitization, naïve parous and nulliparous BALB/c mice were sensitized by three IA exposures to MACA or to Hank's buffered salt solution vehicle control. Pregnancy did not have a significant effect on individual inflammatory parameters (airway responsiveness to methacholine, total serum and bronchoalveolar lavage fluid (BALF) IgE, BALF total protein, lactate dehydrogenase activity, and total and differential cell counts) following allergen challenge in sensitized mice, regardless of post-breeding allergen exposure. In conclusion there was a weak inhibition of the overall response in mice exposed to allergen during pregnancy compared to identically treated nulliparous mice. In contrast, parous mice that did not encounter allergen post-breeding tended to have exacerbated responses. Parity had no significant impact on future susceptibility to sensitization. PMID:19845451

  2. Clara cells drive eosinophil accumulation in allergic asthma.

    PubMed

    Sonar, S S; Ehmke, M; Marsh, L M; Dietze, J; Dudda, J C; Conrad, M L; Renz, H; Nockher, W A

    2012-02-01

    Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.

  3. Biology of diesel exhaust effects on allergic pulmonary inflammation.

    PubMed

    Inoue, Ken-ichiro; Takano, Hirohisa

    2011-03-01

    Although the adverse health effects of diesel exhaust particles (DEP) have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions (pathological conditions) have not been fully identified. On the other hand, there exist hypersensitive subjects against particulate matters. In this review, we provide insights into the immunotoxicity of DEP as an aggravating factor in hypersusceptible subjects, especially those with allergic pulmonary diseases using our in vivo experimental model. In brief, we examined the effects of DEP on allergic asthma in vivo, and showed that repetitive pulmonary exposure to DEP has promoting effects on allergic airway inflammation, including adjuvanticity on Th2-milieu. Further, we propose a causal machinery regarding the adverse impacts, i.e., via inappropriate activation of antigen-presenting cells such as dendritic cells.

  4. Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.

    PubMed

    Álvarez-Santos, Mayra; Carbajal, Verónica; Tellez-Jiménez, Olivia; Martínez-Cordero, Erasmo; Ruiz, Victor; Hernández-Pando, Rogelio; Lascurain, Ricardo; Santibañez-Salgado, Alfredo; Bazan-Perkins, Blanca

    2016-10-01

    The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with β1 integrins (α1β1 and α2β1) in guinea pig. The putative role of β1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the β1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular β1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular β1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE-PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin-linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr(696) increased in asthma model. Our work suggests that β1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, β1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385-2396, 2016. © 2016 Wiley Periodicals, Inc.

  5. Allergic rhinitis during pregnancy.

    PubMed

    2016-04-01

    During pregnancy, the first-choice drugs for allergic rhinitis are nasal or oral "non-sedating" antihistamines without antimuscarinic activity, in particular cetirizine, or loratadine after the first trimester. PMID:27186624

  6. Allergic Contact Dermatitis

    MedlinePlus

    ... causes of allergic contact dermatitis include nickel, chromates, rubber chemicals, and topical antibiotic ointments and creams. Frequent ... construction workers who are in contact with cement. Rubber chemicals are found in gloves, balloons, elastic in ...

  7. Management of Allergic Rhinitis

    PubMed Central

    Sausen, Verra O.; Marks, Katherine E.; Sausen, Kenneth P.; Self, Timothy H.

    2005-01-01

    Allergic rhinitis is the most common chronic childhood disease. Reduced quality of life is frequently caused by this IgE-mediated disease, including sleep disturbance with subsequent decreased school performance. Asthma and exercise-induced bronchospasm are commonly seen concurrently with allergic rhinitis, and poorly controlled allergic rhinitis negatively affects asthma outcomes. Nonsedating antihistamines or intranasal azelastine are effective agents to manage allergic rhinitis, often in combination with oral decongestants. For moderate to severe persistent disease, intranasal corticosteroids are the most effiective agents. Some patients require concomitant intranasal corticosteroids and nonsedating antihistamines for optimal management. Other available agents include leukotriene receptor antagonists, intranasal cromolyn, intranasal ipratropium, specific immunotherapy, and anti-IgE therapy. PMID:23118635

  8. Allergic Rhinitis Quiz

    MedlinePlus

    ... allergic conjunctivitis (eye allergy). Is it true that mold spores can trigger eye allergy symptoms? True False ... allergy) are seasonal allergens such as pollen and mold spores. Indoor allergens such as dust mites and ...

  9. Allergic Rhinitis: Antihistamines

    MedlinePlus

    MENU Return to Web version Allergic Rhinitis | Antihistamines What are antihistamines? Antihistamines are medicines that help stop allergy symptoms, such as itchy eyes, sneezing and a runny nose. Sometimes, an antihistamine ...

  10. [Therapy of allergic rhinitis].

    PubMed

    Klimek, Ludger; Sperl, Annette

    2016-03-01

    If the avoidance of the provoking allergen is insufficient or not possible, medical treatment can be tried. Therapeutics of the first choice for the treatment of the seasonal and persistent allergic rhinitis are antihistamines and topical glucocorticoids. Chromones are less effective so they should only be used for adults with a special indication, for example during pregnancy. Beside the avoidance of the allergen the immunotherapy is the only causal treatment of allergic diseases. PMID:27120870

  11. Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation.

    PubMed

    Tran, Hai B; Lewis, Martin D; Tan, Lor Wai; Lester, Susan E; Baker, Leonie M; Ng, Jia; Hamilton-Bruce, Monica A; Hill, Catherine L; Koblar, Simon A; Rischmueller, Maureen; Ruffin, Richard E; Wormald, Peter J; Zalewski, Peter D; Lang, Carol J

    2012-01-01

    Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis. PMID:22523501

  12. Irritancy and Allergic Responses Induced by Exposure to the Indoor Air Chemical 4-Oxopentanal

    PubMed Central

    Anderson, Stacey E.; Franko, Jennifer; Jackson, Laurel G.; Wells, J. R.; Ham, Jason E.; Meade, B. J.

    2012-01-01

    Over the last two decades, there has been an increasing awareness regarding the potential impact of indoor air pollution on human health. People working in an indoor environment often experience symptoms such as eye, nose, and throat irritation. Investigations into these complaints have ascribed the effects, in part, to compounds emitted from building materials, cleaning/consumer products, and indoor chemistry. One suspect indoor air contaminant that has been identified is the dicarbonyl 4-oxopentanal (4-OPA). 4-OPA is generated through the ozonolysis of squalene and several high-volume production compounds that are commonly found indoors. Following preliminary workplace sampling that identified the presence of 4-OPA, these studies examined the inflammatory and allergic responses to 4-OPA following both dermal and pulmonary exposure using a murine model. 4-OPA was tested in a combined local lymph node assay and identified to be an irritant and sensitizer. A Th1-mediated hypersensitivity response was supported by a positive response in the mouse ear swelling test. Pulmonary exposure to 4-OPA caused a significant elevation in nonspecific airway hyperreactivity, increased numbers of lung-associated lymphocytes and neutrophils, and increased interferon-γ production by lung-associated lymph nodes. These results suggest that both dermal and pulmonary exposure to 4-OPA may elicit irritant and allergic responses and may help to explain some of the adverse health effects associated with poor indoor air quality. PMID:22403157

  13. Genetics of Allergic Diseases

    PubMed Central

    Ortiz, Romina A.; Barnes, Kathleen C.

