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Sample records for allergic skin response

  1. Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.

    PubMed

    Kimata, Hajime

    2003-11-01

    The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients. PMID:14637240

  2. A new, rapid in vivo method to evaluate allergic responses through distinctive distribution of a fluorescent-labeled immune complex: Potential to investigate anti-allergic effects of compounds administered either systemically or topically to the skin.

    PubMed

    Yamaki, Kouya; Yoshino, Shin

    2016-01-01

    We herein established a new method to evaluate allergic responses in mice rapidly and easily with ethical improvement by reducing the number of animals used. A single intravenous injection of a mixture of anti-OVA monoclonal IgE and fluorescein-ovalbumin (FITC-OVA) induced the distinctive spotted distribution of FITC-OVA in skin, named "ASDIS (Anaphylaxis-dependent Spotted Distribution of a fluorescent-labeled Immune complex in Skin)", and this was easily detected by in vivo imaging. The parallel induction of hypothermia, scratching, serum histamine increases, and ASDIS as well as the inhibition of ASDIS by either the systemic administration of a histamine H1 receptor antagonist or mast cell-depleting antibody suggested that our method, which only required 15 min, induced these allergic responses including ASDIS. Relatively mild but significant ASDIS was induced also in mice with passive systemic anaphylaxis by the method, requiring 2 separate days. The painting of anti-histamines on the skin markedly reduced ASDIS in the painted area only, suggesting the potential of this model to simultaneously compare the anti-allergic effects of several candidate compounds with control drugs in the same mice. ASDIS was suggested to originate from extravasated FITC-OVA/OE-1 immune complexes from blood to skin tissues other than mast cells. Our new method has the advantages of rapidity, easy method, and lower animal numbers to evaluate anti-allergic compounds as well as the characteristics of the used antibody, antigen, labeling molecules, additives, and other formulations. Our model for inducing ASDIS may contribute to the development of anti-allergic drugs, especially those intended for application to the skin. PMID:26643682

  3. 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.

  4. Listening to mozart reduces allergic skin wheal responses and in vitro allergen-specific IgE production in atopic dermatitis patients with latex allergy.

    PubMed

    Kimata, Hajime

    2003-01-01

    In atopic dermatitis patients with latex allergy, listening to Mozart reduced skin wheal responses induced by latex, but not by histamine, whereas listening to Beethoven failed to produce similar results. Listening to Mozart also decreased in vitro total IgE and latex-specific IgE production with concomitant skewing of the cytokine pattern toward the Th1 type, that is, an increase in Th1 cytokine production and decrease in Th2 cytokine production by peripheral blood mononuclear cells, whereas listening to Beethoven failed to do so. These results suggest that therapy using specific types of music may be an effective treatment of allergic diseases. PMID:14977243

  5. Skin Prick Test in Patients with Chronic Allergic Skin Disorders

    PubMed Central

    Bains, Pooja; Dogra, Alka

    2015-01-01

    Background: Chronic allergic skin disorders are the inflammatory and proliferative conditions in which both genetic and environmental factors play important roles. Chronic idiopathic urticaria (CIU) and atopic dermatitis (AD) are among the most common chronic allergic skin disorders. These can be provoked by various food and aeroallergens. Skin prick tests (SPTs) represent the cheapest and most effective method to diagnose type I hypersensitivity. Positive skin tests with a history suggestive of clinical sensitivity strongly incriminate the allergen as a contributor to the disease process. Aims and Objectives: To determine the incidence of positive SPT in patients with chronic allergic skin disorders and to identify the various allergens implicated in positive SPT. Methods: Fifty patients of chronic allergic disorders were recruited in this study. They were evaluated by SPT with both food and aeroallergens. Results: In our study, SPT positivity in patients of CIU was 63.41% and in AD was 77.78%. Out of the 41 patients of CIU, the most common allergen groups showing SPT positivity were dust and pollen, each comprising 26.83% patients. SPT reaction was positive with food items (21.6%), insects (17.07%), fungus (12.20%), and Dermatophagoides farinae, that is, house dust mite (HDM) (7.32%). The allergen which showed maximum positivity was grain dust wheat (19.51%). Among nine patients of AD, maximum SPT positivity was seen with Dermatophagoides farinae, pollen Amaranthus spinosus, grain dust wheat, and cotton mill dust; each comprising 22.22% of patients. Conclusion: Our study showed that a significant number of patients of CIU and AD showed sensitivity to dust, pollen, insects, Dermatophagoides farinae, and fungi on SPT. Thus, it is an important tool in the diagnosis of CIU and AD. PMID:25814704

  6. Astemizole, a potent histamine H1-receptor antagonist: effect in allergic rhinoconjunctivitis, on antigen and histamine induced skin weal responses and relationship to serum levels.

    PubMed

    Howarth, P H; Emanuel, M B; Holgate, S T

    1984-07-01

    The efficacy of astemizole, a new, long acting, oral histamine H1-receptor antagonist was compared to placebo for the treatment of allergic rhinitis and conjunctivitis during the grass pollen season of 1982. Sixty-three patients with a positive skin prick test to grass pollen and current symptoms participated in an 8 week, double-blind, randomized study. Astemizole, 10 mg, was significantly better than placebo in alleviating both nose (P less than 0.05) and eye (P less than 0.01) symptoms despite significantly greater use of the reserve medication, clemastine, by the placebo group (P less than 0.003). There was a lag period of 5 days after initiation of therapy before treatment benefit became manifest. Subdivision of nasal symptoms indicated significant improvement compared to placebo over the 8 weeks for sneezing (P less than 0.05) and runny nose (P less than 0.05) but not blocked nose. The absence of effect on nasal blockage was confirmed by parallel measurement of nasal calibre by body plethysmography. The antihistaminic potency of astemizole was indicated by an 80% inhibition of the histamine induced skin weal response after 8 weeks therapy. A positive correlation was found between serum drug levels and % inhibition of histamine skin weal (r = 0.64, P less than 0.001). Astemizole was free from adverse sedative or anticholinergic effects but did cause a mean increase in weight of 1.3 kg (P less than 0.01) after 8 weeks therapy, not found with placebo. PMID:6146346

  7. Enhancement of allergic skin wheal responses and in vitro allergen-specific IgE production by computer-induced stress in patients with atopic dermatitis.

    PubMed

    Kimata, Hajime

    2003-04-01

    Computer-induced stress enhanced allergen-specific skin wheal responses in patients with atopic dermatitis (AD) while it failed to do so in patients with allergic rhinitis (AR). Computer-induced stress also enhanced plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP) in patients with AD, but not with AR. Peripheral blood mononuclear cells stimulated with combination of IL-4, IL-10, anti-CD40 mAb, and allergen produced allergen-specific IgE production in both patients with AD and AR. Computer-induced stress enhanced allergen-specific IgE production by peripheral blood mononuclear cells from patients with AD, but not from patients with AR. This is the first report that computer-induced stress enhances allergen-specific responses with concomitant increase of plasma levels of SP and VIP specifically in patients with AD. Since AD is often aggravated by stress, these finding may have implications for the pathophysiology and treatment of AD. PMID:12676575

  8. Skin Testing for Allergic Rhinitis: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background Allergic rhinitis is the most common type of allergy worldwide. The accuracy of skin testing for allergic rhinitis is still debated. This health technology assessment had two objectives: to determine the diagnostic accuracy of skin-prick and intradermal testing in patients with suspected allergic rhinitis and to estimate the costs to the Ontario health system of skin testing for allergic rhinitis. Methods We searched All Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database for studies that evaluated the diagnostic accuracy of skin-prick and intradermal testing for allergic rhinitis using nasal provocation as the reference standard. For the clinical evidence review, data extraction and quality assessment were performed using the QUADAS-2 tool. We used the bivariate random-effects model for meta-analysis. For the economic evidence review, we assessed studies using a modified checklist developed by the (United Kingdom) National Institute for Health and Care Excellence. We estimated the annual cost of skin testing for allergic rhinitis in Ontario for 2015 to 2017 using provincial data on testing volumes and costs. Results We meta-analyzed seven studies with a total of 430 patients that assessed the accuracy of skin-prick testing. The pooled pair of sensitivity and specificity for skin-prick testing was 85% and 77%, respectively. We did not perform a meta-analysis for the diagnostic accuracy of intradermal testing due to the small number of studies (n = 4). Of these, two evaluated the accuracy of intradermal testing in confirming negative skin-prick testing results, with sensitivity ranging from 27% to 50% and specificity ranging from 60% to 100%. The other two studies evaluated the accuracy of intradermal testing as a stand-alone tool for diagnosing allergic rhinitis, with

  9. Skin testing for allergic diseases: techniques, indications and interpretations.

    PubMed

    Villacorte, G V

    1978-01-01

    Despite significant strides in serologic methodologies, the skin test, when properly done, has remained the single most sensitive and practical assay for specific dermal-bound reaginic antibody. Its value could further be enhanced if and when characterization and standardization of the allergen extracts become a reality. While the technique is simple, the indications and interpretations of allergy skin tests required the expertise of well-trained allergists. A positive skin reaction is no more than a mere supportive laboratory aid in the diagnosis of allergic disease, which is arrived at through a carefully taken detailed history and a meticulously done physical examination. PMID:748833

  10. NKp46 regulates allergic responses

    PubMed Central

    Ghadially, Hormas; Horani, Amjad; Glasner, Ariella; Elboim, Moran; Gazit, Roi; Shoseyov, David; Mandelboim, Ofer

    2013-01-01

    Natural killer (NK) cells are cytotoxic cells that are able to rapidly kill viruses, tumor cells, parasites, bacteria, and even cells considered “self”. The activity of NK cells is controlled by a fine balance of inhibitory and activating signals mediated by a complex set of different receptors. However, the function of NK cells is not restricted only to the killing of target cells, NK cells also possess other properties such as the secretion of proangiogenic factors during pregnancy. Here, we demonstrate another unique NK-cell activity, namely the regulation of T-cell mediated allergic responses, which is dependent on the NK-cell specific receptor NKp46 (Ncr1 in mice). Using mice in which the Ncr1 gene has been replaced with a green fluorescent protein, we demonstrate reduced delayed-type hypersensitivity and airway hypersensitivity. Interestingly, we show that this reduction in airway hypersensitivity is due to differences in the stimulation of T cells resulting in an altered cytokine profile. PMID:23878025

  11. NKp46 regulates allergic responses.

    PubMed

    Ghadially, Hormas; Horani, Amjad; Glasner, Ariella; Elboim, Moran; Gazit, Roi; Shoseyov, David; Mandelboim, Ofer

    2013-11-01

    Natural killer (NK) cells are cytotoxic cells that are able to rapidly kill viruses, tumor cells, parasites, bacteria, and even cells considered "self". The activity of NK cells is controlled by a fine balance of inhibitory and activating signals mediated by a complex set of different receptors. However, the function of NK cells is not restricted only to the killing of target cells, NK cells also possess other properties such as the secretion of proangiogenic factors during pregnancy. Here, we demonstrate another unique NK-cell activity, namely the regulation of T-cell mediated allergic responses, which is dependent on the NK-cell specific receptor NKp46 (Ncr1 in mice). Using mice in which the Ncr1 gene has been replaced with a green fluorescent protein, we demonstrate reduced delayed-type hypersensitivity and airway hypersensitivity. Interestingly, we show that this reduction in airway hypersensitivity is due to differences in the stimulation of T cells resulting in an altered cytokine profile. PMID:23878025

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

    PubMed

    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

    2009-01-01

    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

  13. Allergic skin test reactivity to marijuana in the Southwest.

    PubMed

    Freeman, G L

    1983-06-01

    In a general allergy consultation practice in Arizona and western New Mexico, 129 patients were tested for immediate hypersensitivity skin test reactivity to marijuana pollen and tobacco leaf, as well as to a battery of other antigens. In all, 90 patients were diagnosed as allergic (atopic) and, of these, 63 (70 percent) were found to be skin test reactive to marijuana pollen and 18 (20 percent) to tobacco leaf. The incidence of skin test reactivity to marijuana was not significantly different for persons living at low, middle or high elevations throughout the Southwest. Marijuana sensitivity occurred in patients who were, in general, also sensitive to a variety of other airborne plant pollens. There was no close correlation, however, between sensitivity to marijuana pollen and sensitivity to pollens from elm, mulberry, hop and stinging nettle, which are botanically related to marijuana. The data suggest that marijuana pollen may be a relatively common airborne pollen pollutant in the Southwest, allergic persons being sensitized through inhalation. If this is confirmed by further studies, then clinical investigation of marijuana hyposensitization (immunotherapy) may be warranted. This is in contrast to tobacco allergy for which simple avoidance is recommended. PMID:6613109

  14. Allergic Skin Test Reactivity to Marijuana in the Southwest

    PubMed Central

    Freeman, Geraldine L.

    1983-01-01

    In a general allergy consultation practice in Arizona and western New Mexico, 129 patients were tested for immediate hypersensitivity skin test reactivity to marijuana pollen and tobacco leaf, as well as to a battery of other antigens. In all, 90 patients were diagnosed as allergic (atopic) and, of these, 63 (70 percent) were found to be skin test reactive to marijuana pollen and 18 (20 percent) to tobacco leaf. The incidence of skin test reactivity to marijuana was not significantly different for persons living at low, middle or high elevations throughout the Southwest. Marijuana sensitivity occurred in patients who were, in general, also sensitive to a variety of other airborne plant pollens. There was no close correlation, however, between sensitivity to marijuana pollen and sensitivity to pollens from elm, mulberry, hop and stinging nettle, which are botanically related to marijuana. The data suggest that marijuana pollen may be a relatively common airborne pollen pollutant in the Southwest, allergic persons being sensitized through inhalation. If this is confirmed by further studies, then clinical investigation of marijuana hyposensitization (immunotherapy) may be warranted. This is in contrast to tobacco allergy for which simple avoidance is recommended. PMID:6613109

  15. Epidermal RAF prevents allergic skin disease

    PubMed Central

    Raguz, Josipa; Jeric, Ines; Niault, Theodora; Nowacka, Joanna Daniela; Kuzet, Sanya Eduarda; Rupp, Christian; Fischer, Irmgard; Biggi, Silvia; Borsello, Tiziana; Baccarini, Manuela

    2016-01-01

    The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis-restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation. Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling: BRAF promotes ERK activation, while RAF1 dims stress kinase activation. In vivo, JNK inhibition prevents disease onset, while MEK/ERK inhibition in mice lacking epidermal RAF1 phenocopies it. These results support a primary role of keratinocytes in the pathogenesis of atopic dermatitis, and the animals lacking BRAF and RAF1 in the epidermis represent a useful model for this disease. DOI: http://dx.doi.org/10.7554/eLife.14012.001 PMID:27431613

  16. Food and Natural Materials Target Mechanisms to Effectively Regulate Allergic Responses.

    PubMed

    Shin, Hee Soon; Shon, Dong-Hwa

    2015-01-01

    An immune hypersensitivity disorder called allergy is caused by diverse allergens entering the body via skin contact, injection, ingestion, and/or inhalation. These allergic responses may develop into allergic disorders, including inflammations such as atopic dermatitis, asthma, anaphylaxis, food allergies, and allergic rhinitis. Several drugs have been developed to treat these allergic disorders; however, long-term intake of these drugs could have adverse effects. As an alternative to these medicines, food and natural materials that ameliorate allergic disorder symptoms without producing any side effects can be consumed. Food and natural materials can effectively regulate successive allergic responses in an allergic chain-reaction mechanism in the following ways: [1] Inhibition of allergen permeation via paracellular diffusion into epithelial cells, [2] suppression of type 2 T-helper (Th) cell-related cytokine production by regulating Th1/Th2 balance, [3] inhibition of pathogenic effector CD4(+) T cell differentiation by inducing regulatory T cells (Treg), and [4] inhibition of degranulation in mast cells. The immunomodulatory effects of food and natural materials on each target mechanism were scientifically verified and shown to alleviate allergic disorder symptoms. Furthermore, consumption of certain food and natural materials such as fenugreek, skullcap, chitin/chitosan, and cheonggukjang as anti-allergics have merits such as safety (no adverse side effects), multiple suppressive effects (as a mixture would contain various components that are active against allergic responses), and ease of consumption when required. These merits and anti-allergic properties of food and natural materials help control various allergic disorders. PMID:26598817

  17. DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES TO PENICILLIUM CHRYSOGENUM

    EPA Science Inventory

    ABSTRACT
    Indoor mold has been associated with development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and its viable conidia can induce allergic responses in a mouse model of allergic penicilliosis. The hypothesis o...

  18. Skin: Major target organ of allergic reactions to small molecular weight compounds

    SciTech Connect

    Merk, Hans F. Baron, Jens M.; Neis, Mark M.; Obrigkeit, Daniela Hoeller; Karlberg, Ann-Therese

    2007-11-01

    Skin is a major target organ for allergic reactions to small molecular weight compounds. Drug allergic reactions may be life-threatening such as in the case of anaphylactic reactions or bullous drug reactions and occur in about 5% of all hospitalized patients. Allergic contact dermatitis has an enormous influence on the social life of the patient because it is the most frequent reason for occupational skin diseases and the treatment and prevention of this disease cost approximately Euro 3 billion per year in Germany. The different proposed pathophysiological pathways leading to a drug eruption are discussed in this paper. All major enzymes which are involved in the metabolism of xenobiotica were shown to be present in skin. Evidence supporting the role of metabolism in the development of drug allergy and allergic contact dermatitis is demonstrated in the example of sulphonamides and fragrances.

  19. Epidermal Neuromedin U Attenuates IgE-Mediated Allergic Skin Inflammation.

    PubMed

    Mizukawa, Yoshiko; Doi, Takaaki; Yamazaki, Yoshimi; Kudo, Akihiko; Shiohara, Tetsuo

    2016-01-01

    Although keratinocyte-derived neuropeptide neuromedin U (NMU) mediates the proinflammatory effects of innate-type mast cell activation, no information is available on the physiological roles. Here, to investigate the effects of NMU on IgE-mediated allergic skin inflammation, we determined whether IgE-mediated inflammation associated with severe scratching was induced in Nmu-/- mice administered repeated hapten applications to the ear or footpad. Dry skin was induced by targeted deletion of Nmu. Mice administered repeated hapten application developed IgE-mediated allergic inflammation characterized by severe scratching and increased serum IgE levels only when the ear, and not the footpad, was subjected to scratching, indicating that depletion of NMU from the epidermis alone does not drive such allergic inflammation. Thus, the susceptibility of Nmu-/- mice to allergic inflammation depends primarily on scratching dry skin. Further, allergic skin inflammation mediated by FcεRI cross-linking in Nmu-/-mice was inhibited by prior injection of NMU. These results indicate that NMU plays an important physiological role as a negative regulator during the late stage of IgE-mediated allergic skin inflammation. PMID:27463114

  20. Epidermal Neuromedin U Attenuates IgE-Mediated Allergic Skin Inflammation

    PubMed Central

    Mizukawa, Yoshiko; Doi, Takaaki; Yamazaki, Yoshimi; Kudo, Akihiko; Shiohara, Tetsuo

    2016-01-01

    Although keratinocyte-derived neuropeptide neuromedin U (NMU) mediates the proinflammatory effects of innate-type mast cell activation, no information is available on the physiological roles. Here, to investigate the effects of NMU on IgE-mediated allergic skin inflammation, we determined whether IgE-mediated inflammation associated with severe scratching was induced in Nmu-/- mice administered repeated hapten applications to the ear or footpad. Dry skin was induced by targeted deletion of Nmu. Mice administered repeated hapten application developed IgE-mediated allergic inflammation characterized by severe scratching and increased serum IgE levels only when the ear, and not the footpad, was subjected to scratching, indicating that depletion of NMU from the epidermis alone does not drive such allergic inflammation. Thus, the susceptibility of Nmu-/- mice to allergic inflammation depends primarily on scratching dry skin. Further, allergic skin inflammation mediated by FcεRI cross-linking in Nmu-/-mice was inhibited by prior injection of NMU. These results indicate that NMU plays an important physiological role as a negative regulator during the late stage of IgE-mediated allergic skin inflammation. PMID:27463114

  1. Emerging Antigens Involved in Allergic Responses

    PubMed Central

    Platts-Mills, Thomas A.E.; Commins, Scott P.