    2015-01-01

    The allergic diseases are complex phenotypes for which a strong genetic basis has been firmly established. Genome-wide association studies (GWAS) has been widely employed in the field of allergic disease, and to date significant associations have been published for nearly 100 asthma genes/loci, in addition to multiple genes/loci for AD, AR and IgE levels, for which the overwhelming number of candidates are novel and have given a new appreciation for the role of innate as well as adaptive immune-response genes in allergic disease. A major outcome of GWAS in allergic disease has been the formation of national and international collaborations leading to consortia meta-analyses, and an appreciation for the specificity of genetic associations to sub-phenotypes of allergic disease. Molecular genetics has undergone a technological revolution, leading to next generation sequencing (NGS) strategies that are increasingly employed to hone in on the causal variants associated with allergic diseases. Unmet needs in the field include the inclusion of ethnically and racially diverse cohorts, and strategies for managing ‘big data’ that is an outcome of technological advances such as sequencing. PMID:25459575

  14. Zingiber mioga (Thunb.) Roscoe attenuates allergic asthma induced by ovalbumin challenge.

    PubMed

    Shin, Na-Rae; Shin, In-Sik; Jeon, Chan-Mi; Hong, Ju-Mi; Kwon, Ok-Kyoung; Kim, Hui-Seong; Oh, Sei-Ryang; Hahn, Kyu-Woung; Ahn, Kyung-Seop

    2015-09-01

    Zingiber mioga (Thunb.) Roscoe (ZM) is a traditional medicine, used to treat inflammatory diseases. The present study aimed to evaluate the inhibitory effects of ZM on the inflammatory response in lipopolysaccharide (LPS)‑stimulated RAW264.7 murine macrophage cells and in a mouse model of ovalbumin (OVA)‑induced allergic asthma. Mice received OVA sensitization on day 0 and 14, and were challenged with OVA between days 21 and 23. ZM was administered to the mice at a dose of 30 mg/kg, 1 h prior to OVA challenge. In LPS‑stimulated RAW264.7 cells, ZM significantly decreased nitric oxide (NO) and tumor necrosis factor (TNF)‑α production in a concentration‑dependent manner, and mRNA expression of inducible NO synthase (iNOS), TNF‑α and matrix metalloproteinase (MMP)‑9 was reduced. In addition, treatment with ZM decreased the inflammatory cell count in bronchoalveolar lavage fluid from the mice, and reduced the expression of interleukin (IL)‑4, IL‑5, IL‑13, eotaxin and immunoglobulin E. ZM also reduced airway hyperresponsiveness in OVA‑challenged mice, and attenuated the infiltration of inflammatory cells and mucus production in the airways, with a decrease in the expression of iNOS and MMP‑9 in lung tissue. In conclusion, the results of the present study indicate that ZM effectively inhibits inflammatory responses. Therefore, it may be that ZM has potential as a therapeutic agent for use in inflammatory diseases.

  15. [Allergic contact dermatitis due to prednicarbate].

    PubMed

    Senff, H; Kunz, R; Köllner, A; Kunze, J

    1991-01-01

    Two female patients developed an allergic contact dermatitis after using Dermatop cream and -ointment for several weeks. Patch tests were positive with the reagent prednicarbate itself. No cross reactions to other glucocorticosteroids were observed. Type-IV-sensitization to glucocorticosteroids should be considered if chronic dermatitis does not improve, or even becomes worse, in spite of adequate therapy. With regard to possible cross reactions or multiple sensitization, epicutaneous tests with other glucocorticosteroids are necessary.

  16. The role of autophagy in allergic inflammation: a new target for severe asthma

    PubMed Central

    Liu, Jing-Nan; Suh, Dong-Hyeon; Trinh, Hoang Kim Tu; Chwae, Yong-Joon; Park, Hae-Sim; Shin, Yoo Seob

    2016-01-01

    Autophagy has been investigated for its involvement in inflammatory diseases, but its role in asthma has been little studied. This study aimed to explore the possible role of autophagy and its therapeutic potential in severe allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) on days 0 and 14, followed by primary OVA challenge on days 28–30. The mice received a secondary 1 or 2% OVA challenge on days 44–46. After the final OVA challenge, the mice were assessed for airway responsiveness (AHR), cell composition and cytokine levels in bronchoalveolar lavage fluid (BALF). LC3 expression in lung tissue was measured by western blot and immunofluorescence staining. Autophagosomes were detected by electron microscopy. 3-Methyladenine (3-MA) treatment and Atg5 knockdown were applied to investigate the potential role of autophagy in allergic asthma mice. AHR, inflammation in BALF and LC3 expression in lung tissue were significantly increased in the 2% OVA-challenged mice compared with the 1% OVA-challenged mice (P<0.05). In addition, eosinophils showed prominent formation of autophagosomes and increased LC3 expression compared with other inflammatory cells in BALF and lung tissue. After autophagy was inhibited by 3-MA and Atg5 shRNA treatment, AHR, eosinophilia, interleukin (IL)-5 levels in BALF and histological inflammatory findings were much improved. Finally, treatment with an anti-IL-5 antibody considerably reduced LC3 II expression in lung homogenates. Our findings suggest that autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. PMID:27364893

  17. S-Nitrosoglutathione Reductase Inhibition Regulates Allergen-Induced Lung Inflammation and Airway Hyperreactivity

    PubMed Central

    Bassett, David J. P.; Bradley, Matthews O.; Jaffar, Zeina

    2013-01-01

    Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsivenes, mucus hypersecretion and tissue remodeling. S-Nitrosoglutathione reductase (GSNOR) is an alcohol dehydrogenase involved in the regulation of intracellular levels of S-nitrosothiols. GSNOR activity has been shown to be elevated in human asthmatic lungs, resulting in diminished S-nitrosothiols and thus contributing to increased airway hyperreactivity. Using a mouse model of allergic airway inflammation, we report that intranasal administration of a new selective inhibitor of GSNOR, SPL-334, caused a marked reduction in airway hyperreactivity, allergen-specific T cells and eosinophil accumulation, and mucus production in the lungs in response to allergen inhalation. Moreover, SPL-334 treatment resulted in a significant decrease in the production of the Th2 cytokines IL-5 and IL-13 and the level of the chemokine CCL11 (eotaxin-1) in the airways. Collectively, these observations reveal that GSNOR inhibitors are effective not only in reducing airway hyperresponsiveness but also in limiting lung inflammatory responses mediated by CD4+ Th2 cells. These findings suggest that the inhibition of GSNOR may provide a novel therapeutic approach for the treatment of allergic airway inflammation. PMID:23936192

  18. Quantification of airway deposition of intact and fragmented pollens.

    PubMed

    Horváth, Alpár; Balásházy, Imre; Farkas, Arpád; Sárkány, Zoltán; Hofmann, Werner; Czitrovszky, Aladár; Dobos, Erik

    2011-12-01

    Although pollen is one of the most widespread agents that can cause allergy, its airway transport and deposition is far from being fully explored. The objective of this study was to characterize the airway deposition of pollens and to contribute to the debate related to the increasing number of asthma attacks registered after thunderstorms. For the quantification of the deposition of inhaled pollens in the airways computer simulations were performed. Our results demonstrated that smaller and fragmented pollens may penetrate into the thoracic airways and deposit there, supporting the theory that fragmented pollen particles are responsible for the increasing incidence of asthma attacks following thunderstorms. Pollen deposition results also suggest that children are the most exposed to the allergic effects of pollens. Finally, pollens between 0.5 and 20 μm deposit more efficiently in the lung of asthmatics than in the healthy lung, especially in the bronchial region. PMID:21563012

  19. [Cytokines and allergic response].

    PubMed

    Guenounou, M

    1998-01-01

    Allergic reactions are under the control of several events that occur sequentially following allergen exposure, recognition by the immune system, IgE production and their interaction with effector cells bearing Fc epsilon receptors. The lymphocyte activation in response to allergens determines the intensity and the nature of the immune response. Cytokines produced by T (and non-T) cells are involved in the polarized development of the specific immune response. In particular, type 1 and type 2 cytokines are responsible for the control of the different steps during allergic reactions. Th2 cytokines and particularly IL4 are responsible for switching the immunoglobulin synthesis by B cells to IgE production. They also play a key role in the activation of effector cells that occurs following allergen interaction with fixed specific IgE and participate to the local inflammatory reaction. Cytokine profile determination appears to represent a helpful laboratory parameter in the understanding of the mechanisms underlying allergic diseases. The development of new technological tools may allow the use of cell activation parameters, and cytokine profiles determination in clinical biology. This review aims to analyze the involvement of the cytokine network in the mechanisms leading to IgE production and the involvement of cytokines in effector mechanisms of allergic reactions. It also analyses the potential use of cytokine profile determination for diagnosis purpose and survey of immune desensitization of allergic diseases.