    2013-01-01

    New allergic diseases can “emerge” because of exposure to a novel antigen, because the immune responsiveness of the subject changes, or because of a change in the behavior of the population. Novel antigens have entered the environment as new pests in the home (e.g., Asian lady beetle or stink bugs), in the diet (e.g., prebiotics or wheat isolates), or because of the spread of a biting arthropod (e.g., ticks). Over the last few years, a significant new disease has been identified, which has changed the paradigm for food allergy. Bites of the tick, Amblyomma americanum, are capable of inducing IgE antibodies to galactose-alpha-1,3-galactose, which is associated with two novel forms of anaphylaxis. In a large area of the southeastern United States, the disease of delayed anaphylaxis to mammalian meat is now common. This disease challenges many previous rules about food allergy and provides a striking model of an emerging allergic disease. PMID:24095162

  2. 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

  3. Immune response phenotype of allergic versus clinically tolerant pigs in a neonatal swine model of allergy.

    PubMed

    Schmied, Julie; Rupa, Prithy; Garvie, Sarah; Wilkie, Bruce

    2013-07-15

    The prevalence of childhood food allergy and the duration of these allergies, particularly those considered to be transient, like egg and milk allergy, are increasing. The identification of allergic individuals using minimally invasive, non-anaphylaxis-threatening methods is therefore of increasing importance. In this experiment, correlates were sought of an allergic immune response (IR) phenotype in pigs. Using pigs pre-treated with heat-killed bacteria or bacterial components before allergic sensitization with the egg white protein ovomucoid (Ovm), differences were determined in IR phenotype of pigs in the categories treated-allergic, treated-tolerant, control-allergic (CA) and control-tolerant. Phenotype was established by measuring immunoglobulin (Ig)-associated antibody activity (AbA), cytokine profiles and the proportion of blood T-regulatory cells (T-regs) and observing late-phase allergen-specific skin tests (ST). Although 100% of pigs became sensitized to Ovm, only 33% of pigs had clinical signs of allergy after oral challenge with egg white. Pigs without clinical signs were classified as clinically tolerant. Sixty-seven percent of allergic pigs had a positive, late-phase ST classified as very strong or strong, while 84% of clinically tolerant pigs did not have late-phase ST. Treated-allergic pigs and CA pigs had greater total antibody IgG (H+L), IgE and IgG1 AbA than clinically tolerant pigs. Cytokine profiles of allergic pigs and the proportion of circulating T-regs, did not differ significantly between allergic and clinically tolerant pigs. Therefore, measurement of allergen-specific IgG, IgG1 and/or IgE activity and evaluation of late-phase ID ST may be useful in identifying allergic IR phenotypes in swine models of food allergy, which may be extended toward human use. PMID:23664639

  4. Staphylococcus δ-toxin promotes mouse allergic skin disease by inducing mast cell degranulation

    PubMed Central

    Nakamura, Yuumi; Oscherwitz, Jon; Cease, Kemp B.; Chan, Susana M.; Muñoz-Planillo, Raul; Hasegawa, Mizuho; Villaruz, Amer E.; Cheung, Gordon Y. C.; McGavin, Martin J.; Travers, Jeffrey B.; Otto, Michael; Inohara, Naohiro; Núñez, Gabriel

    2013-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15 to 30% of children and ~5% of adults in industrialized countries1. Although the pathogenesis of AD is not fully understood, the disease is mediated by an abnormal immunoglobulin E (IgE) immune response in the setting of skin barrier dysfunction2. Mast cells (MCs) contribute to IgE-mediated allergic disorders including AD3. Upon activation, MCs release their membrane-bound cytosolic granules leading to the release of multiple molecules that are important in the pathogenesis of AD and host defense4. More than 90% of AD patients are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbor the pathogen5. Several Staphylococcal exotoxins (SEs) can act as superantigens and/or antigens in models of AD6. However, the role of these SEs in disease pathogenesis remains unclear. Here, we report that culture supernatants of S. aureus contain potent MC degranulation activity. Biochemical analysis identified δ-toxin as the MC degranulation-inducing factor produced by S. aureus. MC degranulation induced by δ-toxin depended on phosphoinositide 3-kinase (PI3K) and calcium (Ca2+) influx, but unlike that mediated by IgE crosslinking, it did not require the spleen tyrosine kinase (Syk). In addition, IgE enhanced δ-toxin-induced MC degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from AD patients produced high levels of δ-toxin. Importantly, skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted IgE and IL-4 production, as well as inflammatory skin disease. Furthermore, enhancement of IgE production and dermatitis by δ-toxin was abrogated in KitW-sh/W-sh MC-deficient mice and restored by MC reconstitution. These studies identify δ-toxin as a potent inducer of MC degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease. PMID:24172897

  5. Skin Prick Test Analysis in Allergic Rhinitis Patients: A Preliminary Study in Abuja, Nigeria

    PubMed Central

    Ibekwe, T. S.

    2016-01-01

    Allergic rhinitis (AR) is prevalent in Nigeria, though little information exists on the allergen. We assessed the clinical features of AR patients in our environment based on the allergic rhinitis impact on asthma (ARIA) classification. Only patients with positive skin prick test (SPT) were recruited. Seventy-four patients participated in the study. AR and asthma comorbidity were observed in 13.5%. The proportion of “sneezers-runners” was higher than “blockers” with significantly more “sneezers-runners” having persistent AR (P = 0.007). No relationship was established between these predominant symptoms and the aeroallergens used in this study. Intermittent mild and moderate/severe AR were evident in 13.5% and 31.1%, while persistent mild and moderate/severe were seen in 20.3% and 35.1%, respectively. House dust mites allergen yielded the highest number of positive responses (22.6%) followed by tree pollen (16.8%). No relationship was observed between the allergens tested and AR severity. Majority of patients were oligosensitive (33.8%) and polysensitive (35.1%) and were not significantly associated with AR severity (P = 0.07). Most AR patients presenting for treatment in Abuja, Nigeria, had moderate-severe persistent AR and showed similar SPT sensitization pattern with countries having similar climatic conditions. Sensitization patterns were not related to ARIA classification or predominant AR symptoms. PMID:27247577

  6. Nerve growth factor partially recovers inflamed skin from stress-induced worsening in allergic inflammation.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Spatz, Katharina; Daniltchenko, Maria; Joachim, Ricarda; Gimenez-Rivera, Andrey; Hendrix, Sven; Botchkarev, Vladimir A; Brandner, Johanna M; Klapp, Burghard F

    2011-03-01

    Neuroimmune dysregulation characterizes atopic disease, but its nature and clinical impact remain ill-defined. Induced by stress, the neurotrophin nerve growth factor (NGF) may worsen cutaneous inflammation. We therefore studied the role of NGF in the cutaneous stress response in a mouse model for atopic dermatitis-like allergic dermatitis (AlD). Combining several methods, we found that stress increased cutaneous but not serum or hypothalamic NGF in telogen mice. Microarray analysis showed increased mRNAs of inflammatory and growth factors associated with NGF in the skin. In stress-worsened AlD, NGF-neutralizing antibodies markedly reduced epidermal thickening together with NGF, neurotrophin receptor (tyrosine kinase A and p75 neurotrophin receptor), and transforming growth factor-β expression by keratinocytes but did not alter transepidermal water loss. Moreover, NGF expression by mast cells was reduced; this corresponded to reduced cutaneous tumor necrosis factor-α (TNF-α) mRNA levels but not to changes in mast cell degranulation or in the T helper type 1 (Th1)/Th2 cytokine balance. Also, eosinophils expressed TNF receptor type 2, and we observed reduced eosinophil infiltration after treatment with NGF-neutralizing antibodies. We thus conclude that NGF acts as a local stress mediator in perceived stress and allergy and that increased NGF message contributes to worsening of cutaneous inflammation mainly by enhancing epidermal hyperplasia, pro-allergic cytokine induction, and allergy-characteristic cellular infiltration. PMID:21085186

  7. Maternal Influences over Offspring Allergic Responses

    PubMed Central

    2015-01-01

    Asthma occurs as a result of complex interactions of environmental and genetic factors. Clinical studies and animal models of asthma indicate offspring of allergic mothers have increased risk of development of allergies. Environmental factors including stress-induced corticosterone and vitamin E isoforms during pregnancy regulate the risk for offspring development of allergy. In this review, we discuss mechanisms for the development of allergic disease early in life, environmental factors that may impact the development of risk for allergic disease early in life, and how the variation in global prevalence of asthma may be explained, at least in part, by some environmental components. PMID:25612797

  8. Novel concept of iSALT (inducible skin-associated lymphoid tissue) in the elicitation of allergic contact dermatitis

    PubMed Central

    HONDA, Tetsuya; KABASHIMA, Kenji

    2016-01-01

    Allergic contact dermatitis (ACD) is one of the most common inflammatory skin diseases, which is classified as a delayed-type hypersensitivity immune response. The development of ACD is divided into two phases: sensitization and elicitation. In the sensitization phase, antigen-specific effector T cells are induced in the draining lymph nodes by antigen-captured cutaneous dendritic cells (DCs) that migrate from the skin. In the elicitation phase, the effector T cells are activated in the skin by antigen-captured cutaneous DCs and produce various chemical mediators, which create antigen-specific inflammation. In this review, we discuss the recent advancements in the immunological mechanisms of ACD, focusing on the mechanisms in the elicitation phase. The observations of elicitation of CHS lead to the emerging novel concept of iSALT (inducible skin-associated lymphoid tissue). PMID:26755397

  9. Preventative and Therapeutic Probiotic Use in Allergic Skin Conditions: Experimental and Clinical Findings

    PubMed Central

    Özdemir, Öner; Göksu Erol, Azize Yasemin

    2013-01-01

    Probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host. The interest in probiotic preventative/therapeutic potential in allergic diseases stemmed from the fact that probiotics have been shown to improve intestinal dysbiosis and permeability and to reduce inflammatory cytokines in human and murine experimental models. Enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against allergy. Therefore, many studies have been recently designed to examine the efficacy of probiotics, but the literature on the allergic skin disorders is still very scarce. Here, our objective is to summarize and evaluate the available knowledge from randomized or nonrandomized controlled trials of probiotic use in allergic skin conditions. Clinical improvement especially in IgE-sensitized eczema and experimental models such as atopic dermatitis-like lesions (trinitrochlorobenzene and picryl chloride sensitizations) and allergic contact dermatitis (dinitrofluorobenzene sensitization) has been reported. Although there is a very promising evidence to recommend the addition of probiotics into foods, probiotics do not have a proven role in the prevention or the therapy of allergic skin disorders. Thus, being aware of possible measures, such as probiotics use, to prevent/heal atopic diseases is essential for the practicing allergy specialist. PMID:24078929

  10. TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis

    PubMed Central

    Liu, Boyi; Escalera, Jasmine; Balakrishna, Shrilatha; Fan, Lu; Caceres, Ana I.; Robinson, Eve; Sui, Aiwei; McKay, M. Craig; McAlexander, M. Allen; Herrick, Christina A.; Jordt, Sven E.

    2013-01-01

    Allergic contact dermatitis is a common skin disease associated with inflammation and persistent pruritus. Transient receptor potential (TRP) ion channels in skin-innervating sensory neurons mediate acute inflammatory and pruritic responses following exogenous stimulation and may contribute to allergic responses. Genetic ablation or pharmacological inhibition of TRPA1, but not TRPV1, inhibited skin edema, keratinocyte hyperplasia, nerve growth, leukocyte infiltration, and antihistamine-resistant scratching behavior in mice exposed to the haptens, oxazolone and urushiol, the contact allergen of poison ivy. Hapten-challenged skin of TRPA1-deficient mice contained diminished levels of inflammatory cytokines, nerve growth factor, and endogenous pruritogens, such as substance P (SP) and serotonin. TRPA1-deficient sensory neurons were defective in SP signaling, and SP-induced scratching behavior was abolished in Trpa1−/− mice. SP receptor antagonists, such as aprepitant inhibited both hapten-induced cutaneous inflammation and scratching behavior. These findings support a central role for TRPA1 and SP in the integration of immune and neuronal mechanisms leading to chronic inflammatory responses and pruritus associated with contact dermatitis.—Liu, B., Escalera, J., Balakrishna, S., Fan, L., Caceres, A. I., Robinson, E., Sui, A., McKay, M. C., McAlexander, M. A., Herrick, C. A., Jordt, S. E. TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. PMID:23722916

  11. Oleanolic Acid Controls Allergic and Inflammatory Responses in Experimental Allergic Conjunctivitis

    PubMed Central

    Martínez-García, Carmen; Martín, Rubén; Gallego-Muñoz, Patricia; Hernández, Marita; Nieto, María L.

    2014-01-01

    Pollen is the most common aeroallergen to cause seasonal conjunctivitis. The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration. Oleanolic acid (OA) is natural a triterpene that displays strong anti-inflammatory and immunomodulatory properties being an active anti-allergic molecule on hypersensitivity reaction models. However, its effect on inflammatory ocular disorders including conjunctivits, has not yet been addressed. Hence, using a Ragweed pollen (RWP)-specific allergic conjunctivitis (EAC) mouse model we study here whether OA could modify responses associated to allergic processes. We found that OA treatment restricted mast cell degranulation and infiltration of eosinophils in conjunctival tissue and decreased allergen-specific Igs levels in EAC mice. Th2-type cytokines, secreted phospholipase A2 type-IIA (sPLA2-IIA), and chemokines levels were also significantly diminished in the conjunctiva and serum of OA-treated EAC mice. Moreover, OA treatment also suppressed RWP-specific T-cell proliferation. In vitro studies, on relevant cells of the allergic process, revealed that OA reduced the proliferative and migratory response, as well as the synthesis of proinflammatory mediators on EoL-1 eosinophils and RBL-2H3 mast cells exposed to allergic and/or crucial inflammatory stimuli such as RWP, sPLA2-IIA or eotaxin. Taken together, these findings demonstrate the beneficial activity of OA in ocular allergic processes and may provide a new intervention strategy and potential therapy for allergic diseases. PMID:24699261

  12. The Relationship between Skin Symptoms and Allergic Reactions to Asian Dust

    PubMed Central

    Otani, Shinji; Onishi, Kazunari; Mu, Haosheng; Yokoyama, Yae; Hosoda, Takenobu; Okamoto, Mikizo; Kurozawa, Youichi

    2012-01-01

    Asian dust events result from displacement of atmospheric pollutants from the Chinese and Mongolian deserts, causing associated health issues throughout Northeast Asia. We investigated the relationship between skin symptoms in Asian dust events and contact allergy to Asian dust and associated metals. Increases in atmospheric levels of heavy metals such as Ni, Al, and Fe occurred during the severe Asian dust event on March 21, 2010. We conducted a case–control study (n = 62) with patch testing to compare skin symptoms on an Asian dust day with metal allergic reactions. Skin symptoms were observed in 18/62 subjects. Nine subjects with skin symptoms (group A) and 11 without (group B) were patch tested for six metals and Asian dust particles. Metal and dust samples were applied to the subjects’ backs for 2 days and the reactions were scored according to the International Contact Dermatitis Research Group guidelines. Differences in the positive rates between the groups were analyzed. Skin reactions to ferric chloride (p = 0.015), aluminum chloride (p = 0.047), nickel sulfate (p = 0.008), and Asian dust particles (p = 0.047) were more common in group A than in group B. Skin symptoms during Asian dust events may be allergic reactions to Asian dust particle-bound metals. PMID:23222253

  13. Janus Kinase-3 Dependent Inflammatory Responses in Allergic Asthma

    PubMed Central

    Malaviya, Rama; Laskin, Debra L.; Malaviya, Ravi

    2010-01-01

    Summary Allergic asthma is a chronic inflammatory condition of the lung characterized by reversible airway obstruction, high serum immunoglobulin (Ig) E levels, and chronic airway inflammation. A number of cells including mast cells, T-cells, macrophages and dendritic cells play a role in the pathogenesis of the disease. Janus Kinase (JAK) −3, a nonreceptor protein tyrosine kinase, traditionally known to mediate cytokine signaling, also regulates functional responses of these cells. In this review the role of JAK-3 in regulating various pathogenic processes in allergic asthma is discussed. We propose that targeting JAK-3 is a rationale approach to control the inflammatory responses of multiple cell types responsible for the pathogenesis of allergic asthma. PMID:20430118

  14. Exposure to ambient bioaerosols is associated with allergic skin diseases in Greater Taipei residents.

    PubMed

    Kallawicha, Kraiwuth; Chuang, Ying-Chih; Lung, Shih-Chun Candice; Han, Bor-Cheng; Ting, Yi-Fang; Chao, Hsing Jasmine

    2016-09-01

    Allergic skin diseases may result from various types of chemical and biological allergens. This study investigated the association between ambient bioaerosol exposure and allergic skin diseases by using the exposure data obtained from land use regression models and interpolated data. Data on daily average outpatient visits for atopic dermatitis (ICD-9-CM 691.8) and contact dermatitis and other eczema (ICD-9-CM 692.9) between November 2011 and August 2012 were obtained from the National Health Insurance Research Database. A generalized estimating equation was used to analyze the associations between the skin diseases and ambient bioaerosol levels. The results indicated that during the study period, contact dermatitis and other eczema were more prevalent than atopic dermatitis in the study area. Most cases were observed in districts of Taipei City and 3 major districts of New Taipei City, namely Xinzhuang, Banqiao, and Xindian. In univariate analysis, most bioaerosols were positively associated with both skin diseases. After adjustment for air pollution and sociodemographic factors, exposure to total fungal spores was significantly associated with atopic dermatitis in males (relative risk [RR] = 1.12; 95% confidence interval [CI] = 1.05-1.19). Contact dermatitis and other eczema had significant relationships with Cladosporium in males (RR = 1.07; 95% CI = 1.02-1.14) and with Aspergillus/Penicillium in females (RR = 1.04; 95% CI = 1.02-1.07). Meteorological parameters, namely wind speed, temperature, and rainfall, were also significantly associated with skin diseases. Our findings reveal that exposure to ambient bioaerosols is a significant and independent risk factor for allergic skin diseases. PMID:27389548

  15. TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis.

    PubMed

    Liu, Boyi; Escalera, Jasmine; Balakrishna, Shrilatha; Fan, Lu; Caceres, Ana I; Robinson, Eve; Sui, Aiwei; McKay, M Craig; McAlexander, M Allen; Herrick, Christina A; Jordt, Sven E

    2013-09-01

    Allergic contact dermatitis is a common skin disease associated with inflammation and persistent pruritus. Transient receptor potential (TRP) ion channels in skin-innervating sensory neurons mediate acute inflammatory and pruritic responses following exogenous stimulation and may contribute to allergic responses. Genetic ablation or pharmacological inhibition of TRPA1, but not TRPV1, inhibited skin edema, keratinocyte hyperplasia, nerve growth, leukocyte infiltration, and antihistamine-resistant scratching behavior in mice exposed to the haptens, oxazolone and urushiol, the contact allergen of poison ivy. Hapten-challenged skin of TRPA1-deficient mice contained diminished levels of inflammatory cytokines, nerve growth factor, and endogenous pruritogens, such as substance P (SP) and serotonin. TRPA1-deficient sensory neurons were defective in SP signaling, and SP-induced scratching behavior was abolished in Trpa1(-/-) mice. SP receptor antagonists, such as aprepitant inhibited both hapten-induced cutaneous inflammation and scratching behavior. These findings support a central role for TRPA1 and SP in the integration of immune and neuronal mechanisms leading to chronic inflammatory responses and pruritus associated with contact dermatitis. PMID:23722916

  16. 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

  17. ASSESSMENT OF ALLERGIC IMMUNE RESPONSES TO INDOOR AIR FUNGAL CONTAMINANTS

    EPA Science Inventory

    We are using a mouse model to assess immune and inflammatory responses as well as changes in respiratory function and pathology characteristic of allergic asthma to fungal extracts M. anisopliae (MACA), S. chartarum (SCE), and P. chrysogenum (PCE). This model will be useful to a...

  18. 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

  19. Impact on allergic immune response after treatment with vitamin A

    PubMed Central

    Matheu, Victor; Berggård, Karin; Barrios, Yvelise; Barrios, Ysamar; Arnau, Maria-Rosa; Zubeldia, Jose M; Baeza, Maria L; Back, Ove; Issazadeh-Navikas, Shohreh

    2009-01-01

    Background Vitamin A may have some influence on the immune system, but the role in allergy modulation is still unclear. Objective To clarify whether high levels of retinoic acid (RA) affects allergic response in vivo, we used a murine experimental model of airway allergic disease. Methods Ovalbumin (OVA)-immunization/OVA-challenge (OVA/OVA) and house dust mite (HDM)-immunization/HDM-challenge (HDM/HDM) experimental murine models of allergic airway disease, using C57Bl.10/Q groups of mice (n = 10) treated subcutaneously with different concentrations of all-trans RA (0, 50, 500 and 2,500 ug) every 2-days were used to assess the allergic immune response. Results Levels of total and specific-IgE in sera were increased in all groups of RA treated OVA/OVA and HDM/HDM mice. Percentage and total amount of recruited eosinophil in airways by bronchoalveolar lavage fluid (BALF) were significantly enhanced in groups treated with 50, 500 and 2,500 ug of RA compared to non-treated mice. However, the group of mice treated with 2,500 ug had less eosinophil recruitment than the other two groups (50 and 500 ug). In parallel, levels of IL-5 and total IgE in BALF were also significantly diminished in the group treated with 2,500 ug compared to the other 2 groups (50 and 500 ug). Finally, total lung resistance was decreased in group treated with 2,500 ug compared to non-treated mice. Conclusion Our results suggest that retinoic acid directly enhances allergic response in vivo, but in higher doses may produce of immune suppression. PMID:19852821

  20. 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...