  20. Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics**

    EPA Science Inventory

    Background Acute exacerbations in allergic asthmatics may lead to impaired ability to clear mucus from the airways, a key factor in asthma morbidity. Objective The purpose of this study was to determine the effect of inhaled house dust mite challenge on the regional deposition of...

  1. EFFECT OF SHORT TERM DIESEL EXHAUST EXPOSURE ON NASAL RESPONSES TO INFLUENZA IN ALLERGIC RHINITICS.

    EPA Science Inventory

    Introduction: Recently published data suggest that diesel exhaust (DE) has special impact on allergic inflammation, suppressing Th1 and augmenting Th2 responses to allergen via oxidant stress effects on airway cells. Exposures to particulate air pollutants including DE are also a...

  2. Genetics Home Reference: allergic asthma

    MedlinePlus

    ... Understand Genetics Home Health Conditions allergic asthma allergic asthma Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Asthma is a breathing disorder characterized by inflammation of ...

  3. Effect of Traffic-Related Air Pollution on Allergic Disease: Results of the Children's Health and Environmental Research

    PubMed Central

    Jung, Dal-Young; Kim, Hwan-Cheol; Kim, Jeong-Hee; Hwang, Seung-Sik; Lee, Ji-Young; Kim, Byoung-Ju; Hong, Yun-Chul; Hong, Soo-Jong; Kwon, Ho-Jang

    2015-01-01

    Purpose This study evaluated the relationship of living near to main roads to allergic diseases, airway hyperresponsiveness (AHR), allergic sensitization, and lung function in Korean children. Methods A total of 5,443 children aged 6-14 years from 33 elementary schools in 10 cities during 2005-2006 were included in a baseline survey of the Children's Health and Environmental Research. We assessed association of traffic-related air pollution (TAP) exposure with the distance to the nearest main road, total road length of main roads and the proportion of the main road area within the 200-m home area. Results Positive exposure-response relationships were found between the length of the main road within the 200-m home area and lifetime wheeze (adjusted prevalence ratio [PR] for comparison of the longest to the shortest length categories=1.24; 95% CIs, 1.04-1.47; P for trend=0.022) and diagnosed asthma (PR=1.42; 95% CIs, 1.08-1.86; P for trend=0.011). Living less than 75 m from the main road was significantly associated with lifetime allergic rhinitis (AR), past-year AR symptoms, diagnosed AR, and treated AR. The distance to the main road (P for trend=0.001), the length of the main road (P for trend=0.041), and the proportion of the main road area (P for trend=0.006) had an exposure-response relationship with allergic sensitization. A strong inverse association was observed between residential proximity to the main load and lung function, especially FEV1, FEV1/FVC, and FEF25-75. The length of the main road and the proportion of the main road area were associated with reduced FEV1 in schoolchildren. Conclusions The results of this study suggest that exposure to traffic-related air pollution may be associated with increased risk of asthma, AR, and allergic sensitization, and with reduced lung function in schoolchildren. PMID:25936911

  4. Evaluation of allergic response using dynamic thermography

    NASA Astrophysics Data System (ADS)

    Rokita, E.; Rok, T.; Tatoń, G.

    2015-03-01

    Skin dynamic termography supplemented by a mathematical model is presented as an objective and sensitive indicator of the skin prick test result. Termographic measurements were performed simultaneously with routine skin prick tests. The IR images were acquired every 70 s up to 910 s after skin prick. In the model histamine is treated as the principal mediator of the allergic reaction. Histamine produces vasolidation and the engorged vessels are responsible for an increase in skin temperature. The model parameters were determined by fitting the analytical solutions to the spatio-temporal distributions of the differences between measured and baseline temperatures. The model reproduces experimental data very well (coefficient of determination = 0.805÷0.995). The method offers a set of parameters to describe separately skin allergic reaction and skin reactivity. The release of histamine after allergen injection is the best indicator of allergic response. The diagnostic parameter better correlates with the standard evaluation of a skin prick test (correlation coefficient = 0.98) than the result of the thermographic planimetric method based on temperature and heated area determination (0.81). The high sensitivity of the method allows for determination of the allergic response in patients with the reduced skin reactivity.

  5. Emergency airway puncture

    MedlinePlus

    Emergency airway puncture is the placement of a hollow needle through the throat into the airway. It ... efforts to assist with breathing have failed. A hollow needle or tube can be inserted into the ...

  6. Local Allergic Rhinitis.

    PubMed

    Campo, Paloma; Salas, María; Blanca-López, Natalia; Rondón, Carmen

    2016-05-01

    This review focuses on local allergic rhinitis, a new phenotype of allergic rhinitis, commonly misdiagnosed as nonallergic rhinitis. It has gained attention over last decade and can affect patients from all countries, ethnic groups and ages, impairing their quality of life, and is frequently associated with conjunctivitis and asthma. Diagnosis is based on clinical history, the demonstration of a positive response to nasal allergen provocation test and/or the detection of nasal sIgE. A positive basophil activation test may support the diagnosis. Recent studies have demonstrated that allergen immunotherapy is an effective immune-modifying treatment, highlighting the importance of early diagnosis. PMID:27083105

  7. Allergy to nickel or cobalt: tolerance to nickel and cobalt samples in man and in the guinea pig allergic or sensitized to these metals.

    PubMed

    Cavelier, C; Foussereau, J; Gille, P; Zissu, D

    1989-08-01

    The aim of this study was to evaluate, in animals and humans sensitive to nickel or cobalt, the tolerance to manufactured metal samples of nickel and cobalt of a defined metallographic structure, plated or not with a layer of chrome or copper/chrome of a determined thickness. Under the defined experimental conditions, a guinea pig sensitized to one metal (nickel or cobalt) was intolerant to both metals (nickel and cobalt). A plating of chrome or copper/chrome did not act as a protection. In the human, it was not the same: the tolerance to metal samples was determined by the specific sensitivity. A plating of chrome or copper/chrome did not act as protection.

  8. Volatile Organic Compounds Contribute to Airway Hyperresponsiveness

    PubMed Central

    Jang, An-Soo; Choi, Inseon-S; Koh, Young-Il

    2007-01-01

    Background Volatile organic compounds (VOCs) in concentrations found in both the work and home environments may influence lung function. We investigated the prevalence of airway responsiveness in workers exposed to VOCs. Methods We used allergic skin tests, nonspecific airway hyperresponsiveness testing and questionnaires to study twenty exposed workers and twenty-seven control subjects. Atopy was defined as a reactor who showed >3+ response to one or more allergens on the skin prick tests. Airway hyperresponsiveness (BRindex) was defined as log [% fall of FEV1/ log (last concentration of methacholine) +10]. Results The VOC exposed workers, in comparison with the control subjects, tended to have a higher BRindex (1.19±0.07 vs. 1.15±0.08, respectively). Workers exposed to VOCs with atopy or smoker, as compared with the workers exposed to VOCs with non-atopy and who were non-smokers and the control subjects with non-atopy and who were non-smokers, had a significantly higher BRindex (1.20±0.05 vs. 1.14±0.06 vs. 1.10±0.03, respectively p<0.05). The BRindex was not correlated with atopy, the smoking status or the duration of VOC exposure. Conclusions These findings suggest that VOCs may act as a contributing factor of airway hyperresponsiveness in workers exposed to VOCs. PMID:17427638