  1. Quercetin and Its Anti-Allergic Immune Response.

    PubMed

    Mlcek, Jiri; Jurikova, Tunde; Skrovankova, Sona; Sochor, Jiri

    2016-01-01

    Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase. PMID:27187333

  2. Induction of Allergic Responses to Peanut Allergen in Sheep

    PubMed Central

    Van Gramberg, Jenna L.; de Veer, Michael J.; O'Hehir, Robyn E.; Meeusen, Els N. T.; Bischof, Robert J.

    2012-01-01

    Peanut allergy is the leading cause of deaths due to food-induced anaphylaxis but despite continued research, there are currently no specific treatments available. Challenge testing is limited in patients due to the high risk of adverse reactions, emphasising the need for an appropriate animal model. In the present study we examine the induction of allergic responses in a sheep model for peanut allergy. Sheep were sensitised with peanut (PN) extract and in separate injections with ovalbumin (OVA) or house dust mite (HDM) extract. Serum PN-specific IgE responses were detected in 40–50% of immunised sheep, while only 10% (1 of 10 sheep) showed detectable OVA-specific IgE. All PN-allergic sheep tested showed an Ara h 1-specific IgE response, while four out of five allergic sheep showed an Ara h 2-specific IgE response. Animals with high serum IgE levels to HDM were also PN IgE-positive. Of the PN-sensitised animals with high PN-specific IgE, 80% also showed an immediate hypersensitivity reaction following an intradermal PN injection. This new large animal model of peanut allergy may provide a useful tool for future investigations of allergen-associated immune mechanisms and specific immunotherapy. PMID:23284686

  3. Contribution of endothelial selectins and alpha 4 integrins to eosinophil trafficking in allergic and nonallergic inflammatory reactions in skin.

    PubMed

    Teixeira, M M; Hellewell, P G

    1998-09-01

    The role of endothelial selectins in mediating eosinophil recruitment was assessed using the trafficking of 111In-labeled blood eosinophils in mouse skin. An intradermal injection of chemoattractants (leukotriene B4, macrophage inflammatory protein-l alpha, and eotaxin) resulted in a rapid accumulation of 111In eosinophils that was reduced 49 to 91% by anti-P-selectin mAb. An anti-E-selectin mAb was ineffective, although a combined E- and P-selectin blockade resulted in >95% inhibition of all responses. The accumulation of a pulse of 111In eosinophils at sites of active cutaneous anaphylaxis (ACA) at 4 to 8 h and at 20 to 24 h after Ag challenge was completely dependent upon E- and P-selectin in combination, but not in isolation. In contrast, at 20 to 24 h after Ag challenge in a delayed-type hypersensitivity (DTH) reaction in skin, 111In eosinophil accumulation was largely independent of endothelial selectins, even when L-selectin was also blocked. An anti-alpha 4 integrin mAb significantly reduced 111In eosinophil trafficking in both allergic reactions but was slightly more effective in the DTH reaction compared with the ACA reaction. These results show that P-selectin and to a lesser extent E-selectin mediate eosinophil recruitment in skin in acute inflammatory reactions. In allergic, late-onset inflammatory reactions, neither P- nor E-selectin alone are sufficient to mediate eosinophil accumulation; when combined, they are essential for trafficking in ACA but are less important in the DTH reaction. Whether alpha 4 integrin-based strategies will be more effective than selectin-based strategies at inhibiting eosinophil recruitment in human disease remains to be determined. PMID:9725251

  4. Cigarette Smoking and Skin Prick Test in Patients With Allergic Rhinitis

    PubMed Central

    Khazaei, Hossein Ali; Khazaei, Bahman; Dashtizadeh, Gholam Ali; Mohammadi, Mahdi

    2015-01-01

    Background: Allergic Rhinitis (AR) is the most common allergic disease, affecting 30% of population around the world. The disease is predominantly associated with exposure to some aeroallergens like cigarette smoking. Skin Prick Test (SPT) is a method of detecting immediate allergic reactions and is applied for controlling disease and therapeutic modality. Objectives: This study was designed to investigate the effect of cigarette smoking on SPT results among male and female individuals with AR disease. Patients and Methods: A total of 478 patients with AR admitted to the 2 main hospitals of Zahedan City from 2005 to 2012, were recruited in this analytic-descriptive study. Categories of smokers and never smokers were used based on patient’s statements and their history of smoking. SPT was performed with panel of some allergens and results were recorded and analyzed statistically. Odds ratio and confidence interval method were calculated using univariate logistic regression. Results: The results of this study indicated that 41.4% of patients with allergic rhinitis was smoker with ages ranged from 15 to 70 years. The result of this study also showed that smoking has no effect on SPT results of pollen and weeds aeroallergens conducted on male and female AR patients. However, male were significantly more sensitive than female in terms of sensitivity to the aspergillus, cladosporium, house dust mite, grasses, wheat, cockroach, and feather allergens. Conclusions: Our findings did not support the effect of cigarette smoking on SPT reactivity to pollen and weeds aeroallergens. However, male were significantly more sensitive than female in terms of sensitivity to some allergens. PMID:26495257

  5. Mast Cells Regulate Epidermal Barrier Function and the Development of Allergic Skin Inflammation.

    PubMed

    Sehra, Sarita; Serezani, Ana P M; Ocaña, Jesus A; Travers, Jeffrey B; Kaplan, Mark H

    2016-07-01

    Atopic dermatitis is a chronic inflammatory skin disease characterized by infiltration of eosinophils, T helper cells, and mast cells. The role of mast cells in atopic dermatitis is not completely understood. To define the effects of mast cells on skin biology, we observed that mast cells regulate the homeostatic expression of epidermal differentiation complex and other skin genes. Decreased epidermal differentiation complex gene expression in mice that genetically lack mast cells (Kit(W-sh/W-sh) mice) is associated with increased uptake of protein antigens painted on the skin by dendritic cells (DCs) compared with similarly treated wild-type mice, suggesting a protective role for mast cells in exposure to nominal environmental allergens. To test this further, we crossed Kit(W-sh/W-sh) mice with signal transducer and activator of transcription 6 (i.e., Stat6) VT transgenic mice that develop spontaneous atopic dermatitis-like disease that is dependent on T helper cell 2 cytokines and is associated with high serum concentrations of IgE. We observed that Stat6VT × Kit(W-sh/W-sh) mice developed more frequent and more severe allergic skin inflammation than Stat6VT transgenic mice that had mast cells. Together, these studies suggest that mast cells regulate epidermal barrier function and have a potential protective role in the development of atopic dermatitis-like disease. PMID:27021404

  6. DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BAL/C MICE

    EPA Science Inventory

    Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

  7. DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BALB/MICE

    EPA Science Inventory

    Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

  8. Role of Rho kinase isoforms in murine allergic airway responses.

    PubMed

    Zhu, M; Liu, P-Y; Kasahara, D I; Williams, A S; Verbout, N G; Halayko, A J; Fedulov, A; Shoji, T; Williams, E S; Noma, K; Shore, S A; Liao, J K

    2011-10-01

    Inhibition of Rho-associated coiled-coil forming kinases (ROCKs) reduces allergic airway responses in mice. The purpose of this study was to determine the roles of the two ROCK isoforms, ROCK1 and ROCK2, in these responses. Wildtype (WT) mice and heterozygous ROCK1 and ROCK2 knockout mice (ROCK1(+/-) and ROCK2(+/-), respectively) were sensitised and challenged with ovalbumin. ROCK expression and activation were assessed by western blotting. Airway responsiveness was measured by forced oscillation. Bronchoalveolar lavage was performed and the lungs were fixed for histological assessment. Compared with WT mice, ROCK1 and ROCK2 expression were 50% lower in lungs of ROCK1(+/-) and ROCK2(+/-) mice, respectively, without changes in the other isoform. In WT lungs, ROCK activation increased after ovalbumin challenge and was sustained for several hours. This activation was reduced in ROCK1(+/-) and ROCK2(+/-) lungs. Airway responsiveness was comparable in WT, ROCK1(+/-), and ROCK2(+/-) mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in WT, but not ROCK1(+/-) or ROCK2(+/-) mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1(+/-) and ROCK2(+/-) versus WT mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1(+/-) mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses. PMID:21565918

  9. 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

  10. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2014-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2013. Studies on food allergy suggest that (1) 7.6% of the US population is affected, (2) a "healthy" early diet might prevent food allergy, (3) the skin might be an important route of sensitization, (4) allergen component testing might aid diagnosis, (5) the prognosis of milk allergy might be predictable through early testing, (6) oral or sublingual immunotherapy show promise but also have caveats, and (7) preclinical studies show promising alternative modes of immunotherapy and desensitization. Studies on eosinophilic esophagitis show a relationship to connective tissue disorders and that dietary management is an effective treatment for adults. Markers of anaphylaxis severity have been determined and might inform potential diagnostics and therapeutic targets. Insights on serum tests for drug and insect sting allergy might result in improved diagnostics. Genetic and immune-mediated defects in skin epithelial differentiation contribute to the severity of atopic dermatitis. Novel management approaches to treatment of chronic urticaria, including use of omalizumab, are being identified. PMID:24373349

  11. Allergic Urticaria: A Case Report of Rare Skin Allergy with a Common Mouthwash

    PubMed Central

    Chopra, Viresh; Chopra, Harneet; Sharma, Anamika

    2013-01-01

    Chlorhexidine is a widely used antiseptic and disinfectant in medical and non-medical environments. Compared to its ubiquitous use, allergic contact dermatitis from chlorhexidine has rarely been reported and so its sensitization rate seems to be low. Chlorhexidine has been used for more than 50 years but it was only in the last two decades, that reports of immediate- type reactions to chlorhexidine were seen. Reactions ranging from localized urticaria to anaphylactic shock and hypersensitivity reactions, including delayed hypersensitivity reactions such as contact dermatitis, fixed drug eruptions, and photosensitivity reactions, began to appear more frequently. However the prevalence of contact urticaria and anaphylaxis due to chlorhexidine remains to be unknown. In this case report we have reported a case of urticaria due to oral use of chlorhexidine. The adverse reaction was confirmed by a skin prick test. PMID:23372227

  12. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2010-01-01

    This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. PMID:20109740

  13. Neuroimmune semaphorin 4A downregulates the severity of allergic response.

    PubMed

    Nkyimbeng-Takwi, E H; Shanks, K; Smith, E; Iyer, A; Lipsky, M M; Detolla, L J; Kikutani, H; Keegan, A D; Chapoval, S P

    2012-07-01

    To define the role of semaphorin 4A (Sema4A) in allergic response, we employed Sema4A⁻/⁻ and wild-type (WT) mice in the experimental model of ovalbumin (OVA)-induced allergic airway inflammation. We observed a selective increase in eosinophilic airway infiltration accompanied by bronchial epithelial cell hyperplasia in allergen-treated Sema4A⁻/⁻ mice relative to WT mice. This enhanced inflammatory response was associated with a selective increase in bronchoalveolar lavage (BAL) interleukin 13 (IL-13) content, augmented airway hyperreactivity, and lower regulatory T cell (Treg) numbers. In vivo allergen-primed Sema4A⁻/⁻ CD4+ T cells were more effective in transferring T helper type 2 (Th2) response to naive mice as compared with WT CD4+ T cells. T-cell proliferation and IL-13 productions in OVA₃₂₃₋₃₃₉-restimulated Sema4A⁻/⁻ cell cultures were upregulated. Generated bone marrow chimeras showed an equal importance of both lung-resident cell and inflammatory cell Sema4A expression in optimal disease regulation. These data provide a new insight into Sema4A biology and define Sema4A as an important regulator of Th2-driven lung pathophysiology. PMID:22472774

  14. [Allergic dermatitis caused by pyrogenic silica (aerosol)].

    PubMed

    Liashenko, I N; Lutsiuk, N B; Otkalenko, A K; Odnorogov, Iu V

    1989-01-01

    A case of allergic dermatitis developing after a contact exposure of the skin to aerosil is described. The authors suppose that violated intactness of the skin integument is largely responsible for the allergic reaction. The C-reactive protein, Hoigne's, and leucocyte migration inhibition tests have been all markedly positive. It is recommended that types of aerosil other than powder-forming be utilized and that means protecting the skin and the upper respiratory tract be used. PMID:2543155

  15. What is living on your dog's skin? Characterization of the canine cutaneous mycobiota and fungal dysbiosis in canine allergic dermatitis

    PubMed Central

    Meason-Smith, Courtney; Diesel, Alison; Patterson, Adam P.; Older, Caitlin E.; Mansell, Joanne M.; Suchodolski, Jan S.; Rodrigues Hoffmann, Aline

    2015-01-01

    To characterize the skin-associated fungal microbiota (mycobiota) in dogs, and to evaluate the influence of body site, individual dog or health status on the distribution of fungi, next-generation sequencing was performed targeting the internal transcribed spacer region. A total of 10 dogs with no history of skin disease were sampled at 10 distinct body sites consisting of haired and mucosal skin, and 8 dogs with diagnosed skin allergies were sampled at six body sites commonly affected by allergic disease. Analysis of similarities revealed that body site was not an influencing factor on membership or structure of fungal communities in healthy skin; however, the mucosal sites were significantly reduced in fungal richness. The mycobiota from body sites in healthy dogs tended to be similar within a dog, which was visualized in principle coordinates analysis (PCoA) by clustering of all sites from one dog separate from other dogs. The mycobiota of allergic skin was significantly less rich than that of healthy skin, and all sites sampled clustered by health status in PCoA. Interestingly, the most abundant fungi present on canine skin, across all body sites and health statuses, were Alternaria and Cladosporium—two of the most common fungal allergens in human environmental allergies. PMID:26542075

  16. What is living on your dog's skin? Characterization of the canine cutaneous mycobiota and fungal dysbiosis in canine allergic dermatitis.

    PubMed

    Meason-Smith, Courtney; Diesel, Alison; Patterson, Adam P; Older, Caitlin E; Mansell, Joanne M; Suchodolski, Jan S; Rodrigues Hoffmann, Aline

    2015-12-01

    To characterize the skin-associated fungal microbiota (mycobiota) in dogs, and to evaluate the influence of body site, individual dog or health status on the distribution of fungi, next-generation sequencing was performed targeting the internal transcribed spacer region. A total of 10 dogs with no history of skin disease were sampled at 10 distinct body sites consisting of haired and mucosal skin, and 8 dogs with diagnosed skin allergies were sampled at six body sites commonly affected by allergic disease. Analysis of similarities revealed that body site was not an influencing factor on membership or structure of fungal communities in healthy skin; however, the mucosal sites were significantly reduced in fungal richness. The mycobiota from body sites in healthy dogs tended to be similar within a dog, which was visualized in principle coordinates analysis (PCoA) by clustering of all sites from one dog separate from other dogs. The mycobiota of allergic skin was significantly less rich than that of healthy skin, and all sites sampled clustered by health status in PCoA. Interestingly, the most abundant fungi present on canine skin, across all body sites and health statuses, were Alternaria and Cladosporium--two of the most common fungal allergens in human environmental allergies. PMID:26542075

  17. AN EXTRACT OF PENICILLIUM CHRYSOGENUM INDUCES DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES IN MICE

    EPA Science Inventory

    Rationale: Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typ...

  18. Evaluation of Clinical and Immunological Responses: A 2-Year Follow-Up Study in Children with Allergic Rhinitis due to House Dust Mite

    PubMed Central

    Moed, Heleen; Gerth van Wijk, Roy; Hendriks, Rudi W.; van der Wouden, J. C.

    2013-01-01

    Background. Allergic rhinitis is a disease with polarization towards Th2 and a defect of regulatory T cells. Immunological changes have been reported after immunotherapy treatment. However, there is not much known about the natural course of allergic rhinitis with respect to clinical manifestation and the relation with immunological responses. Objective. To evaluate clinical symptoms of allergic rhinitis, in relation to in vivo allergen-specific skin responses and in vitro allergen-specific effector and regulatory T cells determined at baseline and after two years. Methods. From a large trial, 59 children were randomly selected. The following variables were compared: clinical symptoms, allergen skin tests, specific IgE, T-cell proliferation, IL-5, IL-13, IFN-gamma, IL-10, TGF-beta, CD4+CD25hi cells, and Foxp3 expression. Results. Allergic symptoms had decreased after two years. Whereas skin test reactions correlated between years 0 and 2, there was no change in the size of the reaction. Also, proinflammatory reactions did not change after two years, with a positive correlation between years 0 and 2. No relevant changes were observed with respect to regulatory cells. Conclusion. Whereas, comparable to immunotherapy, allergic complaints decrease, the immunological changes of specific T-cell activity (both effector cells and regulator cells) which are observed after immunotherapy, do not change. PMID:23737646

  19. Contribution of Basophils to Cutaneous Immune Reactions and Th2-Mediated Allergic Responses

    PubMed Central

    Otsuka, Atsushi; Kabashima, Kenji

    2015-01-01

    Basophils are potent effector cells of innate immunity and also play a role in T helper 2 (Th2)-mediated allergic responses. But, although their in vitro functions are well studied, their in vivo functions remain largely unknown. However, several mouse models of basophil depletion have recently been developed and used to investigate basophil functions. For example, in a croton oil-induced model of irritant contact dermatitis in conditionally basophil-depleted transgenic mice, we found that basophils rapidly infiltrate inflamed skin and subsequently induce infiltration of eosinophils. We also showed that basophils induce Th2 skewing upon epicutaneous sensitization with various haptens and peptide antigens. Intriguingly, basophils also promoted Th2 polarization upon protein antigen exposure in the presence of dendritic cells (DCs). The dermal DC subset associated with Th2 skewing was recently identified as CD301b+ DC. Such studies with basophil-deficient mouse models have significantly improved our understanding of the mechanisms involved in human immune-related diseases. In this review, we will focus on the relative contribution of basophils and DCs to Th2-mediated allergic responses. PMID:26284076

  20. Allergic manifestations and cutaneous histamine responses in patients with McCune Albright syndrome

    PubMed Central

    2013-01-01

    Background McCune Albright syndrome (MAS) is a rare disorder characterized by precocious puberty, café-au-lait spots, and fibrous dysplasia. Its cause is an activating mutation in the GNAS gene, encoding a subunit of the stimulatory G protein, Gsalpha (Gsα). The action of any mediator that signals via Gsα and cyclic AMP can be up regulated in MAS. We had observed gastritis, gastroesophageal reflux, and anaphylaxis in McCune Albright patients. Objective As histamine is known to signal via histamine 1 (H1) and histamine 2 (H2) receptors, which couple with stimulatory G proteins, we attempted to mechanistically link histamine responsiveness to the activating GNAS mutation. We hypothesized that responsiveness to histamine skin testing would differ between MAS patients and healthy controls. Patients and methods After obtaining informed consent, we performed a systematic review of histamine responsiveness and allergic manifestations in 11 MAS patients and 11 sex-matched, Tanner-stage matched controls. We performed skin prick testing, quantifying the orthogonal diameters of wheals and erythema. We also quantitated G protein mRNA expression. Results The peak wheal and flare responses to histamine were significantly higher in MAS patients compared to controls. Conclusions This study suggests that MAS patients may be at risk for exaggerated histamine responsiveness compared to unaffected controls. PMID:23663565

  1. Allergic rhinitis

    MedlinePlus

    ... your symptoms. Skin testing is the most common method of allergy testing. If your doctor determines you ... Others cause little or no sleepiness. Antihistamine nasal sprays work well for treating allergic rhinitis. Ask your ...

  2. 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

  3. Allergic contact dermatitis to plants: an analysis of 68 patients tested at the Skin and Cancer Foundation.

    PubMed

    Cook, D K; Freeman, S

    1997-08-01

    Allergic contact dermatitis to plant allergens is a common problem in Australia. We present the cumulative experience of the Contact Dermatitis Clinic of the Skin and Cancer Foundation (Darlinghurst, NSW, Australia) a tertiary referral clinic. Results from a series of 68 patients with positive patch tests to 88 plant allergens are reported. We found that Grevillea species, Compositae, Rhus, Alstroemeria and various timber sawdusts were the most common plant allergens. PMID:9293658

  4. 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...

  5. Positive skin prick tests of immediate type in non-allergic children.

    PubMed

    Cserháti, E; Kiss, A G; Mezei, G; Kelemen, J; Puskás, J

    1983-01-01

    Prick tests with twenty different Beneard antigens were performed in 300 children aged 2-16 years, all having a negative individual and familial history for allergic disease. At least one positive result was obtained in 64% of the children and among the 6000 tests a total of 727 were positive. Of the positive tests 93% were + or ++, 7% were +++ or ++++. No relationship was found between age and the incidence of positive skin tests. Mild reactions against more than one antigen in the same individual were quite frequent, pronounced reactions (+++ or ++++) against more than one antigen were exceptional. The incidence of mild reactions was found to be independent of the gender; strong reactions occurred in girls twice as often as in boys. The highest incidence of positive reactions was observed with house-dust mite, pollens, hay and straw dust, and canine and feline hairs. The diagnostic value of mild positivity is slight but pronounced positivity, especially against more than one antigen, must carefully be considered and in any case followed by a bronchial provocation test. PMID:6639791

  6. METALS, PARTICLES AND IMPACT UPON PULMONARY ALLERGIC RESPONSES

    EPA Science Inventory


    The increase in allergic asthma over the past few decades has prompted investigations into whether air pollution may affect either the incidence or severity of allergic lung disease. Population studies have demonstrated that as air pollution rises, symptoms, medication use a...

  7. 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 ...

  8. Local Immune Responses in Children and Adults with Allergic and Nonallergic Rhinitis

    PubMed Central

    Choi, Hana; Jang, Man-Young; Kim, Kyung Rae; Choi, Jae-Hoon; Cho, Seok Hyun

    2016-01-01

    Background Allergic rhinitis (AR) is the most common allergic disease but little is known about the difference of local immune responses in children and adults with AR. Objective To compare local immune responses between children and adults with AR and nonallergic rhinitis (NAR), and to investigate whether the association of local and systemic immune responses is different between the two age groups. Methods Fifty-one patients with chronic rhinitis were enrolled and grouped into children (N = 27, mean age 7.2 years) and adults (N = 24, mean age 29.9 years). Diagnosis of AR was based on symptoms, skin prick tests and serum specific IgEs. Nasal lavage (NAL) fluids were collected from all subjects and used to measure the levels of total IgE, specific IgEs to house dust mites (Dp and Df), and cytokines (TNF-α, IL-4, IL-10, IL-17A and IFN-γ). Flow cytometry was used to measure inflammatory cell types in NAL fluids. Results AR had significantly increased local levels of total IgE and specific IgEs to Dp and Df compared with NAR in both age groups (P < 0.05). Nasal eosinophils % (P = 0.01) was significantly increased only in children with AR. Local-systemic correlations of total IgE (r = 0.662, P = 0.000) and eosinophil % (r = 0.461, P = 0.015) between the peripheral blood and NAL fluids were found only in children. Moreover, children had correlations between total IgE and eosinophil % in the peripheral blood (r = 0.629, P = 0.001) and in NAL fluids (r = 0.373, P = 0.061). Conclusion Elevated local IgE is a common feature of AR in children and adults. Local measures in NAR showed naïve state of immune response which disagree with the hypothesis of local allergic rhinitis. Children showed intense local inflammation and close local-systemic interactions compared to adults supporting pediatric AR as a distinct feature. PMID:27281182

  9. Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma.

    PubMed

    Schmudde, Inken; Laumonnier, Yves; Köhl, Jörg

    2013-02-01

    Allergic asthma is a chronic disease of the airways in which maladaptive Th2 and Th17 immune responses drive airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Airway epithelial and pulmonary vascular endothelial cells in concert with different resident and monocyte-derived dendritic cells (DC) play critical roles in allergen sensing and consecutive activation of TH cells and their differentiation toward TH2 and TH17 effector or regulatory T cells (Treg). Further, myeloid-derived regulatory cells (MDRC) act on TH cells and either suppress or enhance their activation. The complement-derived anaphylatoxins (AT) C3a and C5a are generated during initial antigen encounter and regulate the development of maladaptive immunity at allergen sensitization. Here, we will review the complex role of ATs in activation and modulation of different DC populations, MDRCs and CD4⁺ TH cells. We will also discuss the potential impact of ATs on the regulation of the pulmonary stromal compartment as an important means to regulate DC functions. PMID:23694705

  10. Increased Allergic Immune Response to Sarcoptes scabiei Antigens in Crusted versus Ordinary Scabies▿

    PubMed Central

    Walton, Shelley F.; Pizzutto, Susan; Slender, Amy; Viberg, Linda; Holt, Deborah; Hales, Belinda J.; Kemp, David J.; Currie, Bart J.; Rolland, Jennifer M.; O'Hehir, Robyn

    2010-01-01

    Scabies, a parasitic skin infestation by the burrowing “itch” mite Sarcoptes scabiei, causes significant health problems for children and adults worldwide. Crusted scabies is a particularly severe form of scabies in which mites multiply into the millions, causing extensive skin crusting. The symptoms and signs of scabies suggest host immunity to the scabies mite, but the specific resistant response in humans remains largely uncharacterized. We used 4 scabies mite recombinant proteins with sequence homology to extensively studied house dust mite allergens to investigate a differential immune response between ordinary scabies and the debilitating crusted form of the disease. Subjects with either disease form showed serum IgE against recombinant S. scabiei cysteine and serine proteases and apolipoprotein, whereas naive subjects showed minimal IgE reactivity. Significantly (P < 0.05) greater serum IgE and IgG4 binding to mite apolipoprotein occurred in subjects with crusted scabies than in those with ordinary scabies. Both subject groups showed strong proliferative responses (peripheral blood mononuclear cells) to the scabies antigens, but the crusted scabies group showed increased secretion of the Th2 cytokines interleukin 5 (IL-5) and IL-13 and decreased Th1 cytokine gamma interferon (IFN-γ) in response to the active cysteine protease. These data confirm that a nonprotective allergic response occurs in the crusted disease form and demonstrate that clinical severity is associated with differences in the type and magnitude of the antibody and cellular responses to scabies proteins. A quantitative IgE inhibition assay identified IgE immunoreactivity of scabies mite antigens distinct from that of house dust mite antigens, which is potentially important for specific scabies diagnosis and therapy. PMID:20631334

  11. Increased allergic immune response to Sarcoptes scabiei antigens in crusted versus ordinary scabies.

    PubMed

    Walton, Shelley F; Pizzutto, Susan; Slender, Amy; Viberg, Linda; Holt, Deborah; Hales, Belinda J; Kemp, David J; Currie, Bart J; Rolland, Jennifer M; O'Hehir, Robyn

    2010-09-01

    Scabies, a parasitic skin infestation by the burrowing "itch" mite Sarcoptes scabiei, causes significant health problems for children and adults worldwide. Crusted scabies is a particularly severe form of scabies in which mites multiply into the millions, causing extensive skin crusting. The symptoms and signs of scabies suggest host immunity to the scabies mite, but the specific resistant response in humans remains largely uncharacterized. We used 4 scabies mite recombinant proteins with sequence homology to extensively studied house dust mite allergens to investigate a differential immune response between ordinary scabies and the debilitating crusted form of the disease. Subjects with either disease form showed serum IgE against recombinant S. scabiei cysteine and serine proteases and apolipoprotein, whereas naive subjects showed minimal IgE reactivity. Significantly (P < 0.05) greater serum IgE and IgG4 binding to mite apolipoprotein occurred in subjects with crusted scabies than in those with ordinary scabies. Both subject groups showed strong proliferative responses (peripheral blood mononuclear cells) to the scabies antigens, but the crusted scabies group showed increased secretion of the Th2 cytokines interleukin 5 (IL-5) and IL-13 and decreased Th1 cytokine gamma interferon (IFN-gamma) in response to the active cysteine protease. These data confirm that a nonprotective allergic response occurs in the crusted disease form and demonstrate that clinical severity is associated with differences in the type and magnitude of the antibody and cellular responses to scabies proteins. A quantitative IgE inhibition assay identified IgE immunoreactivity of scabies mite antigens distinct from that of house dust mite antigens, which is potentially important for specific scabies diagnosis and therapy. PMID:20631334

  12. Secondary allergic T cell responses are regulated by dendritic cell-derived thrombospondin-1 in the setting of allergic eye disease.

    PubMed

    Smith, R E; Reyes, N J; Khandelwal, P; Schlereth, S L; Lee, H S; Masli, S; Saban, D R

    2016-08-01

    Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin-1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with naïve T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell-derived thrombospondin-1 expression as a factor in allergic eye disease severity. PMID:26856994

  13. No Adjuvant Effect of Bacillus thuringiensis-Maize on Allergic Responses in Mice

    PubMed Central

    Dekan, Gerhard; Epstein, Michelle M.

    2014-01-01

    Genetically modified (GM) foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt)-maize (MON810) on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA)-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma. PMID:25084284

  14. [The incidence of occupationally-induced allergic skin diseases in a large flower market].

    PubMed

    Hausen, B M; Oestmann, G

    1988-01-01

    150 questionnaires as well as epicutaneous tests in 56 individuals from a total of 675 persons cultivating and selling ornamental plants at the largest German flower market revealed that half of those investigated were suffering from allergic contact dermatitis. The leading plant species with sensitizing properties was found to be the chrysanthemum, followed by tulips and Alstroemeria cultivars. Allergic reactions to daffodils and primulas were rarely observed. Most of the reactions obtained with other Compositae species such as arnica, marguerite, sunflower, tansy and yarrow must be interpreted as cross-reactions due to the fact that cross-reactivity predominates within the sesquiterpene lactone constituents of the various Compositae species. PMID:2971519

  15. Allergic skin inflammation induced by chemical sensitizers is controlled by the transcription factor Nrf2.

    PubMed

    El Ali, Zeina; Gerbeix, Cédric; Hemon, Patrice; Esser, Philipp R; Martin, Stefan F; Pallardy, Marc; Kerdine-Römer, Saadia

    2013-07-01

    Allergic contact dermatitis (ACD) is induced by low-molecular weight electrophilic chemicals and metal ions. Chemical contact sensitizers trigger reactive oxygen species production and provoke electrophilic stress, leading to the accumulation of the transcription factor nuclear-related factor 2 (Nrf2) in innate immune cell types. The objective of this work was to identify the role of Nrf2 in the regulation of ACD. We used the local lymph node assay (LLNA) and the mouse ear swelling test (MEST) to study the role of Nrf2 in both the sensitization and elicitation phase in nrf2 knockout (nrf2(-/-)) and wild-type (nrf2(+/+)) mice. Five chemicals were used: two compounds known to react with cysteine residues, 2,4-dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA); one sensitizer known to exhibit mixed reactivity to cysteine and lysine residues, isophorone diisocyanate; and one reacting specifically with lysine residues, trimellitic anhydride and croton oil, a well-known irritant. In the MEST assay, DNCB (1 and 2%) induced a significant increase in ear thickness in nrf2(-/-) compared with nrf2(+/+) mice, suggesting a role for Nrf2 in the control of the inflammatory process. When DNCB was used at 0.25 and 0.5% or when mice were treated with CinA, inflammation was found only in nrf2(-/-) mice. In the LLNA, all chemical sensitizers induced an increase of lymphocyte proliferation in nrf2(-/-) compared with nrf2(+/+) mice for the same chemical concentration. These results reveal an important role for Nrf2 in controlling ACD and lymphocyte proliferation in response to sensitizers. PMID:23564646

  16. 21 CFR 882.1540 - Galvanic skin response measurement device.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Galvanic skin response measurement device. 882... Galvanic skin response measurement device. (a) Identification. A galvanic skin response measurement device... electrical resistance of the skin and the tissue path between two electrodes applied to the skin....

  17. 21 CFR 882.1540 - Galvanic skin response measurement device.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Galvanic skin response measurement device. 882... Galvanic skin response measurement device. (a) Identification. A galvanic skin response measurement device... electrical resistance of the skin and the tissue path between two electrodes applied to the skin....

  18. 21 CFR 882.1540 - Galvanic skin response measurement device.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Galvanic skin response measurement device. 882... Galvanic skin response measurement device. (a) Identification. A galvanic skin response measurement device... electrical resistance of the skin and the tissue path between two electrodes applied to the skin....

  19. 21 CFR 882.1540 - Galvanic skin response measurement device.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Galvanic skin response measurement device. 882... Galvanic skin response measurement device. (a) Identification. A galvanic skin response measurement device... electrical resistance of the skin and the tissue path between two electrodes applied to the skin....

  20. Levocetirizine: a review of its use in the management of allergic rhinitis and skin allergies.

    PubMed

    Hair, Philip I; Scott, Lesley J

    2006-01-01

    Levocetirizine (Xyzal) is a selective, potent, oral histamine H(1) receptor antagonist of the latest generation that is licensed for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis [PER]) and chronic idiopathic urticaria (CIU). Large, well designed trials indicate that levocetirizine is effective and generally well tolerated in the treatment of allergic rhinitis and CIU. Its pharmacological profile offers many positive aspects: a rapid onset and long duration of antihistaminic effect; rapid absorption and high bioavailability; a low potential for drug interactions; a low volume of distribution; and a lack of effect on cognition, psychomotor function and the cardiovascular system. Allergen challenge chamber studies suggest that levocetirizine has better efficacy than desloratadine, loratadine or fexofenadine. Well controlled, long-term studies with other later-generation H(1) receptor antagonists are required to fully define its clinical profile relative to other agents in this class. Overall, levocetirizine is a valuable addition to the oral H(1) receptor antagonists available for the treatment of allergic rhinitis and as first-line therapy in patients with CIU. PMID:16740020

  1. Lymphocyte responses to food antigens in food sensitive patients with allergic tension-fatigue syndrome.

    PubMed

    Kondo, N; Shinoda, S; Agata, H; Nishida, T; Miwa, Y; Fujii, H; Orii, T

    1992-01-01

    Scores of radioallergosorbent test (RAST) for cow's milk or buckwheat flour and proliferative responses of peripheral blood mononuclear cells (PBMCs) to bovine serum albumin and beta-lactoglobulin or buckwheat flour were measured in cow's milk or buckwheat flour sensitive patients with allergic tension-fatigue syndrome. In all 3 cow's milk sensitive patients with allergic tension-fatigue syndrome, RAST scores for cow's milk were negative or slightly positive, but PBMCs well responded to bovine serum albumin and beta-lactoglobulin, but not to ovalbumin. In a buckwheat flour sensitive patient with allergic tension-fatigue syndrome, RAST scores for buckwheat flour were negative, but PBMCs well responded to buckwheat flour, but not to ovalbumin, bovine serum albumin and beta-lactoglobulin. Conversely, in cow's milk or buckwheat flour sensitive patients with immediate allergic symptoms, RAST scores for offending foods were positive although PBMCs did not respond to offending food antigens. These results suggest that proliferative responses of PBMCs to food antigens are very useful for detection of offending foods in allergic tension-fatigue syndrome. PMID:1290724

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

    PubMed

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

    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(++) influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. PMID:23994558

  3. What if skin eruption is not caused by allergic reaction to drugs?

    PubMed

    Bobik, O; Bobik, O; Arganova, H

    2010-01-01

    In this case report authors have described a case of a 39 years old Caucasian single man who was unsuccessfully treated for an allergic reaction to drugs by multiple dermatologists, due to two etiologically different diseases. It was a classical second stage syphilitic infection and positive serologic tests for HIV infection, proved by screening and confirmatory tests. Syphilitic infection was treated and followed up by dermatologist and for the treatment of HIV infection, the patient was referred to the Centre for treatment HIV/AIDS in Kosice (Fig. 4, Ref. 3). PMID:20586153

  4. 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

  5. T follicular helper (Tfh ) cells in normal immune responses and in allergic disorders.

    PubMed

    Varricchi, G; Harker, J; Borriello, F; Marone, G; Durham, S R; Shamji, M H

    2016-08-01

    Follicular helper T cells (Tfh ) are located within germinal centers of lymph nodes. Cognate interaction between Tfh , B cells, and IL-21 drives B cells to proliferate and differentiate into plasma cells thereby leading to antibody production. Tfh cells and IL-21 are involved in infectious and autoimmune diseases, immunodeficiencies, vaccination, and cancer. Human peripheral blood CXCR5(+) CD4(+) T cells comprise different subsets of Tfh -like cells. Despite the importance of the IgE response in the pathogenesis of allergic disorders, little is known about the role of follicular and blood Tfh cells and IL-21 in human and experimental allergic disease. Here, we review recent advances regarding the phenotypic and functional characteristics of both follicular and blood Tfh cells and of the IL-21/IL-21R system in the context of allergic disorders. PMID:26970097

  6. EFFECTS OF PARTICLES FROM TWO GERMAN CITIES ON ALLERGIC RESPONSES IN MICE

    EPA Science Inventory

    EFFECTS OF PARTICLES FROM TWO GERMAN CITIES ON ALLERGIC RESPONSES IN MICE. S. H. Gavett, L. R. Bishop, N. Haykal-Coates, J. Heinrich*, and M. I. Gilmour. Experimental Toxicology Division, ORD/NHEERL, U.S. EPA, Research Triangle Park, NC, USA, *GSF, Neuherberg, Germany.
    Chi...

  7. 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 ...

  8. 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...

  9. Lipopolysaccharide exposure makes allergic airway inflammation and hyper-responsiveness less responsive to dexamethasone and inhibition of iNOS.

    PubMed

    Komlósi, Z I; Pozsonyi, E; Tábi, T; Szöko, E; Nagy, A; Bartos, B; Kozma, G T; Tamási, L; Orosz, M; Magyar, P; Losonczy, G

    2006-07-01

    Allergic airway disease can be refractory to anti-inflammatory treatment, whose cause is unclarified. Therefore, in the present experiment, we have tested the hypothesis that co-exposure to lipopolysacharide (Lps) and allergen results in glucocorticoid-resistant eosinophil airway inflammation and hyper-responsiveness (AHR). Ovalbumin (Ova)-sensitized BALB/c mice were primed with 10 microg intranasal Lps 24 h before the start of Ova challenges (20 min on 3 consecutive days). Dexamethasone (5 mg/kg/day) was given on the last 2 days of Ova challenges. AHR, cellular build-up, cytokine and nitrite concentrations of bronchoalveolar lavage fluid (BALF) and lung histology were examined. To assess the role of iNOS-derived NO in airway responsiveness, mice were treated with a selective inhibitor of this enzyme (1400W) 2 h before AHR measurements. More severe eosinophil inflammation and higher nitrite formation were found in Lps-primed than in non-primed allergized mice. After Lps priming, AHR and concentrations of T-helper type 2 cytokines in BALF were decreased, but still remained significantly higher than in controls. Eosinophil inflammation was partially, while nitrite production and AHR were observed to be largely dexamethasone resistant in Lps-primed allergized animals. 1400W effectively and rapidly diminished the AHR in Ova-sensitized and challenged mice, but failed to affect it after Lps priming plus allergization. In conclusion, Lps inhalation may exaggerate eosinophil inflammation and reduce responsiveness to anti-inflammatory treatment in allergic airway disease. PMID:16839411

  10. Toxoplasma gondii infection modulate systemic allergic immune response in BALB/c mice.

    PubMed

    Fenoy, Ignacio M; Sánchez, Vanesa R; Soto, Ariadna S; Picchio, Mariano S; Martin, Valentina; Goldman, Alejandra

    2015-07-01

    The increased prevalence of allergies in developed countries has been attributed to a reduced exposure to some microbes. In agreement with epidemiological studies, we previously showed that Toxoplasma gondii infection prevents allergic airway inflammation. The mechanisms would be related to the strong Th1 response induced by the parasite and to regulatory cell induction. Herein we further characterized whether T. gondii allergy modulation extents to a systemic level or if it is limited to the lung. Parasite infection before allergic sensitization resulted in a diminished Th2 cytokine response and, when sensitized during acute infection, an increased in TGF-β production was detected. Allergen specific T cell proliferation was also reduced. Sensitization during both acute and chronic phases of infection resulted in a decreased anaphylaxis reaction. Our results extend earlier work and show that, in addition to lung airway inflammation, T. gondii infection can suppress allergic responses at systemic level. These results open the possibility that this protozoan infection could modulate other allergic disorders such as atopic dermatitis or oral allergies. Understanding the mechanisms by which different microorganisms regulate inflammation may potentially lead to the development of strategies aimed to control atopic diseases. PMID:25888245

  11. SUPPRESSION OF ALLERGIC IMMUNE RESPONSES TO HOUSE DUST MITE (HDM) IN RATS EXPOSED TO 2,3,7,8-TCDD

    EPA Science Inventory

    Abstract
    Exposure to various xenobiotics, including oxidant gases, diesel exhaust and certain pesticides, has been reported to exacerbate pulmonary allergic hypersensitivity responses. Increased lymphocyte proliferative responses to parasite antigens or increased antibody r...