  9. The activity of recent anti-allergic drugs in the treatment of seasonal allergic rhinitis.

    PubMed

    Wang, D; Clement, P; Smitz, J; De Waele, M

    1996-01-01

    Two experiments were performed during the pollen season to study the activity of different antiallergic drugs in the treatment of seasonal allergic rhinitis. Nasal allergen challenge (NAC) was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction during the season. The first study assessed the effect of H1 (Cetirizine 10 mg a day) and of a combination of H1 (Cetirizine 10 mg) plus H2 (Cimetidine 800 mg a day) antagonists on nasal symptoms, mediator release and eosinophil count in a group of 16 patients with seasonal allergic rhinitis. During the same season a second study compared in a randomized way (2 parallel groups) the effect of Budesonide (Rhinocort Aqua) and Azelastine (Allergodil nasal spray) in a group of 14 patients. Results showed that both antihistamines, applied topically of dosed orally, reduced sneezing even when significant increases of histamine concentration in nasal secretions were evidenced immediately after NAC. When a combination of Cetirizine and Cimetidine was administered, a significant (p < 0.01) reduction of nasal airway resistance and increase of nasal airflow after NAC were demonstrated as well. In addition, topical application of Budesonide showed a strong (p < 0.01) effect on the infiltration and activation of eosinophils during the season, and on tryptase release after NAC. These effects lasted at least for one week after therapy. PMID:8669268

  10. The activity of recent anti-allergic drugs in the treatment of seasonal allergic rhinitis.

    PubMed

    Wang, D; Clement, P; Smitz, J; De Waele, M

    1996-01-01

    Two experiments were performed during the pollen season to study the activity of different antiallergic drugs in the treatment of seasonal allergic rhinitis. Nasal allergen challenge (NAC) was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction during the season. The first study assessed the effect of H1 (Cetirizine 10 mg a day) and of a combination of H1 (Cetirizine 10 mg) plus H2 (Cimetidine 800 mg a day) antagonists on nasal symptoms, mediator release and eosinophil count in a group of 16 patients with seasonal allergic rhinitis. During the same season a second study compared in a randomized way (2 parallel groups) the effect of Budesonide (Rhinocort Aqua) and Azelastine (Allergodil nasal spray) in a group of 14 patients. Results showed that both antihistamines, applied topically of dosed orally, reduced sneezing even when significant increases of histamine concentration in nasal secretions were evidenced immediately after NAC. When a combination of Cetirizine and Cimetidine was administered, a significant (p < 0.01) reduction of nasal airway resistance and increase of nasal airflow after NAC were demonstrated as well. In addition, topical application of Budesonide showed a strong (p < 0.01) effect on the infiltration and activation of eosinophils during the season, and on tryptase release after NAC. These effects lasted at least for one week after therapy.

  11. SKIN SENSITIZATION AND ALLERGIC CONTACT DERMATITIS (BASIC COURSE): THE GLOBAL REGULATORY ENVIRONMENT - CONTINUING EDUCATION COURSE; 1 OF 4 SPEAKERS FOR AN SOT BASIC COURSE

    EPA Science Inventory

    New regulations have emerged in recent years giving guidance on how best to conduct skin sensitization testing on new chemical entities. For example, recently The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in the U.S. and the European Ce...

  12. Careers in Airway Science.

    ERIC Educational Resources Information Center

    Federal Aviation Administration (DOT), Washington, DC.

    The Federal Aviation Administration (FAA) has initiated the Airway Science curriculum as a method of preparing the next generation of aviation technicians and managers. This document: (1) discusses the FAA's role in the Airway Science program; (2) describes some of the career fields that FAA offers to Airway Science graduates (air traffic control…

  13. Human mesenchymal stem cells resolve airway inflammation, hyperreactivity, and histopathology in a mouse model of occupational asthma.

    PubMed

    Martínez-González, Itziar; Cruz, Maria-Jesús; Moreno, Rafael; Morell, Ferran; Muñoz, Xavier; Aran, Josep M

    2014-10-01

    Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history of the disease. We evaluated the ability of human adipose-tissue-derived mesenchymal stem cells (hASCs), either unmodified or engineered to secrete the IL-33 decoy receptor sST2, to attenuate the inflammatory and respiratory symptoms in a previously validated mouse model of OA to ammonium persulfate (AP). Twenty-four hours after a dermal AP sensitization and intranasal challenge regimen, the animals received intravenously 1 × 10(6) cells (either hASCs or hASCs overexpressing sST2) or saline and were analyzed at 1, 3, and 6 days after treatment. The infused hASCs induced an anti-inflammatory and restorative program upon reaching the AP-injured, asthmatic lungs, leading to early reduction of neutrophilic inflammation and total IgE production, preserved alveolar architecture with nearly absent lymphoplasmacytic infiltrates, negligible smooth muscle hyperplasia/hypertrophy in the peribronchiolar areas, and baseline airway hyperreactivity (AHR) to methacholine. Local sST2 overexpression barely increased the substantial efficacy displayed by unmodified hASCs. Thus, hASCs may represent a viable multiaction therapeutic capable to adequately respond to the AP-injured lung environment by resolving inflammation, tissue remodeling, and bronchial hyperresponsiveness typical of OA. PMID:24798370

  14. Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

    PubMed Central

    Martínez-González, Itziar; Moreno, Rafael; Morell, Ferran; Muñoz, Xavier

    2014-01-01

    Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history of the disease. We evaluated the ability of human adipose-tissue-derived mesenchymal stem cells (hASCs), either unmodified or engineered to secrete the IL-33 decoy receptor sST2, to attenuate the inflammatory and respiratory symptoms in a previously validated mouse model of OA to ammonium persulfate (AP). Twenty-four hours after a dermal AP sensitization and intranasal challenge regimen, the animals received intravenously 1×106 cells (either hASCs or hASCs overexpressing sST2) or saline and were analyzed at 1, 3, and 6 days after treatment. The infused hASCs induced an anti-inflammatory and restorative program upon reaching the AP-injured, asthmatic lungs, leading to early reduction of neutrophilic inflammation and total IgE production, preserved alveolar architecture with nearly absent lymphoplasmacytic infiltrates, negligible smooth muscle hyperplasia/hypertrophy in the peribronchiolar areas, and baseline airway hyperreactivity (AHR) to methacholine. Local sST2 overexpression barely increased the substantial efficacy displayed by unmodified hASCs. Thus, hASCs may represent a viable multiaction therapeutic capable to adequately respond to the AP-injured lung environment by resolving inflammation, tissue remodeling, and bronchial hyperresponsiveness typical of OA. PMID:24798370

  15. Effect of dexamethasone and Nigella sativa on inducible nitric oxide synthase in the lungs of a murine model of allergic Asthma.

    PubMed

    Abdel-Aziz, Mohamed; Abass, Ayman; Zalata, Khaled; Abd Al-Galel, Tarek; Allam, Umamma; Karrouf, Gamal

    2014-10-01

    The aim of this study was to investigate the effects of Nigella sativa (NS) fixed oil in comparison to dexamethasone (Dex) on inducible nitric oxide synthase (iNOS), peripheral blood eosinophils (PBE), allergen specific serum IgG1 and interleukins and airway inflammation in a murine model of allergic asthma. Thirty-one mice were divided into four groups. Group I (n = 6) served as the control group. Group II (n = 10) mice were sensitized intraperitoneally and challenged intratracheally with cone albumin with no treatment. Group III(n = 6) mice were sensitized, challenged, and treated with Dex for 17 days starting at 24 hours after the first challenge. Group IV (n = 9) mice were sensitized, challenged, and treated with NS fixed oil for 17 days as well. For all groups, the following procedures were carried out: immunohistochemical study of iNOS in lung tissues, detection of PBE percentage, and histopathological examination of lung tissues for inflammatory cells. Lung tissue iNOS expression increased in sensitized, non-treated mice compared with controls, but this increase was not significant. NS fixed oil treatment significantly reduced PBE and lung inflammation but did not significantly reduce lung tissue iNOS expression compared with the control group. These effects were comparable to the effects of Dex. These results suggest that Nigella sativa exhibits immunomodulatory and anti-inflammatory effect which may be useful for treatment of allergic asthma. PMID:25150073