  12. Allergic rhinitis

    PubMed Central

    2011-01-01

    Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually a long-standing condition that often goes undetected in the primary-care setting. The classic symptoms of the disorder are nasal congestion, nasal itch, rhinorrhea and sneezing. A thorough history, physical examination and allergen skin testing are important for establishing the diagnosis of allergic rhinitis. Second-generation oral antihistamines and intranasal corticosteroids are the mainstay of treatment. Allergen immunotherapy is an effective immune-modulating treatment that should be recommended if pharmacologic therapy for allergic rhinitis is not effective or is not tolerated. This article provides an overview of the pathophysiology, diagnosis, and appropriate management of this disorder. PMID:22166009

  13. CTAB-coated gold nanorods elicit allergic response through degranulation and cell death in human basophils

    NASA Astrophysics Data System (ADS)

    Cheung, Ka Lun; Chen, Huanjun; Chen, Qiulan; Wang, Jianfang; Ho, Ho Pui; Wong, Chun Kwok; Kong, Siu Kai

    2012-07-01

    The effect of CTAB (cetyltrimethylammonium bromide)- or PEG (polyethylene glycol)-coated gold-nanorods (Au-NRs) on the non-IgE mediated allergic response was studied. We found that the CTAB-Au-NRs released more allergic mediators such as histamine and β-hexosaminidase from human basophil KU812, a common model for studying allergy, after 20 min incubation. Also, the CTAB-Au-NRs induced more apoptosis than the PEG-Au-NRs in KU812 24 h after treatment. These short- and long-term effects were not solely due to the CTAB residues in the supernatant desorbed from the Au-NRs.The effect of CTAB (cetyltrimethylammonium bromide)- or PEG (polyethylene glycol)-coated gold-nanorods (Au-NRs) on the non-IgE mediated allergic response was studied. We found that the CTAB-Au-NRs released more allergic mediators such as histamine and β-hexosaminidase from human basophil KU812, a common model for studying allergy, after 20 min incubation. Also, the CTAB-Au-NRs induced more apoptosis than the PEG-Au-NRs in KU812 24 h after treatment. These short- and long-term effects were not solely due to the CTAB residues in the supernatant desorbed from the Au-NRs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr30435j

  14. Allergic rhinitis.

    PubMed

    Mygind, Niels

    2014-01-01

    Allergic rhinitis is a very frequent disease with a prevalence of 15-20%. Symptoms are most pronounced in young people while, for some unknown reason, the elderly become clinically hyposensitized. Pollen is the cause of seasonal allergic rhinitis, and house dust mite and animals are the main causes of perennial allergic rhinitis. Histamine is the main cause of sneezing and hypersecretion, while other mediators probably also play a role in nasal blockage. In polyposis, a local denervation is an important cause of vascular leakage, edema and polyp formation. Antihistamines have a positive effect on sneezing and hypersecretion, but not on blockage. As they have a quick onset of action they are useful in patients with mild and occasional symptoms. A nasal steroid is preferable in patients with persistent symptoms, since it is more effective on all nasal symptoms. Short-term use of a systemic steroid can be a valuable adjunct to topical treatment, especially in nasal polyposis, when there is a temporary failure of topical treatment in a blocked nose. A nasal vasoconstrictor can be added for short-term treatment, and an ipratropium spray can be beneficial in perennial non-allergic rhinitis, when watery secretion is the dominant symptom. Immunotherapy can be added in allergic rhinitis, when pharmacotherapy is insufficient. This chapter is based on the author's personal experience with allergic rhinitis, as a patient, a doctor and a researcher. Therefore, it is not a balanced review and the references will be highly selected as they largely consist of the author's own publications. As the text is mainly based on personal research, steroids are described in detail, while, with regard to immunotherapy, the reader is referred to another chapter. In addition to allergic rhinitis, nasal polyposis will be described. It was formerly believed to be an allergic disease, but we now know that it is not. However, with regard to histopathology and drug responsiveness this disease is

  15. Allergic Non-Asthmatic Adults Have Regional Pulmonary Responses to Segmental Allergen Challenge

    PubMed Central

    Kelly, Vanessa J.; Winkler, Tilo; Venegas, Jose G.; Kone, Mamary; Hamilos, Daniel L.; Afshar, Roshi; Cho, Josalyn L.; Luster, Andrew D.; Medoff, Benjamin D.; Harris, R. Scott

    2015-01-01

    Background Allergic non-asthmatic (ANA) adults experience upper airway symptoms of allergic disease such as rhinorrhea, congestion and sneezing without symptoms of asthma. The aim of this study was to utilize PET-CT functional imaging to determine whether allergen challenge elicits a pulmonary response in ANA subjects or whether their allergic disease is truly isolated to the upper airways. Methods In 6 ANA subjects, bronchoalveolar lavages (BAL) were performed at baseline and 24h after instillation of an allergen and a diluent in separate lung lobes. After instillation (10h), functional imaging was performed to quantify and compare regional perfusion, ventilation, fractional gas content (Fgas), and glucose uptake rate (Ki) between the baseline, diluent and allergen lobes. BAL cell counts were also compared. Results In ANA subjects, compared to the baseline and diluent lobes, perfusion and ventilation were significantly lower in the allergen lobe (median [inter-quartile range], baseline vs. diluent vs. allergen: Mean-normalized perfusion; 0.87 [0.85–0.97] vs. 0.90 [0.86–0.98] vs. 0.59 [0.55–0.67]; p<0.05. Mean-normalized ventilation 0.89 [0.88–0.98] vs. 0.95 [0.89–1.02] vs. 0.63 [0.52–0.67], p<0.05). In contrast, no significant differences were found in Fgas between baseline, diluent and allergen lobes or in Ki. Total cell counts, eosinophil and neutrophil cell counts (cells/ml BAL) were significantly greater in the allergen lobe compared to the baseline lobe (all P<0.05). Conclusions Despite having no clinical symptoms of a lower airway allergic response (cough and wheeze) allergic non-asthmatic subjects have a pulmonary response to allergen exposure which manifests as reduced ventilation and perfusion. PMID:26640951

  16. Respiratory syncytial virus replication is prolonged by a concomitant allergic response

    PubMed Central

    Hassantoufighi, A; Oglesbee, M; Richter, B W M; Prince, G A; Hemming, V; Niewiesk, S; Eichelberger, M C

    2007-01-01

    Epidemiological studies show an association between early exposure to respiratory syncytial virus (RSV) and the development or exacerbation of asthma. This idea is supported by studies in mice that demonstrate worsened airway hyper-reactivity (AHR) when RSV-infected animals are exposed to allergen. The effect of allergen on RSV disease, however, has not been reported. Cotton rats (Sigmodon hispidus) that have been used as a model to study RSV pathogenesis were sensitized to extracts of Aspergillus fumigatus (Af), a common household mould. The allergic response to Af included eosinophilia, formation of granulomas and induction of Th2 type cytokines. RSV infection prior to allergen challenge resulted in exacerbation of the inflammatory response as well as increased airway responsiveness to methacholine. The exacerbated response was indeed dependent on virus replication. Virus replication in turn was influenced by the allergic response, with persistence in the noses for 2 days longer in animals challenged with allergen. This diminished clearance corresponded to decreased induction of mRNA for IFN-γ, a Th1-type cytokine that is characteristic of viral infection. Treatment of RSV-infected Af-challenged animals with recombinant IFN-γ reduced the allergic inflammatory response as well as the relative levels of Th1 and Th2 cytokine mRNA. However, this treatment did not reduce airway reactivity, showing that these pathologic and physiologic measures of exacerbated disease are independent. We speculate that the reciprocal effect of the allergic response on viral immunity may benefit the host by limiting exacerbation of physiologic responses that are IFN-γ-dependent. PMID:17335559

  17. "Siglec"ting the allergic response for therapeutic targeting.

    PubMed

    Bochner, Bruce S

    2016-06-01

    As a physician-scientist, I have pursued research related to translational immunology with the goal of improving our ability to diagnose and treat allergic, immunologic and other diseases involving eosinophils, basophils and mast cells. We have tried to delineate novel mechanisms of human disease, working whenever possible with primary human cells and tissues, attempting to identify targets that might be amenable to the development of new therapies. As a general strategy, we have compared eosinophils, basophils, mast cells and neutrophils to look for pathways in inflammation that were unique to distinct subsets of these cells. In doing so, the concepts of glycobiology did not enter my mind until we began noticing some intriguing functional differences involving selectins and their ligands among these cell types. One simple observation, that neutrophils were coated with a glycan that allowed them to interact with an endothelial adhesion molecule while eosinophils lacked this structure, pried open the glyco-door for me. Fruitful collaborations with card-carrying glycobiologists soon followed that have forever positively influenced our science, and have enhanced our hypotheses, experimental design, research opportunities and discoveries. Within a few years, we helped to discover Siglec-8, an I-type lectin expressed only on human eosinophils, basophils, mast cells. This receptor, together with its closest mouse counterpart Siglec-F, has been the primary focus of our work now for over a decade. If not for those in the fields of glycobiology and glycoimmunology, my lab would not have made much progress toward the goal of leveraging Siglec-8 for therapeutic purposes. PMID:26911285

  18. 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...

  19. Booster responses in the study of allergic reactions to beta-lactam antibiotics.

    PubMed

    Lopez-Serrano, M C; Caballero, M T; Barranco, P; Martinez-Alzamora, F

    1996-01-01

    The observation of negative skin and challenge tests to beta-lactams in some patients with prior histories of reactions to these antibiotics led us to develop a protocol ("booster study") which systematically included the performance of skin and challenge tests to beta-lactams ten to thirty days after the study to confirm the negative results. From a total of 430 patients who came to our outpatient clinic because of a reaction to a beta-lactam or unknown antibiotic, 249 completed the study. Out of the patients who completed the second phase, or "booster study," the results were positive in the first phase, or conventional study in 42 patients, and negative in 207. The booster study was negative in 197 patients (95 percent) and positive in ten patients (5 percent). Skin tests were positive in 5 of them (penicilloyl-polylysine: 5; benzylpenicillin: 3; amoxicillin: 2; minor determinant mixture: 1), and 5 patients developed an allergic reaction after rechallenge (benzylpenicillin: 4; amoxicillin: 1). One patient with both negative skin tests and amoxicillin oral challenge in the booster study developed an immediate generalized urticaria with the oral intake of amoxicillin one month later at home; skin tests became positive at that moment. The negative results in the first phase of the study and the development of positive results in the second phase could be due to the existence of an immunological amnestic reaction or to sensitization after reexposure to beta-lactams in the diagnostic procedures. PMID:8833166

  20. Aspergillus fumigatus-specific antibodies in allergic bronchopulmonary aspergillosis and aspergilloma: evidence for a polyclonal antibody response.

    PubMed Central

    Brummund, W; Resnick, A; Fink, J N; Kurup, V P

    1987-01-01

    Patients with the Aspergillus-induced diseases allergic bronchopulmonary aspergillosis (ABPA), aspergilloma (fungus ball), and Aspergillus skin test-positive asthma were differentiated immunologically by radioimmunoassay based on their total immunoglobulin E (IgE) and Aspergillus fumigatus-specific IgE levels. In this study, a new, highly sensitive biotin-avidin-linked immunosorbent assay was used to evaluate A. fumigatus-specific antibodies of all immunoglobulin classes. Studied populations included 13 patients with ABPA, 12 with aspergilloma, 9 with Aspergillus skin test-positive asthma, and 9 normal individuals without asthma. A. fumigatus-specific antibodies of all classes were elevated in patients with ABPA, variably elevated in those with aspergilloma, and lowest in the other two groups. This assay demonstrated significantly higher specific IgE antibody levels in the ABPA group over those of the other groups, even with 1:1,000 dilutions of the sera. This study demonstrated that ABPA is a disease characterized by a polyclonal antibody response to Aspergillus antigen and not just a response to IgE and IgG antibody classes. The measurement of other antibody classes, particularly IgD and IgA, could enhance the immunodiagnosis of ABPA. The biotin-avidin-linked immunosorbent assay was found to be a highly sensitive assay that can be a clinically useful alternative to radioimmunoassay in the measurement of A. fumigatus-specific antibodies. PMID:3539998

  1. Abnormal IgG4 antibody response to aeroallergens in allergic patients.

    PubMed

    Jeannin, P; Delneste, Y; Tillie-Leblond, I; Wallaert, B; carlier, A; Pestel, J; Tonnel, A B

    1994-01-01

    Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders. PMID:8199463

  2. Residual oil fly ash amplifies allergic cytokines, airway responsiveness, and inflammation in mice.

    PubMed

    Gavett, S H; Madison, S L; Stevens, M A; Costa, D L

    1999-12-01

    Particulate matter (PM) air pollution may increase symptom severity in allergic asthmatics. To examine possible interaction, or greater than additive responses, between PM effects and allergic responses, an ovalbumin-sensitized and challenged (OVA) mouse model of allergic airways disease was utilized. After challenge, mice were intratracheally instilled with saline vehicle or 3 mg/kg (approximately 60 microg) residual oil fly ash (ROFA), a transition metal-rich emission source PM sample. Physiological and inflammatory responses were examined 1, 3, 8, and 15 d later. In response to intravenously administered methacholine, ROFA increased total respiratory system resistance and decreased compliance 1 d after exposure, whereas effects of OVA lasted at least 15 d after exposure. Significant interactions between OVA and ROFA were mainly observed 8 d after challenge and exposure, especially with respect to compliance. A strong interaction (p < 0.01) between OVA and ROFA exposure resulted in 8-fold (1 d) and 3-fold (3 d) increases in bronchoalveolar lavage (BAL) fluid eosinophil numbers. A similarly strong interaction (8-fold) was observed in BAL fluid interleukin-4 (IL-4) 1 d after challenge and exposure. Significant though less strong interactions were also found with respect to IL-4 and IL-5 by 3 d postchallenge/exposure. This study shows that allergen challenge and exposure to emission source particulate matter containing relatively high levels of transitions metals can interact to increase Th2 cytokine production, eosinophil recruitment, and airway hyperresponsiveness in previously sensitized mice. PMID:10588603

  3. 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

  4. 21 CFR 882.1540 - Galvanic skin response measurement device.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Galvanic skin response measurement device. 882.1540 Section 882.1540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Galvanic skin response measurement device. (a) Identification. A galvanic skin response measurement...

  5. 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. ...

  6. Oral supplementation with areca-derived polyphenols attenuates food allergic responses in ovalbumin-sensitized mice

    PubMed Central

    2013-01-01

    Background Arecae semen, the dried slice of areca nuts, is a traditional Chinese medicine used to treat intestinal parasitosis, rectal tenesmus and diarrhea. Areca nuts contain a rich amount of polyphenols that have been shown to modulate the functionality of mast cells and T cells. The objective of this study is to investigate the effect of polyphenol-enriched areca nut extracts (PANE) against food allergy, a T cell-mediated immune disorder. Methods BALB/c mice were left untreated or administered with PANE (0.05% and 0.1%) via drinking water throughout the entire experiment. The mice were sensitized with ovalbumin (OVA) twice by intraperitoneal injection, and then repeatedly challenged with OVA by gavage to induce food allergic responses. Results PANE administration attenuated OVA-induced allergic responses, including the occurrence of diarrhea and the infiltration and degranulation of mast cells in the duodenum. The serum level of OVA-specific IgE and the expression of interleukin-4 in the duodenum were suppressed by PANE treatment. In addition, PANE administration induced Gr-1+, IL-10+ and Gr-1+IL-10+ cells in the duodenum. Conclusion These results demonstrate that oral intake of areca-derived polyphenols attenuates food allergic responses accompanied with a decreased Th2 immunity and an enhanced induction of functional myeloid-derived suppressor cells. PMID:23816049

  7. 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

  8. Thioredoxin-linked mitigation of allergic responses to wheat

    PubMed Central

    Buchanan, B. B.; Adamidi, C.; Lozano, R. M.; Yee, B. C.; Momma, M.; Kobrehel, K.; Ermel, R.; Frick, O. L.

    1997-01-01

    Thioredoxin, a ubiquitous 12-kDa regulatory disulfide protein, was found to reduce disulfide bonds of allergens (convert S—S to 2 SH) and thereby mitigate the allergenicity of commercial wheat preparations. Allergenic strength was determined by skin tests with a canine model for food allergy. Statistically significant mitigation was observed with 15 of 16 wheat-sensitive animals. The allergenicity of the protein fractions extracted from wheat flour with the indicated solvent was also assessed: the gliadins (ethanol) were the strongest allergens, followed by glutenins (acetic acid), albumins (water), and globulins (salt water). Of the gliadins, the α and β fractions were most potent, followed by the γ and ω types. Thioredoxin mitigated the allergenicity associated with the major protein fractions—i.e, the gliadins (including the α, β, and γ types) and the glutenins—but gave less consistent results with the minor fractions, the albumins and globulins. In all cases, mitigation was specific to thioredoxin that had been reduced either enzymically by NADPH and NADP–thioredoxin reductase or chemically by dithiothreitol; reduced glutathione was without significant effect. As in previous studies, thioredoxin was particularly effective in the reduction of intramolecular (intrachain) disulfide bonds. The present results demonstrate that the reduction of these disulfide bonds is accompanied by a statistically significant decrease in allergenicity of the active proteins. This decrease occurs alongside the changes identified previously—i.e., increased susceptibility to proteolysis and heat, and altered biochemical activity. The findings open the door to the testing of the thioredoxin system in the production of hypoallergenic, more-digestible foods. PMID:9144244

  9. Effect of ozone inhalation on the response to nasal challenge with antigen of allergic subjects

    SciTech Connect

    Bascom, R.; Naclerio, R.M.; Fitzgerald, T.K.; Kagey-Sobotka, A.; Proud, D. )

    1990-09-01

    The effect of oxidant inhalation on allergic illness is of interest because allergic patients often report increased respiratory symptoms during episodes of poor air quality, and epidemiologic studies demonstrate an association between increased levels of the air pollutant ozone and exacerbations of asthma. The purpose of this study was to characterize the upper respiratory response to ozone inhalation in asymptomatic, allergic subjects and to determine whether ozone pre-exposure increased the acute response to nasal challenge with antigen in these subjects. A group of 12 asymptomatic subjects with a history of allergic rhinitis were exposed in a randomized, cross-over design, at rest, on each of 2 days, separated by 2 wk, to 4 h of clean air or 0.5 ppm ozone in an environmental chamber. Following the exposure period, subjects underwent nasal challenge with four doses of antigen (1 to 1,000 PNU ragweed or grass). Symptoms were rated and nasal lavage performed after each dose. Measurement of histamine and albumin concentration and TAME-esterase activity and determination of cell counts and differentials were performed. Exposure to ozone caused significant increases in upper and lower respiratory symptoms, a mixed inflammatory cell influx with a sevenfold increase in naval lavage neutrophils, a 20-fold increase in eosinophils, and a tenfold increase in mononuclear cells, as well as an apparent sloughing of epithelial cells. There was a significant increase in nasal lavage albumin concentration on the ozone exposure day and a small increase in nasal lavage histamine concentration on both the ozone and clean air exposure days. TAME-esterase activity showed no significant increase overall, but increased at least twofold in 5 of 12 subjects.

  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. 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 ...

  12. Adoptive transfer of allergic airway responses with sensitized lymphocytes in BN rats.

    PubMed

    Watanabe, A; Rossi, P; Renzi, P M; Xu, L J; Guttmann, R D; Martin, J G

    1995-07-01

    To evaluate the role of lymphocytes in the pathogenesis of allergic bronchoconstriction, we investigated whether allergic airway responses are adoptively transferred by antigen-primed lymphocytes in Brown Norway (BN) rats. Animals were actively sensitized to ovalbumin (OA) or sham sensitized, and 14 d later mononuclear cells (MNCs) were isolated from intrathoracic lymph nodes, passed through a nylon wool column, and transferred to naive syngeneic rats. Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells. Recipients of MNCs from sensitized rats responded to OA inhalation and exhibited sustained increases in RL throughout the 8-h observation period, but without usual early airway responses. Recipients of sham-sensitized MNCs or BSA-challenged recipients failed to respond to antigen challenge. At 32 h after OA exposure, airway responsiveness to MCh was increased in four of seven rats that had received sensitized MNCs (p = 0.035). BAL eosinophils increased at 32 h in the recipients of both sensitized and sham-sensitized MNCs. However, eosinophil numbers in BAL were inversely correlated with airway responsiveness in the recipients of sensitized MNCs (r = -0.788, p = 0.036). OA-specific immunoglobulin E (IgE) was undetectable by enzyme-linked immunosorbent assay (ELISA) or passive cutaneous anaphylaxis (PCA) in recipient rats following adoptive transfer. In conclusion, allergic late airway responses (LAR) and cholinergic airway hyperresponsiveness, but not antigen-specific IgE and early responses, were adoptively transferred by antigen-primed lymphocytes in BN rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7599864

  13. Cutaneous antigen priming via gene gun leads to skin-selective Th2 immune-inflammatory responses.

    PubMed

    Alvarez, David; Harder, Greg; Fattouh, Ramzi; Sun, Jiangfeng; Goncharova, Susanna; Stämpfli, Martin R; Coyle, Anthony J; Bramson, Jonathan L; Jordana, Manel

    2005-02-01

    It is becoming increasingly evident that the compartmentalization of immune responses is governed, in part, by tissue-selective homing instructions imprinted during T cell differentiation. In the context of allergic diseases, the fact that "disease" primarily manifests in particular tissue sites, despite pervasive allergen exposure, supports this notion. However, whether the original site of Ag exposure distinctly privileges memory Th2 immune-inflammatory responses to the same site, while sparing remote tissue compartments, remains to be fully investigated. We examined whether skin-targeted delivery of plasmid DNA encoding OVA via gene-gun technology in mice could generate allergic sensitization and give rise to Th2 effector responses in the skin as well as in the lung upon subsequent Ag encounter. Our data show that cutaneous Ag priming induced OVA-specific serum IgE and IgG1, robust Th2-cytokine production, and late-phase cutaneous responses and systemic anaphylactic shock upon skin and systemic Ag recall, respectively. However, repeated respiratory exposure to aerosolized OVA failed to instigate airway inflammatory responses in cutaneous Ag-primed mice, but not in mice initially sensitized to OVA via the respiratory mucosa. Importantly, these contrasting airway memory responses correlated with the occurrence of Th2 differentiation events at anatomically separate sites: indeed cutaneous Ag priming resulted in Ag-specific proliferative responses and Th2 differentiation in skin-, but not thoracic-, draining lymph nodes. These data indicate that Ag exposure to the skin leads to Th2 differentiation within skin-draining lymph nodes and subsequent Th2 immunity that is selectively manifested in the skin. PMID:15661930

  14. Role of breast regression protein-39/YKL-40 in asthma and allergic responses

    PubMed Central

    Elias, Jack A

    2010-01-01

    BRP-39 and its human homolog YKL-40 have been regarded as a prototype of chitinase-like proteins (CLP) in mammals. Exaggerated levels of YKL-40 protein and/or mRNA have been noted in a number of diseases characterized by inflammation, tissue remodeling, and aberrant cell growth. Asthma is an inflammatory disease characterized by airway hyperresponsiveness and airway remodeling. Recently, the novel regulatory role of BRP-39/YKL-40 in the pathogenesis of asthma has been demonstrated both in human studies and allergic animal models. The levels of YKL-40 are increased in the circulation and lungs from asthmatics where they correlate with disease severity, and CHI3L1 polymorphisms correlate with serum YKL-40 levels, asthma and abnormal lung function. Animal studies using BRP-39 null mutant mice demonstrated that BRP-39 was required for optimal allergen sensitization and Th2 inflammation. These studies suggest the potential use of BRP-39 as a biomarker as well as a therapeutic target for asthma and other allergic diseases. Here, we present an overview of chitin/chitinase biology and summarize recent findings on the role of BRP-39 in the pathogenesis of asthma and allergic responses. PMID:20224674

  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. The Rhizomes of Acorus gramineus and the Constituents Inhibit Allergic Response In vitro and In vivo.

    PubMed

    Lim, Hyun; Lee, Seung Young; Lee, Kang Ro; Kim, Yeong Shik; Kim, Hyun Pyo

    2012-09-01

    The rhizomes of Acorus gramineus have frequently been used in traditional medicine mainly for sedation as well as enhancing brain function. In this study, the anti-allergic activity of A. gramineus was investigated. The 70% ethanol extract of the rhizomes of A. gramineus was found to inhibit the allergic response against 5-lipoxygenase (5-LOX)-catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells and β-hexosaminidase release from RBL-2H3 cells with IC50's of 48.9 and >200 μg/ml, respectively. Among the 9 major constituents isolated, β-asarone, (2R,3R,4S,5S)-2,4-dimethyl-1,3-bis (2',4',5'-trimethoxyphenyl)tetrahydrofuran (AF) and 2,3-dihydro-4,5,7-trimethoxy-1-ethyl-2-methyl-3-(2,4,5-trimethoxyphenyl)indene (AI) strongly inhibited 5-LOX-catalyzed LT production in A23187-treated RBL-1 cells, AI being the most potent (IC50=6.7 μM). Against β-hexosaminidase release by antigen-stimulated RBL-2H3 cells, only AI exhibited strong inhibition (IC50=7.3 μM) while β-asarone and AF showed 26.0% and 39.9% inhibition at 50 μM, respectively. In addition, the ethanol extract of A. gramineus showed significant inhibitory action against the hapten-induced delayed hypersensitivity reaction in mice by oral administration at 200 mg/kg. Therefore, it is suggested that A. gramineus possesses anti-allergic activity and the constituents including β-asarone and AI certainly contribute to the anti-allergic activity of the rhizomes of A. gramineus. PMID:24009837

  17. Nitration of β-Lactoglobulin but Not of Ovomucoid Enhances Anaphylactic Responses in Food Allergic Mice

    PubMed Central

    Diesner, Susanne C.; Schultz, Cornelia; Ackaert, Chloé; Oostingh, Gertie J.; Ondracek, Anna; Stremnitzer, Caroline; Singer, Josef; Heiden, Denise; Roth-Walter, Franziska; Fazekas, Judit; Assmann, Vera E.; Jensen-Jarolim, Erika; Stutz, Hanno; Duschl, Albert; Untersmayr, Eva

    2015-01-01

    Background We revealed in previous studies that nitration of food proteins reduces the risk of de novo sensitization in a murine food allergy model. In contrast, in situations with preformed specific IgE antibodies, in vitro experiments suggested an increased capacity of effector cell activation by nitrated food proteins. Objective The aim of this study was to investigate the influence of protein nitration on the effector phase of food allergy. Design BALB/c mice were immunized intraperitoneally (i.p.) with the milk allergen β-lactoglobulin (BLG) or the egg allergen ovomucoid (OVM), followed by intragastric (i.g.) gavages to induce a strong local inflammatory response and allergen-specific antibodies. Subsequently, naïve and allergic mice were intravenously (i.v.) challenged with untreated, sham-nitrated or nitrated BLG or OVM. Anaphylaxis was monitored by measuring core body temperature and determination of mouse mast cell protease-1 (mMCP-1) levels in blood. Results A significant drop of body temperature accompanied with significantly elevated concentrations of the anaphylaxis marker mMCP-1 were only observed in BLG allergic animals challenged with nitrated BLG and not in OVM allergic mice challenged with nitrated OVM. SDS-PAGE and circular dichroism analysis of the differentially modified allergens revealed an effect of nitration on the secondary protein structure exclusively for BLG together with enhanced protein aggregation. Conclusion Our data suggest that nitration affects differently the food allergens BLG and OVM. In the case of BLG, structural changes favored dimerization possibly explaining the increased anaphylactic reactivity in BLG allergic animals. PMID:25955653

  18. 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

  19. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses

    PubMed Central

    Nam, Seon Young; Yang, Kwang Hee; Kim, Cha Soon; Lee, In Kyung; Kim, Ji Young

    2015-01-01

    Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro. PMID:26317642

  20. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    PubMed

    Joo, Hae Mi; Kang, Su Jin; Nam, Seon Young; Yang, Kwang Hee; Kim, Cha Soon; Lee, In Kyung; Kim, Ji Young

    2015-01-01

    Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro. PMID:26317642

  1. Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study.

    PubMed

    Berardesca, E; Barbareschi, M; Veraldi, S; Pimpinelli, N

    2001-11-01

    Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis. PMID:11722487

  2. 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.

  3. A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

    PubMed

    Llop-Guevara, Alba; Chu, Derek K; Walker, Tina D; Goncharova, Susanna; Fattouh, Ramzi; Silver, Jonathan S; Moore, Cheryl Lynn; Xie, Juliana L; O'Byrne, Paul M; Coyle, Anthony J; Kolbeck, Roland; Humbles, Alison A; Stämpfli, Martin R; Jordana, Manel

    2014-01-01

    Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure. Regarding house dust mite (HDM), we previously identified the threshold required to elicit allergic responses in BALB/c mice. Here, we investigated the impact of an initial immune perturbation on the response to sub-threshold HDM exposure. We show that transient GM-CSF expression in the lung facilitated robust eosinophilic inflammation, long-lasting antigen-specific Th2 responses, mucus production and airway hyperresponsiveness. This was associated with increased IL-33 levels and activated CD11b(+) DCs expressing OX40L. GM-CSF-driven allergic responses were significantly blunted in IL-33-deficient mice. IL-33 was localized on alveolar type II cells and in vitro stimulation of human epithelial cells with GM-CSF enhanced intracellular IL-33 independently of IL-1α. Likewise, GM-CSF administration in vivo resulted in increased levels of IL-33 but not IL-1α. These findings suggest that exposures to environmental agents associated with GM-CSF production, including airway infections and pollutants, may decrease the threshold of allergen responsiveness and, hence, increase the susceptibility to develop allergic asthma through a GM-CSF/IL-33/OX40L pathway. PMID:24551140

  4. A GM-CSF/IL-33 Pathway Facilitates Allergic Airway Responses to Sub-Threshold House Dust Mite Exposure

    PubMed Central

    Llop-Guevara, Alba; Chu, Derek K.; Walker, Tina D.; Goncharova, Susanna; Fattouh, Ramzi; Silver, Jonathan S.; Moore, Cheryl Lynn; Xie, Juliana L.; O’Byrne, Paul M.; Coyle, Anthony J.; Kolbeck, Roland; Humbles, Alison A.; Stämpfli, Martin R.; Jordana, Manel

    2014-01-01

    Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure. Regarding house dust mite (HDM), we previously identified the threshold required to elicit allergic responses in BALB/c mice. Here, we investigated the impact of an initial immune perturbation on the response to sub-threshold HDM exposure. We show that transient GM-CSF expression in the lung facilitated robust eosinophilic inflammation, long-lasting antigen-specific Th2 responses, mucus production and airway hyperresponsiveness. This was associated with increased IL-33 levels and activated CD11b+ DCs expressing OX40L. GM-CSF-driven allergic responses were significantly blunted in IL-33-deficient mice. IL-33 was localized on alveolar type II cells and in vitro stimulation of human epithelial cells with GM-CSF enhanced intracellular IL-33 independently of IL-1α. Likewise, GM-CSF administration in vivo resulted in increased levels of IL-33 but not IL-1α. These findings suggest that exposures to environmental agents associated with GM-CSF production, including airway infections and pollutants, may decrease the threshold of allergen responsiveness and, hence, increase the susceptibility to develop allergic asthma through a GM-CSF/IL-33/OX40L pathway. PMID:24551140

  5. Cellular lesion responsible for exaggerated IgE synthesis accompanying allergic breakthrough

    SciTech Connect

    Marcelletti, J.F.; Katz, D.H.

    1989-05-01

    Appropriate levels of IgE are maintained by a cellular and molecular network composed of (1) a suppressive, Ly-1+, CD4+ T cell-dependent arm that is activated by inappropriate high levels of IgE and (2) an enhancing, CD8+ T cell-dependent arm that controls this suppression in a feedback regulatory manner. Ly-1+ T cells also function to counterbalance (inhibit) the activity of these latter CD8+ T cells. It has been previously shown that Ly-1+ T cells can reverse low-dose irradiation-induced enhancement of IgE antibody responses (i.e., allergic breakthrough). We have analyzed lymphocytes isolated from mice subjected to low-dose irradiation to determine which component of this network is defective in such animals. Stimulation of normal lymphocytes with IgE in vitro resulted in the release of lymphokines that suppress IgE antibody responses. In contrast, similar stimulation of lymphocytes from irradiated mice did not elicit secretion of such suppressive lymphokines, unless the cells were depleted of CD8+ T cells or reconstituted with normal Ly-1+ T cells. Because Ly-1+ T cells of irradiated mice could not reconstitute the response, we conclude that this functional subset of CD4+ T cells, which normally controls CD8+ T cell activity in this network, is defective in animals that exhibit irradiation-induced allergic breakthrough.

  6. DNA repair responses in human skin cells

    SciTech Connect

    Hanawalt, P.C.; Liu, S.C.; Parsons, C.S.

    1981-07-01

    Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.

  7. Modulation of the immune response by infection with Cryptosporidium spp. in children with allergic diseases.

    PubMed

    Guangorena-Gómez, J O; Maravilla-Domínguez, A; García-Arenas, G; Cervantes-Flores, M; Meza-Velázquez, R; Rivera-Guillén, M; Acosta-Saavedra, L C; Goytia-Acevedo, R C

    2016-08-01

    It has been demonstrated that the allergic response can be ameliorated by the administration of pathogen derivatives that activate Toll-like receptors and induce a Th1-type immune response (IR). Cryptosporidium is a parasite that promotes an IR via Toll-like receptors and elicits the production of Th1-type cytokines, which limit cryptosporidiosis. The aim of this study was to investigate allergy-related immune markers in children naturally infected with Cryptosporidium. In a cross-sectional study, 49 children with or without clinical diagnosis of allergies, oocysts of Cryptosporidium spp. in the faeces were screened microscopically. We microscopically screened for leucocytes, examined T and B cells for allergy-related activation markers using flow cytometry and evaluated serum for total IgE using chemiluminescence. Children with allergies and Cryptosporidium in the faeces had significantly lower levels of total IgE, B cells, CD19(+) CD23(+) and CD19(+) CD124(+) cells as well as a greater percentage of interferon-gamma (IFN-γ(+) ) and IL-4(+) CD4(+) cells than children with allergies without Cryptosporidium. This is the first description of the modulation of the IR in children with allergic diseases in the setting of natural Cryptosporidium infection. Our findings suggest the involvement of CD4(+) cells producing IL-4 and IFN-γ in the IR to Cryptosporidium in naturally infected children. PMID:27150641

  8. Treatment of allergic asthma: Modulation of Th2 cells and their responses

    PubMed Central

    2011-01-01

    Atopic asthma is a chronic inflammatory pulmonary disease characterised by recurrent episodes of wheezy, laboured breathing with an underlying Th2 cell-mediated inflammatory response in the airways. It is currently treated and, more or less, controlled depending on severity, with bronchodilators e.g. long-acting beta agonists and long-acting muscarinic antagonists or anti-inflammatory drugs such as corticosteroids (inhaled or oral), leukotriene modifiers, theophyline and anti-IgE therapy. Unfortunately, none of these treatments are curative and some asthmatic patients do not respond to intense anti-inflammatory therapies. Additionally, the use of long-term oral steroids has many undesired side effects. For this reason, novel and more effective drugs are needed. In this review, we focus on the CD4+ Th2 cells and their products as targets for the development of new drugs to add to the current armamentarium as adjuncts or as potential stand-alone treatments for allergic asthma. We argue that in early disease, the reduction or elimination of allergen-specific Th2 cells will reduce the consequences of repeated allergic inflammatory responses such as lung remodelling without causing generalised immunosuppression. PMID:21867534

  9. Beta-escin has potent anti-allergic efficacy and reduces allergic airway inflammation

    PubMed Central

    2010-01-01

    Background Type I hypersensitivity is characterized by the overreaction of the immune system against otherwise innocuous substances. It manifests as allergic rhinitis, allergic conjunctivitis, allergic asthma or atopic dermatitis if mast cells are activated in the respective organs. In case of systemic mast cell activation, life-threatening anaphylaxis may occur. Currently, type I hypersensitivities are treated either with glucocorticoids, anti-histamines, or mast cell stabilizers. Although these drugs exert a strong anti-allergic effect, their long-term use may be problematic due to their side-effects. Results In the course of a routine in vitro screening process, we identified beta-escin as a potentially anti-allergic compound. Here we tested beta-escin in two mouse models to confirm this anti-allergic effect in vivo. In a model of the early phase of allergic reactions, the murine passive cutaneous anaphylaxis model, beta-escin inhibited the effects of mast cell activation and degranulation in the skin and dose-dependently prevented the extravasation of fluids into the tissue. Beta-escin also significantly inhibited the late response after antigen challenge in a lung allergy model with ovalbumin-sensitized mice. Allergic airway inflammation was suppressed, which was exemplified by the reduction of leucocytes, eosinophils, IL-5 and IL-13 in the bronchoalveolar lavage fluid. Histopathological examinations further confirmed the reduced inflammation of the lung tissue. In both models, the inhibitory effect of beta-escin was comparable to the benchmark dexamethasone. Conclusions We demonstrated in two independent murine models of type I hypersensitivity that beta-escin has potent anti-allergic properties. These results and the excellent safety profile of beta-escin suggest a therapeutic potential of this compound for a novel treatment of allergic diseases. PMID:20487574

  10. Enhancement of allergic responses in vivo and in vitro by butylated hydroxytoluene

    SciTech Connect

    Yamaki, Kouya; Taneda, Shinji; Yanagisawa, Rie; Inoue, Ken-ichiro; Takano, Hirohisa; Yoshino, Shin

    2007-09-01

    The effect of butylated hydroxytoluene (BHT), which is used widely as an antioxidant, on IgE-dependent allergic responses in vivo and in vitro was investigated. For in vivo study, passive cutaneous anaphylaxis (PCA) was elicited in rats by i.d. injection of anti-DNP IgE and 48 h later by i.v. injection of DNP-HSA. BHT was i.p. given immediately after anti-DNP IgE injection. For in vitro studies, the rat mast cell line RBL2H3 sensitized with monoclonal anti-dinitrophenol (DNP) IgE was challenged with the multivalent antigen DNP-human serum albumin (DNP-HSA) in the presence or absence of BHT. {beta}-Hexosaminidase and histamine released from RBL2H3 cells, as indicators of degranulation of the cells, the concentration of intracellular Ca{sup 2+}, the level of phosphorylated-Akt, and global tyrosine phosphorylation as indicators of mast cell activation, were measured. The results showed that BHT given to anti-DNP IgE-sensitized rats augmented DNP-specific PCA in a dose-dependent manner. In the presence of BHT, IgE-induced releases of {beta}-hexosaminidase and histamine from RBL2H3 cells were increased. BHT also further elevated IgE-mediated increased concentrations of intracellular Ca{sup 2+} and the levels of phosphorylated-Akt, but did not affect global tyrosine phosphorylation, in RBL2H3 cells. Moreover, the PI3K inhibitor LY294002 inhibited IgE-dependent degranulation and its enhancement by BHT. These findings indicate that BHT may upregulate PCA by enhancing mast cell degranulation associated with enhancements of intracellular Ca{sup 2+} concentration and PI3K activation, suggesting that BHT might affect allergic diseases such as allergic rhinitis and asthma.

  11. Allergic Skin Conditions

    MedlinePlus

    American Academy of Allergy Asthma & Immunology Menu Search Main navigation Skip to content Conditions & Treatments Allergies Asthma Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just ...

  12. Responsive corneosurfametry following in vivo skin preconditioning.

    PubMed

    Uhoda, E; Goffin, V; Pierard, G E

    2003-12-01

    Skin is subjected to many environmental threats, some of which altering the structure and function of the stratum corneum. Among them, surfactants are recognized factors that may influence irritant contact dermatitis. The present study was conducted to compare the variations in skin capacitance and corneosurfametry (CSM) reactivity before and after skin exposure to repeated subclinical injuries by 2 hand dishwashing liquids. A forearm immersion test was performed on 30 healthy volunteers. 2 daily soak sessions were performed for 5 days. At inclusion and the day following the last soak session, skin capacitance was measured and cyanoacrylate skin-surface strippings were harvested. The latter specimens were used for the ex vivo microwave CSM. Both types of assessments clearly differentiated the 2 hand dishwashing liquids. The forearm immersion test allowed the discriminant sensitivity of CSM to increase. Intact skin capacitance did not predict CSM data. By contrast, a significant correlation was found between the post-test conductance and the corresponding CSM data. In conclusion, a forearm immersion test under realistic conditions can discriminate the irritation potential between surfactant-based products by measuring skin conductance and performing CSM. In vivo skin preconditioning by surfactants increases CSM sensitivity to the same surfactants. PMID:15025702

  13. Elevated and cross-responsive CD1a-reactive T cells in bee and wasp venom allergic individuals.

    PubMed

    Subramaniam, Sumithra; Aslam, Aamir; Misbah, Siraj A; Salio, Mariolina; Cerundolo, Vincenzo; Moody, D Branch; Ogg, Graham

    2016-01-01

    The role of CD1a-reactive T cells in human allergic disease is unknown. We have previously shown that circulating CD1a-reactive T cells recognize neolipid antigens generated by bee and wasp venom phospholipase, and here tested the hypothesis that venom-responsive CD1a-reactive T cells associate with venom allergy. Circulating T cells from bee and wasp venom allergic individuals, before and during immunotherapy, were exposed to CD1a-transfected K562 cells in the presence of wasp or bee venom. T-cell response was evaluated based on IFNγ, GM-CSF, and IL-13 cytokine production. Venom allergic individuals showed significantly higher frequencies of IFN-γ, GM-CSF, and IL-13 producing CD1a-reactive T cells responsive to venom and venom-derived phospholipase than healthy individuals. Venom-responsive CD1a-reactive T cells were cross-responsive between wasp and bee suggesting shared pathways of allergenicity. Frequencies of CD1a-reactive T cells were initially induced during subcutaneous immunotherapy, peaking by weeks 5, but then reduced despite escalation of antigen dose. Our current understanding of venom allergy and immunotherapy is largely based on peptide and protein-specific T cell and antibody responses. Here, we show that lipid antigens and CD1a-reactive T cells associate with the allergic response. These data have implications for mechanisms of allergy and approaches to immunotherapy. PMID:26518614

  14. Elevated and cross‐responsive CD1a‐reactive T cells in bee and wasp venom allergic individuals

    PubMed Central

    Subramaniam, Sumithra; Aslam, Aamir; Misbah, Siraj A.; Salio, Mariolina; Cerundolo, Vincenzo; Moody, D Branch

    2015-01-01

    The role of CD1a‐reactive T cells in human allergic disease is unknown. We have previously shown that circulating CD1a‐reactive T cells recognize neolipid antigens generated by bee and wasp venom phospholipase, and here tested the hypothesis that venom‐responsive CD1a‐reactive T cells associate with venom allergy. Circulating T cells from bee and wasp venom allergic individuals, before and during immunotherapy, were exposed to CD1a‐transfected K562 cells in the presence of wasp or bee venom. T‐cell response was evaluated based on IFNγ, GM‐CSF, and IL‐13 cytokine production. Venom allergic individuals showed significantly higher frequencies of IFN‐γ, GM‐CSF, and IL‐13 producing CD1a‐reactive T cells responsive to venom and venom‐derived phospholipase than healthy individuals. Venom‐responsive CD1a‐reactive T cells were cross‐responsive between wasp and bee suggesting shared pathways of allergenicity. Frequencies of CD1a‐reactive T cells were initially induced during subcutaneous immunotherapy, peaking by weeks 5, but then reduced despite escalation of antigen dose. Our current understanding of venom allergy and immunotherapy is largely based on peptide and protein‐specific T cell and antibody responses. Here, we show that lipid antigens and CD1a‐reactive T cells associate with the allergic response. These data have implications for mechanisms of allergy and approaches to immunotherapy. PMID:26518614

  15. 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 ...