  16. Targeting TSLP With shRNA Alleviates Airway Inflammation and Decreases Epithelial CCL17 in a Murine Model of Asthma

    PubMed Central

    Chen, Yi-Lien; Chiang, Bor-Luen

    2016-01-01

    Airway epithelium defends the invasion from microorganisms and regulates immune responses in allergic asthma. Thymic stromal lymphopoietin (TSLP) from inflamed epithelium promotes maturation of dendritic cells (DCs) to prime Th2 responses via CCL17, which induces chemotaxis of CD4+ T cells to mediate inflammation. However, few studies have investigated the regulation of epithelial CCL17. In this study, we used shRNA against TSLP to clarify the role of TSLP in the airway inflammation and whether TSLP affects the airway inflammation via epithelial CCL17. Specific shTSLP was delivered by lentivirus and selected by the knockdown efficiency. Allergic mice were intratracheally pretreated with the lentivirus and followed by intranasal ovalbumin (OVA) challenges. The sera antibody levels, airway inflammation, airway hyper-responsiveness (AHR), cytokine levels in bronchoalveolar lavage fluids, and CCL17 expressions in lungs were determined. In vivo, TSLP attenuation reduced the AHR, decreased the airway inflammation, inhibited the maturations of DCs, and suppressed the migration of T cells. Furthermore, the expression of CCL17 was particularly decreased in bronchial epithelium. In vitro, CCL17 induction was regulated by TSLP. In conclusion, TSLP might coordinate airway inflammation partially via CCL17-mediated responses and this study provides the vital utility of TSLP to develop the therapeutic approach in allergic airway inflammation. PMID:27138176

  17. Periostin in allergic inflammation.

    PubMed

    Izuhara, Kenji; Arima, Kazuhiko; Ohta, Shoichiro; Suzuki, Shoichi; Inamitsu, Masako; Yamamoto, Ken-ichi

    2014-06-01

    Periostin, an extracellular matrix protein belonging to the fasciclin family, has been shown to play a critical role in the process of remodeling during tissue/organ development or repair. Periostin functions as a matricellular protein in cell activation by binding to their receptors on cell surface, thereby exerting its biological activities. After we found that periostin is a downstream molecule of interleukin (IL)-4 and IL-13, signature cytokines of type 2 immune responses, we showed that periostin is a component of subepithelial fibrosis in bronchial asthma, the first formal proof that periostin is involved in allergic inflammation. Subsequently, a great deal of evidence has accumulated demonstrating the significance of periostin in allergic inflammation. It is of note that in skin tissues, periostin is critical for amplification and persistence of allergic inflammation by communicating between fibroblasts and keratinocytes. Furthermore, periostin has been applied to development of novel diagnostics or therapeutic agents for allergic diseases. Serum periostin can reflect local production of periostin in inflamed lesions induced by Th2-type immune responses and also can predict the efficacy of Th2 antagonists against bronchial asthma. Blocking the interaction between periostin and its receptor, αv integrin, or down-regulating the periostin expression shows improvement of periostin-induced inflammation in mouse models or in in vitro systems. It is hoped that diagnostics or therapeutic agents targeting periostin will be of practical use in the near future.

  18. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma.

    PubMed

    Caceres, Ana I; Brackmann, Marian; Elia, Maxwell D; Bessac, Bret F; del Camino, Donato; D'Amours, Marc; Witek, JoAnn S; Fanger, Chistopher M; Chong, Jayhong A; Hayward, Neil J; Homer, Robert J; Cohn, Lauren; Huang, Xiaozhu; Moran, Magdalene M; Jordt, Sven-Eric

    2009-06-01

    Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1(-/-) mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions. PMID:19458046

  19. Effects of exercise training on atrophy gene expression in skeletal muscle of mice with chronic allergic lung inflammation.

    PubMed

    Durigan, J L Q; Peviani, S M; Russo, T L; Silva, A C D; Vieira, R P; Martins, M A; Carvalho, C R F; Salvini, T F

    2009-04-01

    We evaluated the effects of chronic allergic airway inflammation and of treadmill training (12 weeks) of low and moderate intensity on muscle fiber cross-sectional area and mRNA levels of atrogin-1 and MuRF1 in the mouse tibialis anterior muscle. Six 4-month-old male BALB/c mice (28.5 +/- 0.8 g) per group were examined: 1) control, non-sensitized and non-trained (C); 2) ovalbumin sensitized (OA, 20 microg per mouse); 3) non-sensitized and trained at 50% maximum speed _ low intensity (PT50%); 4) non-sensitized and trained at 75% maximum speed _ moderate intensity (PT75%); 5) OA-sensitized and trained at 50% (OA+PT50%), 6) OA-sensitized and trained at 75% (OA+PT75%). There was no difference in muscle fiber cross-sectional area among groups and no difference in atrogin-1 and MuRF1 expression between C and OA groups. All exercised groups showed significantly decreased expression of atrogin-1 compared to C (1.01 +/- 0.2-fold): PT50% = 0.71 +/- 0.12-fold; OA+PT50% = 0.74 +/- 0.03-fold; PT75% = 0.71 +/- 0.09-fold; OA+PT75% = 0.74 +/- 0.09-fold. Similarly significant results were obtained regarding MuRF1 gene expression compared to C (1.01 +/- 0.23-fold): PT50% = 0.53 +/- 0.20-fold; OA+PT50% = 0.55 +/- 0.11-fold; PT75% = 0.35 +/- 0.15-fold; OA+PT75% = 0.37 +/- 0.08-fold. A short period of OA did not induce skeletal muscle atrophy in the mouse tibialis anterior muscle and aerobic training at low and moderate intensity negatively regulates the atrophy pathway in skeletal muscle of healthy mice or mice with allergic lung inflammation.

  20. Actual therapeutic management of allergic and hyperreactive nasal disorders

    PubMed Central

    Rudack, Claudia

    2004-01-01

    Allergic rhinitis (AR) and hyperractive disorders of the upper airways, depending upon the type of releasing stimuli, are defined as nasal hyperreactivity, for example in the case of AR, or as non-specific nasal hyperreactivity and as idiopathic rhinitis (IR) (synonyms frequently used in the past: non-specific nasal hyperreactivity; vasomotor rhinitis) in the case of non-characterised stimuli. An early and professional therapy of allergic disorders of the upper airways is of immense importance as allergic rhinitis is detected in comorbidities such as asthma and rhino sinusitis. The therapeutic concept is influenced by new and further developments in pharmacological substance classes such as antihistamines and glucocorticosteroids. Specific immune therapy, the only causal therapy for AR, has been reviewed over the past few years in respect of the type and pattern of application. However, to date no firm recommendations on oral, sublingual and /or nasal immune therapy have yet been drawn up based on investigations of these modifications. Therapeutic management of IR is aimed at a symptom-oriented therapy of nasal hyperactivity as etiological factors relating to this form of rhinitis are not yet sufficiently known. Drug groups such as mast cell stabilizers, systemic and topic antihistamines, topic and systemic glucocorticosteroids, ipatroium bromide and alpha symphatomimetics belong to the spectrum of the therapeutics employed. PMID:22073046

  1. The transcription factor PU.1 promotes alternative macrophage polarization and asthmatic airway inflammation.

    PubMed

    Qian, Feng; Deng, Jing; Lee, Yong Gyu; Zhu, Jimmy; Karpurapu, Manjula; Chung, Sangwoon; Zheng, Jun-Nian; Xiao, Lei; Park, Gye Young; Christman, John W

    2015-12-01

    The transcription factor PU.1 is involved in regulation of macrophage differentiation and maturation. However, the role of PU.1 in alternatively activated macrophage (AAM) and asthmatic inflammation has yet been investigated. Here we report that PU.1 serves as a critical regulator of AAM polarization and promotes the pathological progress of asthmatic airway inflammation. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, conditional PU.1-deficient (PU/ER(T)(+/-)) mice displayed attenuated allergic airway inflammation, including decreased alveolar eosinophil infiltration and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. The reduced asthmatic inflammation in PU/ER(T)(+/-) mice was restored by adoptive transfer of IL-4-induced wild-type (WT) macrophages. Moreover, after treating PU/ER(T)(+/-) mice with tamoxifen to rescue PU.1 function, the allergic asthmatic inflammation was significantly restored. In vitro studies demonstrate that treatment of PU.1-deficient macrophages with IL-4 attenuated the expression of chitinase 3-like 3 (Ym-1) and resistin-like molecule alpha 1 (Fizz-1), two specific markers of AAM polarization. In addition, PU.1 expression in macrophages was inducible in response to IL-4 challenge, which was associated with phosphorylation of signal transducer and activator of transcription 6 (STAT6). Furthermore, DRA challenge in sensitized mice almost abrogated gene expression of Ym-1 and Fizz-1 in lung tissues of PU/ER(T)(+/-) mice compared with WT mice. These data, all together, indicate that PU.1 plays a critical role in AAM polarization and asthmatic inflammation.