  16. The framing effect and skin conductance responses

    PubMed Central

    Ring, Patrick

    2015-01-01

    Individuals often rely on simple heuristics when they face complex choice situations under uncertainty. Traditionally, it has been proposed that cognitive processes are the main driver to evaluate different choice options and to finally reach a decision. Growing evidence, however, highlights a strong interrelation between judgment and decision-making (JDM) on the one hand, and emotional processes on the other hand. This also seems to apply to judgmental heuristics, i.e., decision processes that are typically considered to be fast and intuitive. In this study, participants are exposed to different probabilities of receiving an unpleasant electric shock. Information about electric shock probabilities is either positively or negatively framed. Integrated skin conductance responses (ISCRs) while waiting for electric shock realization are used as an indicator for participants' emotional arousal. This measure is compared to objective probabilities. I find evidence for a relation between emotional body reactions measured by ISCRs and the framing effect. Under negative frames, participants show significantly higher ISCRs while waiting for an electric shock to be delivered than under positive frames. This result might contribute to a better understanding of the psychological processes underlying JDM. Further studies are necessary to reveal the causality underlying this finding, i.e., whether emotional processes influence JDM or vice versa. PMID:26300747

  17. Enhanced allergic responsiveness after early childhood infection with respiratory viruses: Are long-lived alternatively activated macrophages the missing link?

    PubMed

    Keegan, Achsah D; Shirey, Kari Ann; Bagdure, Dayanand; Blanco, Jorge; Viscardi, Rose M; Vogel, Stefanie N

    2016-07-01

    Early childhood infection with respiratory viruses, including human rhinovirus, respiratory syncytial virus (RSV) and influenza, is associated with an increased risk of allergic asthma and severe exacerbation of ongoing disease. Despite the long recognition of this relationship, the mechanism linking viral infection and later susceptibility to allergic lung inflammation is still poorly understood. We discuss the literature and provide new evidence demonstrating that these viruses induce the alternative activation of macrophages. Alternatively activated macrophages (AAM) induced by RSV or influenza infection persisted in the lungs of mice up to 90 days after initial viral infection. Several studies suggest that AAM contribute to allergic inflammatory responses, although their mechanism of action is unclear. In this commentary, we propose that virus-induced AAM provide a link between viral infection and enhanced responses to inhaled allergens. PMID:27178560

  18. Basophil response to peanut allergens in Mediterranean peanut-allergic patients.

    PubMed

    Mayorga, C; Gomez, F; Aranda, A; Koppelman, S J; Diaz-Perales, A; Blanca-López, N; Blazquez, A B; Blanca, M; Torres, M J

    2014-07-01

    Ara h 1, Ara h 2, and Ara h 3 are important sensitizers in peanut allergy. Ara h 9 has also been shown to be relevant in the Mediterranean area. We evaluated the basophil response to peanut allergens and Pru p 3 in Mediterranean patients: Group 1, peanut and peach allergy; Group 2, peanut allergy and tolerance to peach; Group 3, peach allergy and tolerance to peanut; Group 4, nonallergic subjects that tolerate both peanut and peach. Compared to controls (Group 4), there was an increased basophil activation with Ara h 2 (P = 0.031) and Pru p 3 (P = 0.009) in Group 1 and with Ara h 1 (P = 0.016), Ara h 2 (P = 0.001), and Ara h 9 (P = 0.016) in Group 2. Importantly, only Ara h 2 showed an increased activation (P = 0.009) in Group 2 compared to Group 3. Ara h 2 is the best discriminating allergen for peanut allergy diagnosis in a Mediterranean population showing two patterns: patients also allergic to peach, responding to Ara h 2 and Pru p 3, and patients allergic only to peanut, responding to Ara h 1, Ara h 2, and Ara h 9. PMID:24816395

  19. Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation

    PubMed Central

    Gobbato, Nathália Brandão; de Souza, Flávia Castro Ribas; Fumagalli, Stella Bruna Napolitano; Lopes, Fernanda Degobbi Tenório Quirino dos Santos; Prado, Carla Máximo; Martins, Milton Arruda; Tibério, Iolanda de Fátima Lopes Calvo; Leick, Edna Aparecida

    2013-01-01

    Aims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-κB, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-κB positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response. PMID:24151607

  20. CARMA1 is necessary for optimal T cell responses in a murine model of allergic asthma.

    PubMed

    Ramadas, Ravisankar A; Roche, Marly I; Moon, James J; Ludwig, Thomas; Xavier, Ramnik J; Medoff, Benjamin D

    2011-12-15

    CARMA1 is a lymphocyte-specific scaffold protein necessary for T cell activation. Deletion of CARMA1 prevents the development of allergic airway inflammation in a mouse model of asthma due to a defect in naive T cell activation. However, it is unknown if CARMA1 is important for effector and memory T cell responses after the initial establishment of inflammation, findings that would be more relevant to asthma therapies targeted to CARMA1. In the current study, we sought to elucidate the role of CARMA1 in T cells that have been previously activated. Using mice in which floxed CARMA1 exons can be selectively deleted in T cells by OX40-driven Cre recombinase (OX40(+/Cre)CARMA1(F/F)), we report that CD4(+) T cells from these mice have impaired T cell reactivation responses and NF-κB signaling in vitro. Furthermore, in an in vivo recall model of allergic airway inflammation that is dependent on memory T cell function, OX40(+/Cre)CARMA1(F/F) mice have attenuated eosinophilic airway inflammation, T cell activation, and Th2 cytokine production. Using MHC class II tetramers, we demonstrate that the development and maintenance of Ag-specific memory T cells is not affected in OX40(+/Cre)CARMA1(F/F) mice. In addition, adoptive transfer of Th2-polarized OX40(+/Cre)CARMA1(F/F) Ag-specific CD4(+) T cells into wild-type mice induces markedly less airway inflammation in response to Ag challenge than transfer of wild-type Th2 cells. These data demonstrate a novel role for CARMA1 in effector and memory T cell responses and suggest that therapeutic strategies targeting CARMA1 could help treat chronic inflammatory disorders such as asthma. PMID:22075698

  1. Orally-Induced Intestinal CD4+ CD25+ FoxP3+ Treg Controlled Undesired Responses towards Oral Antigens and Effectively Dampened Food Allergic Reactions

    PubMed Central

    Smaldini, Paola Lorena; Orsini Delgado, María Lucía; Fossati, Carlos Alberto; Docena, Guillermo Horacio

    2015-01-01

    The induction of peripheral tolerance may constitute a disease-modifying treatment for allergic patients. We studied how oral immunotherapy (OIT) with milk proteins controlled allergy in sensitized mice (cholera toxin plus milk proteins) upon exposure to the allergen. Symptoms were alleviated, skin test was negativized, serum specific IgE and IgG1 were abrogated, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells was observed, while IL-13 gene expression in jejunum was down-regulated, and IL-10 and TGF-β were increased. In addition, we observed an induction of CD4+CD25+FoxP3+ cells and IL-10- and TGF-β-producing regulatory T cells in the lamina propria. Finally, transfer experiments confirmed the central role of these cells in tolerance induction. We demonstrated that the oral administration of milk proteins pre- or post-sensitization controlled the Th2-immune response through the elicitation of mucosal IL-10- and TGF-β-producing Tregs that inhibited hypersensitivity symptoms and the allergic response. PMID:26517875

  2. [Antihistamines in allergic rhinitis].

    PubMed

    Kruszewski, Jerzy

    2007-01-01

    Antihistamines are the first line of pharmacotherapy in allergic diseases, especially in allergic rhinitis. The article also presents the interesting 2005-2007 publications on the use of antihistamine in practical point of view, especially the newly introduced ones (desloratadine, fexofenadine, levocetirizine) and those which are to be introduced soon (rupatadine). The efficacy in skin histamine provocation model and various clinical model were discussed. PMID:18260244

  3. Response to Nonallergenic Irritants in Children With Allergic and Nonallergic Rhinitis

    PubMed Central

    Baek, Ji Hyeon; Cho, Eunhae; Kim, Mi Ae; Lee, Seung Won; Kang, Yu Sun; Sheen, Youn Ho; Jee, Hye Mi; Jung, Young-Ho

    2016-01-01

    Purpose Nonallergenic irritants can aggravate the symptoms of rhinitis. We investigated the clinical responses of children with allergic rhinitis (AR) and nonallergic rhinitis (NAR) to nonallergenic irritants, and identified factors associated with these responses. Methods Children with chronic rhinitis (n=208) were classified as having AR or NAR based on the presence of aeroallergen-specific IgE. Healthy controls (n=24) were recruited for comparison. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines were used to classify patients, and their irritant score (0-21 points) and current symptom score (5-35 points) were measured. Subjects with irritant scores ≥3 and <3 were classified as having irritant and nonirritant rhinitis, respectively. Results The mean age of enrolled subjects was 6.8 years (range: 1.8-16.0 years). The AR and NAR groups had similar irritant scores (P=0.394) and proportions of subjects with irritant scores ≥3 (P=0.105). Irritant score correlated positively with symptom score (P=0.005), and the proportion of subjects with irritant scores ≥3 was greater in children with moderate-severe rhinitis than in those with mild rhinitis (P=0.046). Multiple logistic regression analysis indicated that the presence of atopic eczema increased the risk for sensitivity to a nonallergenic irritant (aOR=2.928, 95% CI 1.567-5.473, P=0.001). Conclusions Response to a nonallergenic irritant was useful for gauging the severity of rhinitis, but not for differentiating AR from NAR. AR and NAR patients with atopic eczema may increase nasal sensitivity to nonallergenic irritants. PMID:27126728

  4. Mediator profiles in tears during the conjunctival response induced by allergic reaction in the nasal mucosa

    PubMed Central

    2013-01-01

    Background The allergic reaction occurring primarily in the nasal mucosa can induce a secondary conjunctival response of an immediate (SICR), late (SLCR), or delayed (SDYCR) type in some patients with allergic conjunctivitis (AC). Objectives To investigate the concentration changes of histamine, tryptase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), leukotrienes (LTB 4, LTC4, LTE4), myeloperoxidase (MPO), interferon-γ (IFN-γ), and interleukins (IL-2, IL-4, IL-5) in tears during the SICR, SLCR, and SDYCR. Methods In 32 patients with AC, 11 SICR (p<0.01), 13 SLCR (p<0.001), and eight SDYCR (p<0.01) to nasal challenges with allergens (NPTs), the NPTs and 32 control tests with PBS were repeated and supplemented with the determination of these factors in tears. Results The SICRs were associated with significant concentration changes in tears (p<0.05) of histamine, tryptase, ECP, LTC4, and IL-4. The SLCRs were accompanied by significant changes in concentrations of histamine, ECP, LTB4, LTC4, MPO, IL-4, and IL-5. The SDYCRs were associated with significant concentration changes in tears (p<0.05) of LTB4, MPO, IFN-γ, and IL-2. No significant changes in these factors were recorded in tears during the 32 PBS controls (p>0.1) or in the ten control patients (p>0.1). Conclusions These results provide evidence for causal involvement of nasal allergy in some patients with AC, inducing secondary conjunctival response of immediate (SICR), late SLCR, or delayed SDYCR type, associated with different mediator, cytokine, and cellular profiles in the tears, suggesting involvement of different hypersensitivity mechanisms. These results also emphasize the diagnostic value of nasal allergen challenge combined with monitoring of the conjunctival response in some patients with AC. PMID:23869165

  5. The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells.

    PubMed

    Tsai, Shih Han; Kinoshita, Makoto; Kusu, Takashi; Kayama, Hisako; Okumura, Ryu; Ikeda, Kayo; Shimada, Yosuke; Takeda, Akira; Yoshikawa, Soichiro; Obata-Ninomiya, Kazushige; Kurashima, Yosuke; Sato, Shintaro; Umemoto, Eiji; Kiyono, Hiroshi; Karasuyama, Hajime; Takeda, Kiyoshi

    2015-02-17

    Crosslinking of the immunoglobulin receptor FcεRI activates basophils and mast cells to induce immediate and chronic allergic inflammation. However, it remains unclear how the chronic allergic inflammation is regulated. Here, we showed that ecto-nucleotide pyrophosphatase-phosphodiesterase 3 (E-NPP3), also known as CD203c, rapidly induced by FcεRI crosslinking, negatively regulated chronic allergic inflammation. Basophil and mast cell numbers increased in Enpp3(-/-) mice with augmented serum ATP concentrations. Enpp3(-/-) mice were highly sensitive to chronic allergic pathologies, which was reduced by ATP blockade. FcεRI crosslinking induced ATP secretion from basophils and mast cells, and ATP activated both cells. ATP clearance was impaired in Enpp3(-/-) cells. Enpp3(-/-)P2rx7(-/-) mice showed decreased responses to FcεRI crosslinking. Thus, ATP released by FcεRI crosslinking stimulates basophils and mast cells for further activation causing allergic inflammation. E-NPP3 decreases ATP concentration and suppresses basophil and mast cell activity. PMID:25692702

  6. Improved detection of allergen-specific T-cell responses in allergic contact dermatitis through the addition of 'cytokine cocktails'.

    PubMed

    Moed, Helen; von Blomberg, Mary; Bruynzeel, Derk P; Scheper, Rik; Gibbs, Susan; Rustemeyer, Thomas

    2005-08-01

    The gold standard for the diagnosis of allergic hypersensitivity is skin patch testing with the suspected allergens. This diagnostic tool, however, has distinct disadvantages, and therefore the development of alternative or complementary in vitro tests is of great importance. In this study, we evaluate the applicability of an in vitro test method, as developed earlier for nickel allergy, to detect allergen-specific T cells in the blood of patients allergic to frequent sensitizers (chromate, cobalt, paraphenylenediamine, fragrances and chloromethyl-isothiazolinone). Peripheral blood mononuclear cells (PBMCs) of allergic patients and healthy controls were cultured in the absence or presence of allergen. Additionally, type 1 (IL-7 and IL-12) or type 2 (IL-7 and IL-4) stimulating cytokines were added; after 6-day proliferation, IFN-gamma and IL-5 secretions were determined. Without the addition of cytokines, consistent allergen-induced proliferation was observed in PBMCs of nickel-allergic patients only. By contrast, the addition of type 1 or type 2 stimulating cytokines resulted in a significantly enhanced allergen-specific proliferation for all allergens tested (sensitivity increased from 26 to 43% or 38%, respectively, P < 0.05). In these cultures, allergen-induced IFN-gamma and IL-5 secretion was also significantly increased, compared to healthy controls (P < 0.05, for IFN-gamma sensitivity 79%, specificity 93%; for IL-5 sensitivity 74%, specificity 81%). In conclusion, these results demonstrate an increased proliferative capacity and cytokine production by allergen-specific T cells from allergic patients, but not of healthy individuals upon stimulation with allergens in combination with type 1 or 2 skewing cytokines. The present data warrant further exploration of the application of this test to a broader set of allergens. PMID:16026586

  7. 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...

  8. EFFECTS OF ULTRAVIOLET RADIATION (UVR) ON THE RESPIRATORY ALLERGIC RESPONSES OF BALB/C MICE TO A FUNGAL ALLERGEN

    EPA Science Inventory

    EFFECTS OF ULTRAVIOLET RADIATION (UVR) ON THE RESPIRATORY ALLERGIC RESPONSES OF BALB/C MICE TO A FUNGAL ALLERGEN. M D W Ward, D M Sailstad, D L Andrews, E H Boykin, and MJ K Selgrade. National Health and Environmental Effects Research Laboratory, Office of Research and Developmen...

  9. RESPIRATORY PHYSIOLOGICAL AND ALLERGIC-TYPE RESPONSES TO AN EXTRACT OF STACHYBOTRYS CHARTARUM IN BALB/C MICE

    EPA Science Inventory

    RESPIRATORY PHYSIOLOGICAL AND ALLERGIC-TYPE RESPONSES TO AN EXTRACT OF Stachybotrys chartarum IN BALB/C MICE. ME Viana1, N Haykal-Coates2, S H Gavett2, MJ Selgrade2, and M D W Ward2. 1APR/CVM, NCSU, Raleigh, NC, USA. 2NHEERL, ORD, US EPA, RTP, NC, USA.
    Rationale: assess the ab...

  10. Blunted HPA axis responsiveness to stress in atopic patients is associated with the acuity and severeness of allergic inflammation.

    PubMed

    Buske-Kirschbaum, A; Ebrecht, M; Hellhammer, D H

    2010-11-01

    Previously we could demonstrate attenuated responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to stress in patients with chronic allergic inflammatory disease (i.e., atopic dermatitis, allergic asthma). The present study was designed to investigate HPA axis function in an acute manifestation of allergy. Patients with seasonal allergic rhinitis (SAR; n = 20) and non-atopic controls (n = 20) were exposed to a standardized laboratory stressor ('Trier Social Stress Test'; TSST). Cortisol responses to the TSST and cortisol awakening responses (CAR) were measured in SAR subjects while suffering from acute symptoms of SAR (pollen season), and during a non-active state of their disease (pollen-free season). To assess the acuity and severity of SAR, eosinophil and basophil numbers and SAR symptomatology were determined. Non-allergic control subjects were examined at identical times during the year. To control for possible sequence effects, a cross-over design was used. SAR patients showed significantly increased symptom severity (t = 9.4; p<.001) as well as eosinophil (F(1,31) = 9.8; p<.01) and basophil (F(1,38) = 6.4; p<.05) numbers during the pollen season when compared to a pollen-free period. When exposed to the TSST, significantly attenuated cortisol responses were found in SAR subjects during acute manifestation of the disease (pollen season) when compared to the pollen-free season (F(16,456) = 1.65; p<.05). In SAR patients, there was a significant negative correlation between symptom severity and the cortisol response to the stressor (r = .53; p<.05). No significant between-group or between-condition differences with respect to the CAR could be determined (all p>.05). These findings support previous data of attenuated HPA axis responsiveness to stress in atopic conditions and further, suggest that HPA axis hyporesponsiveness in atopy may be linked to the severity of the allergic inflammatory process. PMID:20633637

  11. Brief analysis of causes of sensitive skin and advances in evaluation of anti-allergic activity of cosmetic products.