  2. [Allergic and irritative textile dermatitis].

    PubMed

    Elsner, P

    1994-01-22

    Textile dermatitis is only one example of adverse health effects due to clothing. It may present with a wide spectrum of clinical features, but the main mechanisms are irritant dermatitis, often observed in atopics intolerant to wool and synthetic fibers, and allergic contact dermatitis, usually caused by textile finishes and dyes. The newer azo dyes Disperse Blue 106 and 124 in particular are potent sensitizers that have caused significant problems, most recently in the form of "leggins dermatitis". Although severe textile dermatitis appears to be a rare event, more systematic population-based research is needed since many oligosymptomatic cases are probably overlooked. Criteria for healthy textiles are an optimum combination of efficacy (regulation of skin temperature and humidity and protection from environmental damage) and safety (lack of carcinogenicity, toxicity and allergenicity). If potentially allergenic substances are used in textiles, they should be declared as in the case of cosmetics.

  3. Sensitization by subcutaneous route is superior to intraperitoneal route in induction of asthma by house dust mite in a murine mode

    PubMed Central

    Aun, Marcelo Vivolo; Saraiva-Romanholo, Beatriz Mangueira; de Almeida, Francine Maria; Brüggemann, Thayse Regina; Kalil, Jorge; Martins, Milton de Arruda; Arantes-Costa, Fernanda Magalhães; Giavina-Bianchi, Pedro

    2015-01-01

    ABSTRACT Objective To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. Methods The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Results Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50mcg through subcutaneously route showed significant airway remodeling. Conclusion In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies. PMID:26761554

  4. Study of Allergic Rhinitis in Childhood

    PubMed Central

    Balatsouras, Dimitrios G.; Koukoutsis, George; Ganelis, Panayotis; Fassolis, Alexandros; Korres, George S.; Kaberos, Antonis

    2011-01-01

    Allergic rhinitis is common among children and quite often represents a stage of the atopic march. Although sensitization to food and airborne allergens may appear in infancy and early childhood, symptoms of the disease are usually present after age 3. The aim of this study was to determine the most frequent food and indoor and outdoor respiratory allergens involved in allergic rhinitis in children in the region of Piraeus. The study was performed in the outpatient clinic of otolaryngologic allergy of a general hospital. Fifty children (ranged 6–14 ) with symptoms of allergic rhinitis and positive radioallergosorbent test (RAST) for IgE antibodies or skin prick tests were included in the study. Thirty six (72%) of the subjects of the study had intermittent allergic rhinitis. The most common aeroallergens determined were grass pollens and Parietaria, whereas egg and milk were the food allergens identified. The detection of indoor and outdoor allergens in the region of Piraeus, based on skin prick tests and RAST tests, showed high incidence of grasses and food allergens, which is similar to other Mediterranean countries. PMID:21760801

  5. Cyclic nitroxide radicals attenuate inflammation and Hyper-responsiveness in a mouse model of allergic asthma.

    PubMed

    Assayag, Miri; Goldstein, Sara; Samuni, Amram; Berkman, Neville

    2015-10-01

    The effects of stable cyclic nitroxide radicals have been extensively investigated both in vivo and in vitro demonstrating anti-inflammatory, radioprotective, anti-mutagenic, age-retardant, hypotensive, anti-cancer and anti-teratogenic activities. Yet, these stable radicals have not been evaluated in asthma and other airway inflammatory disorders. The present study investigated the effect of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (TPL) and 3-carbamoyl-proxyl (3-CP) in a mouse model of ovalbumin (OVA)-induced allergic asthma. Both 3-CP and TPL were non-toxic when administered either orally (1% w/w nitroxide-containing chow) or via intraperitoneal (IP) injection (∼300 mg/kg). Feeding the mice orally demonstrated that 3-CP was more effective than TPL in reducing inflammatory cell recruitment into the airway and in suppressing airway hyper-responsiveness (AHR) in OVA-challenged mice. To characterize the optimal time-window of intervention and mode of drug administration, 3-CP was given orally during allergen sensitization, during allergen challenge or during both sensitization and challenge stages, and via IP injection or intranasal instillation for 3 days during the challenge period. 3-CP given via all modes of delivery markedly inhibited OVA-induced airway inflammation, expression of cytokines, AHR and protein nitration of the lung tissue. Oral administration during the entire experiment was the most efficient delivery of 3-CP and was more effective than dexamethasone a potent corticosteroid used for asthma treatment. Under a similar administration regimen (IP injection before the OVA challenge), the effect of 3-CP was similar to that of dexamethasone and even greater on AHR and protein nitration. The protective effect of the nitroxides, which preferentially react with free radicals, in suppressing the increase of main asthmatic inflammatory markers substantiate the key role played by reactive oxygen and nitrogen species in the molecular mechanism of

  6. Gut Microbiota and Allergic Disease. New Insights.

    PubMed

    Lynch, Susan V

    2016-03-01

    The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy. PMID:27027953

  7. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

    Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

    2011-01-01

    Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

  8. Leukemia inhibitory factor in the neuroimmune communication pathways in allergic asthma.

    PubMed

    Lin, Min-Juan; Lao, Xue-Jun; Liu, Sheng-Ming; Xu, Zhen-Hua; Zou, Wei-Feng

    2014-03-20

    In the pathogenesis of asthma, central sensitization is suggested to be an important neural mechanism, and neurotrophins and cytokines are likely to be the major mediators in the neuroimmune communication pathways of asthma. However, their impact on the central nervous system in allergic asthma remains unclear. We hypothesize that central neurogenic inflammation develops in the pathogenesis of allergic asthma, and nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are important mediators in its development. An asthma model of rats was established by sensitization and challenged with ovalbumin (OVA). For further confirmation of the role of LIF in neurogenic inflammation, a subgroup was pretreated with intraperitoneally (i.p.) LIF antibody before OVA challenge. The levels of LIF and NGF were measured with reverse transcription and polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry stain in lung tissue, airway-specific dorsal root ganglia (DRG, C7-T5) and brain stem of asthmatic rats, anti-LIF pretreated rats and controls. A significantly increased number of LIF- and NGF-immunoreactive cells were detected in lung tissue, DRG and the brain stem of asthmatic rats. In the asthma group a significantly increase level of mRNA encoding LIF and NGF in lung tissue was detected, but not in DRG and the brain stem. Pretreatment with LIF antibody decreased the level of LIF and NGF in all tissues. LIF is an important mediator in the crosstalk between nerve and immune systems. Our study demonstrate that the increased level of LIF and NGF in DRG and brain stem may be not based on result from de novo synthesis, but rather on result from retrograde nerve transport or passage across the blood-brain-barrier.

  9. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    PubMed Central

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    Background Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though

  10. Th2 Allergic Immune Response to Inhaled Fungal Antigens is Modulated By TLR-4-Independent Bacterial Products

    PubMed Central

    Allard, Jenna B.; Rinaldi, Lisa; Wargo, Matt; Allen, Gilman; Akira, Shizuo; Uematsu, Satoshi; Poynter, Matthew E.; Hogan, Deborah A.; Rincon, Mercedes; Whittaker, Laurie A.

    2009-01-01

    SUMMARY Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well know triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4-independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response, and potentially impact the development of allergic airway disease to environmental fungal antigens. PMID:19224641

  11. The emergency airway.

    PubMed

    Goon, Serena S H; Stephens, Robert C M; Smith, Helen

    2009-12-01

    The 'can't intubate, can't ventilate' scenario is a nightmare for all clinicians who manage airways. Cricothyroidotomy is one of several emergency airway management techniques. Cricothyroidotomy is a short-term solution which provides oxygenation, not ventilation, and is not a definitive airway. Although there are tests which can help predict whether an intubation will be difficult, they are not always good predictors. As the can't intubate, can't ventilate scenario is rare, cricothyroidotomy is an unfamiliar procedure to many. In this situation, expert help must be called for early on. In the meantime, it is vital that all other simple airway manoeuvres have been attempted, such as good positioning of the patient with head tilt and chin lift, and use of airway adjuncts like the oral (Guedel) airway or nasopharyngeal airway, and the laryngeal mask airway. However, if attempts to secure the airway are unsuccessful, there may be no other option than to perform a cricothyroidotomy. It is a difficult decision to make, but with increasing hypoxia, it is essential that one oxygenates the patient. Cricothyroidotomy provides an opening in the pace between the anterior inferior border of the thyroid cartilage and the anterior superior border of the cricoid cartilage, allowing access to the airway below the glottis. The anatomical considerations are important when performing this procedure (Ellis, 2009), and there are other scenarios when it is used. It is not without consequence, as with any procedure.

  12. Airway hyperreactivity elicited by toluene diisocyanate (TDI)-albumin conjugate is not accompanied by airway eosinophilic infiltration in guinea pigs.

    PubMed

    Huang, J; Millecchia, L L; Frazer, D G; Fedan, J S

    1998-02-01

    Nonspecific airway hyperresponsiveness is present in many patients with toluene diisocyanate (TDI)-induced asthma; however, the underlying pathophysiological mechanisms of this hyperresponsiveness remain controversial. In the present study, we used a guinea pig model to investigate the association of TDI-induced airway hyperresponsiveness with eosinophilic airway infiltration, which is widely considered to play a key role in the development of allergen-induced hyperresponsiveness. Guinea pigs were sensitized by i.d. injections of 10 microl TDI on day 1 and day 6. Control animals received saline injections. Two weeks after the second injection, airway reactivity to inhaled methacholine and specific airway resistance (sRaw) was measured before and at several times after inhalation challenge with TDI-GSA (guinea pig serum albumin) conjugates. Eosinophils in the airways were detected using enzyme histochemistry and quantified using computer-assisted image analysis. TDI-specific IgG1 antibodies were found in the blood of TDI-sensitized animals. An immediate increase in sRaw was induced in these animals by TDI-GSA challenge; airway hyperresponsiveness to methacholine was observed at 6 h and 18 h after TDI-GSA challenge. However, TDI-GSA challenge did not result in an elevation of eosinophils in the airways, compared with control animals. The results suggest that the development of TDI-induced airway hyperresponsiveness is not dependent upon eosinophil infiltration in airways. PMID:9520137

  13. Shoe allergic contact dermatitis.

    PubMed

    Matthys, Erin; Zahir, Amir; Ehrlich, Alison

    2014-01-01

    Foot dermatitis is a widespread condition, affecting men and women of all ages. Because of the location, this condition may present as a debilitating problem to those who have it. Allergic contact dermatitis involving the feet is frequently due to shoes or socks. The allergens that cause shoe dermatitis can be found in any constituent of footwear, including rubber, adhesives, leather, dyes, metals, and medicaments. The goal of treatment is to identify and minimize contact with the offending allergen(s). The lack of product information released from shoe manufacturers and the continually changing trends in footwear present a challenge in treating this condition. The aim of this study is to review the current literature on allergic contact shoe dermatitis; clinical presentation, allergens, patch testing, and management will be discussed. PubMed and MEDLINE databases were used for the search, with a focus on literature updates from the last 15 years.

  14. Antileukotrienes in upper airway inflammatory diseases.

    PubMed

    Cingi, Cemal; Muluk, Nuray Bayar; Ipci, Kagan; Şahin, Ethem

    2015-11-01

    Leukotrienes (LTs) are a family of inflammatory mediators including LTA4, LTB4, LTC4, LTD4, and LTE4. By competitive binding to the cysteinyl LT1 (CysLT1) receptor, LT receptor antagonist drugs, such as montelukast, zafirlukast, and pranlukast, block the effects of CysLTs, improving the symptoms of some chronic respiratory diseases, particularly bronchial asthma and allergic rhinitis. We reviewed the efficacy of antileukotrienes in upper airway inflammatory diseases. An update on the use of antileukotrienes in upper airway diseases in children and adults is presented with a detailed literature survey. Data on LTs, antileukotrienes, and antileukotrienes in chronic rhinosinusitis and nasal polyps, asthma, and allergic rhinitis are presented. Antileukotriene drugs are classified into two groups: CysLT receptor antagonists (zafirlukast, pranlukast, and montelukast) and LT synthesis inhibitors (5-lipoxygenase inhibitors such as zileuton, ZD2138, Bay X 1005, and MK-0591). CysLTs have important proinflammatory and profibrotic effects that contribute to the extensive hyperplastic rhinosinusitis and nasal polyposis (NP) that characterise these disorders. Patients who receive zafirlukast or zileuton tend to show objective improvements in, or at least stabilisation of, NP. Montelukast treatment may lead to clinical subjective improvement in NP. Montelukast treatment after sinus surgery can lead to a significant reduction in eosinophilic cationic protein levels in serum, with a beneficial effect on nasal and pulmonary symptoms and less impact in NP. Combined inhaled corticosteroids and long-acting β-agonists treatments are most effective for preventing exacerbations among paediatric asthma patients. Treatments with medium- or high-dose inhaled corticosteroids, combined inhaled corticosteroids and LT receptor antagonists, and low-dose inhaled corticosteroids have been reported to be equally effective. Antileukotrienes have also been reported to be effective for allergic

  15. [Pseudotumoral allergic bronchopulmonary aspergillosis].

    PubMed

    Otero González, I; Montero Martínez, C; Blanco Aparicio, M; Valiño López, P; Verea Hernando, H

    2000-06-01

    Allergic bronchopulmonary aspergillosis (ABPA) develops as the result of a hypersensitivity reaction to fungi of the genus Aspergillus. Clinical and radiological presentation can be atypical, requiring a high degree of suspicion on the part of the physician who treats such patients. We report the cases of two patients with APBA in whom the form of presentation--with few asthma symptoms, images showing lobar atelectasia and hilar adenopathy--led to an initial suspicion of lung cancer. PMID:10932345

  16. Long-lived Th2 memory in experimental allergic asthma.

    PubMed

    Mojtabavi, Nazanin; Dekan, Gerhard; Stingl, Georg; Epstein, Michelle M

    2002-11-01

    Although life-long immunity against pathogens is beneficial, immunological memory responses directed against allergens are potentially harmful. Because there is a paucity of information about Th2 memory cells in allergic disease, we established a model of allergic asthma in BALB/c mice to explore the generation and maintenance of Th2 memory. We induced disease without the use of adjuvants, thus avoiding Ag depots, and found that unlike allergic asthma in mice immunized with adjuvant, immunizing with soluble and aerosol OVA resulted in pathological lung lesions resembling human disease. To test memory responses we allowed mice with acute disease to recover and then re-exposed them to aerosol OVA a second time. Over 400 days later these mice developed OVA-dependent eosinophilic lung inflammation, airway hyperresponsiveness, mucus hypersecretion, and IgE. Over 1 year after recuperating from acute disease, mice had persistent lymphocytic lung infiltrates, Ag-specific production of IL-4 and IL-5 from spleen and lung cells in vitro, and elevated IgG1. Moreover, when recuperated mice were briefly aerosol challenged, we detected early expression of Th2 cytokine RNA in lungs. Taken together, these data demonstrate the presence of long-lived Th2 memory cells in spleen and lungs involved in the generation of allergic asthma upon Ag re-exposure.

  17. Ambient air pollution and allergic diseases in children.

    PubMed

    Kim, Byoung-Ju; Hong, Soo-Jong

    2012-06-01

    The prevalence of allergic diseases has increased worldwide, a phenomenon that can be largely attributed to environmental effects. Among environmental factors, air pollution due to traffic is thought to be a major threat to childhood health. Residing near busy roadways is associated with increased asthma hospitalization, decreased lung function, and increased prevalence and severity of wheezing and allergic rhinitis. Recently, prospective cohort studies using more accurate measurements of individual exposure to air pollution have been conducted and have provided definitive evidence of the impact of air pollution on allergic diseases. Particulate matter and ground-level ozone are the most frequent air pollutants that cause harmful effects, and the mechanisms underlying these effects may be related to oxidative stress. The reactive oxidative species produced in response to air pollutants can overwhelm the redox system and damage the cell wall, lipids, proteins, and DNA, leading to airway inflammation and hyper-reactivity. Pollutants may also cause harmful effects via epigenetic mechanisms, which control the expression of genes without changing the DNA sequence itself. These mechanisms are likely to be a target for the prevention of allergies. Further studies are necessary to identify children at risk and understand how these mechanisms regulate gene-environment interactions. This review provides an update of the current understanding on the impact of air pollution on allergic diseases in children and facilitates the integration of issues regarding air pollution and allergies into pediatric practices, with the goal of improving pediatric health.

  18. Local IgE in non-allergic rhinitis.

    PubMed

    Campo, P; Rondón, C; Gould, H J; Barrionuevo, E; Gevaert, P; Blanca, M

    2015-05-01

    Local allergic rhinitis (LAR) is characterized by the presence of a nasal Th2 inflammatory response with local production of specific IgE antibodies and a positive response to a nasal allergen provocation test (NAPT) without evidence of systemic atopy. The prevalence has been shown to be up to 25% in subjects affected with rhinitis with persistence, comorbidity and evolution similar to allergic rhinitis. LAR is a consistent entity that does not evolve to allergic rhinitis with systemic atopy over time although patients have significant impairment in quality of life and increase in the severity of nasal symptoms over time. Lower airways can be also involved. The diagnosis of LAR is based mostly on demonstration of positive response to NAPT and/or local synthesis of specific IgE. Allergens involved include seasonal or perennial such as house dusts mites, pollens, animal epithelia, moulds (alternaria) and others. Basophils from peripheral blood may be activated by the involved allergens suggesting the spill over of locally synthesized specific IgE to the circulation. LAR patients will benefit from the same treatment as allergic patients using antihistamines, inhaled corticosteroids and IgE antagonists. Studies on immunotherapy are ongoing and will determine its efficacy in LAR in terms of symptoms improvement and evolution of the natural course of the disease.

  19. Management of allergic rhinitis

    PubMed Central

    Solelhac, Geoffroy

    2014-01-01

    In this paper, we review the current management of allergic rhinitis and new directions for future treatment. Currently, management includes pharmacotherapy, allergen avoidance and possibly immunotherapy. The simple washing of nasal cavities using isotonic saline provides a significant improvement and is useful, particularly in children. The most effective medication in persistent rhinitis used singly is topical corticosteroid, which decreases all symptoms, including ocular ones. Antihistamines reduce nasal itch, sneeze and rhinorrhea and can be used orally or topically. When intranasal antihistamine is used together with topical corticosteroid, the combination is more effective and acts more rapidly than either drug used alone. Alternative therapies, such as homeopathy, acupuncture and intranasal carbon dioxide, or devices such nasal air filters or intranasal cellulose, have produced some positive results in small trials but are not recommended by Allergic Rhinitis and its Impact on Asthma (ARIA). In the field of allergic immunotherapy, subcutaneous and sublingual routes are currently used, the former being perhaps more efficient and the latter safer. Sublingual tablets are now available. Their efficacy compared to standard routes needs to be evaluated. Efforts have been made to develop more effective and simpler immunotherapy by modifying allergens and developing alternative routes. Standard allergen avoidance procedures used alone do not provide positive results. A comprehensive, multi-trigger, multi-component approach is needed, including avoidance of pollutants such as cigarette smoke. PMID:25374672

  20. Small airways function of silica-exposed workers.

    PubMed

    Chia, K S; Ng, T P; Jeyaratnam, J

    1992-01-01

    Small airways obstruction may be present for many years before chronic airway obstruction becomes evident. Several spirometric indices, especially flow rates at low lung volumes, may reflect the status of small airways. Time domain indices, by using moments analysis of the volume time spirogram, have also been shown to be sensitive indicators of small airways obstruction. In this study, we have applied the various spirometric indices as well as time domain indices to a group of granite quarry workers without radiographic evidence of silicosis or physiological evidence of obstruction to the larger airways. The aim was to evaluate small airways function in relation to dust exposure in subjects with normal ratio of the forced expiratory volume in one second to the forced vital capacity (FEV1/FVC) and normal FVC. The volume-time spirograms of 140 quarry workers were digitized using an electronic digitizer connected to a microcomputer where flow and time domain indices were computed. The workers were divided into three exposure groups based on their occupational history. With adjustment for age, height, and smoking status, all the time domain indices showed significant small airways obstruction with increasing dust exposure. Smokers had greater degree of airways obstruction than the non-smokers, with a similar trend of increase in small airways obstruction in relation to higher exposure. Our present study suggests that small airways obstruction is present among silica exposed workers in the absence of radiological evidence of silicosis and large airways obstruction. There was also evidence of increasing small airways obstruction in higher dust exposure group. Our study also suggests that time domain indices are more sensitive to small airways obstruction.

  1. Ozone-induced modulation of airway hyperresponsiveness in guinea pigs.

    PubMed

    Schlesinger, Richard B; Cohen, Mitchell; Gordon, Terry; Nadziejko, Christine; Zelikoff, Judith T; Sisco, Maureen; Regal, Jean F; Ménache, Margaret G

    2002-06-01

    Although acute exposure to ozone (03*) has been shown to influence the severity and prevalence of airway hyperresponsiveness, information has been lacking on effects due to long-term exposure at relatively low exposure concentrations. The goals of this study were to determine whether long-term repeated ozone exposures could induce nonspecific hyperresponsiveness in normal, nonatopic (nonsensitized) animals, whether such exposure could exacerbate the preexisting hyperresponsive state in atopic (sensitized) animals, or both. The study was also designed to determine whether gender modulated airway responsiveness related to ozone exposure. Airway responsiveness was measured during and after exposure to 0.1 and 0.3 ppm ozone for 4 hours/day, 4 days/week for 24 weeks in normal, nonsensitized guinea pigs, in guinea pigs sensitized to an allergen (ovalbumin) prior to initiation of ozone exposures, and in animals sensitized concurrently with ozone exposures. Both male and female animals were studied. Ozone exposure did not produce airway hyperresponsiveness in nonsensitized animals. Ozone exposure did exacerbate airway hyperresponsiveness to specific and nonspecific bronchoprovocation in both groups of sensitized animals, and this effect persisted at least 4 weeks after the end of the exposures. Although the overall degree of airway responsiveness did differ between genders (males had more responsive airways than did females), the airway response to ozone exposure did not differ between the two groups. Ozone-induced effects upon airway responsiveness were not asso