    PubMed

    Fan, L; He, C; Jiang, L; Bi, Y; Dong, Y; Jia, Y

    2016-04-01

    This review focuses on the causes of sensitive skin and elaborates on the relationship between skin sensitivity and skin irritations and allergies, which has puzzled cosmetologists. Here, an overview is presented of the research on active ingredients in cosmetic products for sensitive skin (anti-sensitive ingredients), which is followed by a discussion of their experimental efficacy. Moreover, several evaluation methods for the efficacy of anti-sensitive ingredients are classified and summarized. Through this review, we aim to provide the cosmetic industry with a better understanding of sensitive skin, which could in turn provide some theoretical guidance to the research on targeted cosmetic products. PMID:26444676

  12. Superficial Immunity: Antimicrobial Responses Are More Than Skin Deep.

    PubMed

    Mack, Madison R; Kim, Brian S

    2016-07-19

    The skin barrier is essential for host defense, but how the skin provides protection when the barrier is breached is not well understood. In this issue of Immunity, Gallo and colleagues report that keratinocytes integrate signals from antimicrobial peptides via MAVS signaling to amplify their antiviral immune response. PMID:27438760

  13. Intranasal mite allergen induces allergic asthma-like responses in NC/Nga mice.

    PubMed

    Shibamori, Masafumi; Ogino, Keiki; Kambayashi, Yasuhiro; Ishiyama, Hironobu

    2006-01-25

    Airway responses induced by intranasal administration of mite allergen without adjuvant were studied in NC/Nga mice. A crude extract of Dermatophagoides farinae (Df) was administered for 5 consecutive days and a single intranasal challenge booster dose was given 1 week after the last sensitization. 24 h after the single challenge, the airway hyperresponsiveness (AHR) was measured and the bronchoalveolar lavage fluid (BALF) was analyzed for numbers of eosinophils and neutrophils, and both cytokine and chemokine levels. There were marked increases in number of eosinophils in the BALF, AHR, Th2 cytokines (IL-5 and IL-13), and chemokine (eotaxin-1 and eotaxin-2) levels in the BALF following Df exposure. C57BL/6N, A/J, BALB/c, and CBA/JN mouse strains were also exposed to Df crude extract, but all of the measured responses were strongest in NC/Nga mice. Furthermore, Df-exposed NC/Nga mice showed the goblet cell hyperplasia, pulmonary eosinophilic inflammation, and increases in both total serum IgE and Df-specific IgG1. After intranasal exposure of NC/Nga mice to crude extract of Dermatophagoides pteronyssinus, the BALF eosinophilia and AHR were similar to responses induced by Df. None of the study parameters were increased in response to intranasal exposure to ovalbumin. These data demonstrated that NC/Nga mice developed allergic asthma-like responses after intranasal exposure to mite allergens. PMID:16229861

  14. Modulation of peanut-induced allergic immune responses by oral lactic acid bacteria-based vaccines in mice.

    PubMed

    Ren, Chengcheng; Zhang, Qiuxiang; Wang, Gang; Ai, Chunqing; Hu, Mengsha; Liu, Xiaoming; Tian, Fengwei; Zhao, Jianxin; Chen, Yongquan; Wang, Miao; Zhang, Hao; Chen, Wei

    2014-01-01

    Peanut allergy (PNA) has becoming a non-negligible health concern worldwide. Thus far, allergen-specific immunotherapy aimed at inducing mucosal tolerance has widely been regarded as a major management strategy for PNA. The safety profiles and the intrinsic probiotic properties of lactic acid bacteria (LAB) render them attractive delivery vehicles for mucosal vaccines. In the present study, we exploited genetically modified Lactococcus lactis to produce peanut allergen Ara h 2 via different protein-targeting systems and their immunomodulatory potency for allergic immune responses in mice were investigated. By comparison with the strain expressing the cytoplasmic form of Ara h 2 (LL1), the strains expressing the secreted and anchored forms of Ara h 2 (LL2 and LL3) were more potent in redirecting a Th2-polarized to a non-allergic Th1 immune responses. Induction of SIgA and regulatory T cells were also observed at the local levels by orally administration of recombinant L. lactis. Our results indicate that allergen-producing L. lactis strains modulated allergic immune responses and may be developed as promising mucosal vaccines for managing allergic diseases. PMID:24770368

  15. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis

    PubMed Central

    Cosgrove, Sallie B; Wren, Jody A; Cleaver, Dawn M; Martin, David D; Walsh, Kelly F; Harfst, Jessica A; Follis, Stacey L; King, Vickie L; Boucher, Joseph F; Stegemann, Michael R

    2013-01-01

    Background Oclacitinib (Apoquel®) inhibits the function of a variety of pro-inflammatory, pro-allergic and pruritogenic cytokines that are dependent on Janus kinase enzyme activity. Oclacitinib selectively inhibits Janus kinase 1. Hypothesis/Objectives We aimed to evaluate the safety and efficacy of oclacitinib for the control of pruritus associated with allergic dermatitis in a randomized, double-blinded, placebo-controlled trial. Methods Client-owned dogs (n = 436) with moderate to severe owner-assessed pruritus and a presumptive diagnosis of allergic dermatitis were enrolled. Dogs were randomized to either oclacitinib at 0.4–0.6 mg/kg orally twice daily or an excipient-matched placebo. An enhanced 10 cm visual analog scale (VAS) was used by the owners to assess the severity of pruritus from day 0 to 7 and by veterinarians to assess the severity of dermatitis on days 0 and 7. Dogs could remain on the study for 28 days. Results Pretreatment owner and veterinary VAS scores were similar for the two treatment groups. Oclacitinib produced a rapid onset of efficacy within 24 h. Mean oclacitinib Owner Pruritus VAS scores were significantly better than placebo scores (P < 0.0001) on each assessment day. Pruritus scores decreased from 7.58 to 2.59 cm following oclacitinib treatment. The day 7 mean oclacitinib Veterinarian Dermatitis VAS scores were also significantly better (P < 0.0001) than placebo scores. Diarrhoea and vomiting were reported with similar frequency in both groups. Conclusions and clinical importance In this study, oclacitinib provided rapid, effective and safe control of pruritus associated with allergic dermatitis, with owners and veterinarians noting substantial improvements in pruritus and dermatitis VAS scores. PMID:23829933

  16. Designing skin response meter for psycho galvanic reflex

    NASA Astrophysics Data System (ADS)

    Dhokalia, Dhruv M.; Atreya, Parul; Kumar, Arun

    2011-12-01

    Human skin offers some resistance to current and voltage. This resistance changes with the emotional state of the body. The circuit proposed here measures changes in our skin resistance following changes in our mental state. In the relaxed state, the resistance offered by the skin is as high as 2 mega-ohms or more, which reduces to 500 kilo-ohms or less when the emotional stress is too high. The reduction in skin resistance is related to increased blood flow and permeability followed by the physiological changes during high stress. This increases the electrical conductivity of the skin. This circuit is useful to monitor the skin's response to relaxation techniques. It is very sensitive and shows response during a sudden moment of stress. Even a deep sigh will give response in the circuit. The circuit uses a sensitive amplifier to sense variations in the skin resistance. IC CA3140 is designed as a resistance- to-voltage converter that outputs varying voltage based on the skin's conductivity.

  17. The immunomodulatory actions of prostaglandin E2 on allergic airway responses in the rat.

    PubMed

    Martin, James G; Suzuki, Masaru; Maghni, Karim; Pantano, Rosa; Ramos-Barbón, David; Ihaku, Daizo; Nantel, François; Denis, Danielle; Hamid, Qutayba; Powell, William S

    2002-10-01

    PGE(2) has been reported to inhibit allergen-induced airway responses in sensitized human subjects. The aim of this study was to investigate the mechanism of anti-inflammatory actions of PGE(2) in an animal model of allergic asthma. BN rats were sensitized to OVA using Bordetella pertussis as an adjuvant. One week later, an aerosol of OVA was administered. After a further week, animals were anesthetized with urethan, intubated, and subjected to measurements of pulmonary resistance (R(L)) for a period of 8 h after OVA challenge. PGE(2) (1 and 3 micro g in 100 micro l of saline) was administered by insufflation intratracheally 30 min before OVA challenge. The early response was inhibited by PGE(2) (3 micro g). The late response was inhibited by both PGE(2) (1 and 3 micro g). Bronchoalveolar lavage fluid from OVA-challenged rats showed eosinophilia and an increase in the number of cells expressing IL-4 and IL-5 mRNA. These responses were inhibited by PGE(2). Bronchoalveolar lavage fluid levels of cysteinyl-leukotrienes were elevated after OVA challenge and were reduced after PGE(2) to levels comparable with those of sham challenged animals. We conclude that PGE(2) is a potent anti-inflammatory agent that may act by reducing allergen-induced Th2 cell activation and cysteinyl-leukotriene synthesis in the rat. PMID:12244197

  18. Sensitization to cereals and peanut evidenced by skin prick test and specific IgE in food-tolerant, grass pollen allergic patients

    PubMed Central

    2011-01-01

    Background The botanical relation between grass and cereal grains may be relevant when diagnosing food allergy to cereals. The aim was to investigate the diagnostic specificity of skin prick test (SPT) and specific immunoglobulin E (sIgE) tests to cereals and peanut in grass pollen allergic subjects without history of, and clinically reactions to foods botanically related to grass. Methods 70 subjects (41 females; mean age 32 years) and 20 healthy controls (13 females; mean age 24 years) were tested by open food challenge (OFC) with cereals and peanut. SPT and sIgE both with Immulite® (Siemens) and ImmunoCAP® (Phadia) to grass and birch pollen, cereals, peanut and bromelain were performed. Results Of the 65 OFC-negative subjects 29-46% (SPT, depending on cut-off), 20% (Immulite) and 38% (ImmunoCAP) had positive results to one or more of the foods tested. Controls were negative in all tests. Cross-reactive carbohydrate determinants (CCD) as evidenced by reaction to bromelain could explain only a minority of the measured IgE-sensitizations. Conclusion Grass pollen allergic patients with documented food tolerance to cereals and peanut may express significant sensitization. False-positive cereal or peanut allergy diagnoses may be a quantitatively important problem both in routine clinical work and epidemiological studies. PMID:22409998

  19. CROSS REACTIVITY IN ALLERGIC ASTHMA-LIKE RESPONSES BETWEEN MOLD AND HOUSE DUST MITE IN MICE

    EPA Science Inventory

    Molds are ubiquitous in the environment and exposures to molds contribute to various human diseases including allergic asthma. Some mold allergens have been implicated as the causal agent for allergic asthma. Western blot analysis demonstrated IgE-binding cross-reactivity among m...

  20. ALLERGIC RESPONSE TO PLATINUM AND PALLADIUM COMPLEXES DETERMINATION OF NO-EFFECT LEVEL

    EPA Science Inventory

    Rabbits, guinea pigs and mice were subcutaneously injected with PtSO4 (with and without NH4Cl) and PdSO4 (with and without NH4Cl) in an attempt to sensitize the animals to platinum or palladium. No allergic induction was found. No allergic induction to platinum or palladium was f...

  1. Severe systemic allergic reaction induced by accidental skin contact with cow milk in a 16-year-old boy. A case report.

    PubMed

    Liccardi, G; De Falco, F; Gilder, J A; D'Amato, M; D'Amato, G

    2004-01-01

    The symptoms of food allergy are rarely induced by skin contact. A 16-year-old boy was referred to our Allergology Centre after an episode of systemic symptoms triggered by accidental skin contact with a drop of cow milk (CM) dripped from a sandwich containing fresh cheese. The patient had been allergic to CM from the age of 24 months and had experienced several episodes of urticaria-angioedema after the ingestion of tiny or "hidden" amounts of CM proteins. In vivo and in vitro diagnostic procedures showed intense sensitisation to all CM proteins (1/100 dilutions of allergenic extracts produced large wheals, and class 4 specific IgE antibodies. Total IgE antibodies were elevate (770.0 UI/). A moderate degree of bronchial hyperresponsiveness was found (PC20 metacholine: 3.90 milligrams). This case report suggests that patients with a high degree of sensitisation to CM proteins should be alert to the danger of skin contact and should beware of "hidden" CM allergens. PMID:15301310

  2. Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.

    PubMed

    Millien, Valentine Ongeri; Lu, Wen; Shaw, Joanne; Yuan, Xiaoyi; Mak, Garbo; Roberts, Luz; Song, Li-Zhen; Knight, J Morgan; Creighton, Chad J; Luong, Amber; Kheradmand, Farrah; Corry, David B

    2013-08-16

    Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are essential for expression of allergic inflammation and diseases such as asthma. A mechanism that links these inflammatory mediators is essential for explaining the fundamental basis of allergic disease but has been elusive. Here, we demonstrate that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages. Thus, allergic airway inflammation represents an antifungal defensive strategy that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify the molecular basis of allergic disease and suggest new therapeutic strategies. PMID:23950537

  3. Irritancy and allergic responses induced by topical application of ortho-phthalaldehyde.

    PubMed

    Anderson, Stacey E; Umbright, Christina; Sellamuthu, Rajendran; Fluharty, Kara; Kashon, Michael; Franko, Jennifer; Jackson, Laurel G; Johnson, Victor J; Joseph, Pius

    2010-06-01

    Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG(1). In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde. PMID:20176622

  4. Response of human skin to esthetic scarification.

    PubMed

    Gabriel, Vincent A; McClellan, Elizabeth A; Scheuermann, Richard H

    2014-11-01

    This study was undertaken to investigate changes in RNA expression in previously healthy adult human skin following thermal injury induced by contact with hot metal that was undertaken as part of esthetic scarification, a body modification practice. Subjects were recruited to have pre-injury skin and serial wound biopsies performed. 4 mm punch biopsies were taken prior to branding and 1 h, 1 week, and 1, 2 and 3 months after injury. RNA was extracted and quality assured prior to the use of a whole-genome based bead array platform to describe expression changes in the samples using the pre-injury skin as a comparator. Analysis of the array data was performed using k-means clustering and a hypergeometric probability distribution without replacement and corrections for multiple comparisons were done. Confirmatory q-PCR was performed. Using a k of 10, several clusters of genes were shown to co-cluster together based on Gene Ontology classification with probabilities unlikely to occur by chance alone. OF particular interest were clusters relating to cell cycle, proteinaceous extracellular matrix and keratinization. Given the consistent expression changes at 1 week following injury in the cell cycle cluster, there is an opportunity to intervene early following burn injury to influence scar development. PMID:24582755

  5. 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

  6. Effect of raw milk on allergic responses in a murine model of gastrointestinal allergy.

    PubMed

    Hodgkinson, Alison J; McDonald, Natalie A; Hine, Brad

    2014-08-14

    Epidemiological studies have shown an association between the consumption of raw farm milk and reduced incidence of allergy. In the present study, we fed untreated raw milk, gamma-sterilised milk, heat-treated milk or water to mice and compared their responses to allergen exposure and challenge treatment in a mouse model of gastrointestinal allergy. From weaning (3 weeks old), groups of BALB/c female mice (n 8) received raw milk, gamma-sterilised milk, heated milk or water via drink bottles, with the control group receiving water. All mice were fed a standard (dairy protein-free) rodent diet. At 6 and 8 weeks, groups were given intra-peritoneal injections with ovalbumin (OVA)/alum to sensitise them to the antigen. Controls were sham immunised. At week 10, mice were fasted and challenged four times on alternate days by intra-gastric administration with 50 mg OVA or saline. Levels of bacteria and milk proteins were assessed in milk samples. Mouse serum levels of specific IgE, IgG1 and IgG2a antibodies and mouse mast cell protease-1 (MMCP-1) were determined. Cytokine responses to 48 h activation with OVA were measured in cultured splenocytes from mice. Sterilised and heated milks contained no viable bacteria and reduced detectable levels of many milk proteins, in contrast to raw milk. Mice drinking raw milk had highest serum MMCP-1 and specific-OVA IgE responses. Cultured splenocytes from OVA-primed mice produced similar levels of IL-4 in response to the antigen; however, IL-10 levels were highest from mice drinking raw milk. Overall, the present study adds to the evidence that consuming different types of milk can affect allergic responses to a non-related dietary antigen. PMID:24870507

  7. 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 ...

  8. Diesel Exhaust Exposure and Nasal Response to Attenuated Influenza in Normal and Allergic Volunteers

    EPA Science Inventory

    Rationale: Diesel exhaust enhances allergic inflammation, and pollutants are associated with heightened susceptibility to viral respiratory infections. The effects of combined diesel and virus exposure in humans are unknown. Objective: Test whether acute exposure to diesel modif...

  9. Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell–mediated allergic response

    PubMed Central

    Zheng, Mingzhu; Qiu, Yuanjun; Guo, Chuansheng; Ji, Jian; Lei, Lei; Zhang, Xue; Liang, Jingjing; Lou, Jun; Huang, Wei; Dong, Bowen; Wu, Songquan; Wang, Jianli; Ke, Yuehai; Cao, Xuetao; Zhou, Yi Ting

    2014-01-01

    Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. We show that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation via FcεRI. Mice lacking Tespa1 also displayed increased sensitivity to IgE-mediated allergic responses. The dysregulated signaling in KO mast cells was associated with increased activation of Grb2-PLC-γ1-SLP-76 signaling within the LAT1 (linker for activation of T cells family, member 1) signalosome versus the LAT2 signalosome. Collectively, these findings show that Tespa1 orchestrates mast cell activation by tuning the balance of LAT1 and LAT2 signalosome assembly. PMID:25422497

  10. Bathing Effects of Various Seawaters on Allergic (Atopic) Dermatitis-Like Skin Lesions Induced by 2,4-Dinitrochlorobenzene in Hairless Mice

    PubMed Central

    Kim, Choong Gon; Kang, Meehye; Lee, Youn-Ho; Min, Won Gi; Kim, Yong Hwan; Kang, Su Jin; Song, Chang Hyun; Park, Soo Jin; Park, Ji Ha; Han, Chang Hyun; Lee, Young Joon; Ku, Sae Kwang

    2015-01-01

    We evaluated the preventive effects of four types of seawater collected in Republic of Korea on hairless mice with 2,4-dinitrochlorobenzene- (DNCB-) induced allergic/atopic dermatitis (AD). The anti-inflammatory effects were evaluated by measuring tumor necrosis factor- (TNF-) α and interleukins (ILs). Glutathione (GSH), malondialdehyde (MDA), superoxide anion, and inducible nitric oxide synthase (iNOS) were measured to evaluate the antioxidant effects. Caspase-3 and poly (ADP-ribose) polymerase (PARP) were observed to measure the antiapoptotic effects; matrix metalloproteinase- (MMP-) 9 levels were also evaluated. Mice with AD had markedly higher clinical skin severity scores and scratching behaviors; higher TNF-α and ILs (1β, 10, 4, 5, and 13) levels; higher MDA, superoxide anion, caspase-3, PARP, and MMP-9 levels; and greater iNOS activity. However, the severity of AD was significantly decreased by bathing in seawaters, but it did not influence the dermal collagen depositions and skin tissue antioxidant defense systems. These results suggest that bathing in all four seawaters has protective effects against DNCB-induced AD through their favorable systemic and local immunomodulatory effects, active cytoprotective antiapoptotic effects, inhibitory effects of MMP activity and anti-inflammatory and antioxidative effects. PMID:26221169

  11. 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.

    1987-01-01

    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 between baseline nonspecific airway reactivity and changes in lung function and respiratory symptoms following ozone exposure.

  12. Antibody response to low-molecular-weight antigens of Aspergillus fumigatus in allergic bronchopulmonary aspergillosis.

    PubMed Central

    Kurup, V P; Greenberger, P A; Fink, J N

    1989-01-01

    Sera from patients with allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma and normal sera were analyzed for specific antibodies by Western (immuno-) blotting with Aspergillus fumigatus antigens transferred electrophoretically onto polyvinylidene difluoride membranes. Western blot analysis demonstrated consistent reactivity of low-molecular-weight A. fumigatus antigens against ABPA sera but not against uncomplicated aspergilloma or normal sera. None of these low-molecular-weight components had any lectin-binding activity. Sera from patients with aspergilloma, however, frequently reacted with high-molecular-weight components of A. fumigatus. The majority of these high-molecular-weight antigenic components demonstrated concanavalin A-binding activity. The low-molecular-weight bands were discernible in Western blots with sera from all ABPA patients irrespective of disease activities, such as relapse, flare, or treatment. Antibodies detected by methods such as immunodiffusion or enzyme-linked immunosorbent assays demonstrated total antibody responses to most or all antigenic components, while Western blots demonstrated the reactivities of the individual components with the specific antibodies. Western blot analysis thus provided more information for immunodiagnosis of ABPA than other methods, especially when only crude antigens were available. Images PMID:2666440

  13. Exposure to Triclosan Augments the Allergic Response to Ovalbumin in a Mouse Model of Asthma

    PubMed Central

    Anderson, Stacey E.; Franko, Jennifer; Kashon, Michael L.; Anderson, Katie L.; Hubbs, Ann F.; Lukomska, Ewa; Meade, B. Jean

    2015-01-01

    During the last decade, there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouthwashes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75 to 3% (0.375–1.5 mg/mouse/day) for 28 consecutive days. Concordantly, mice were ip injected with OVA (0.9 μg) and aluminum hydroxide (0.5 mg) on days 1 and 10 and challenged with OVA (125 μg) by pharyngeal aspiration on days 19 and 27. Compared with the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, interleukin-13 cytokine levels, and numbers of lung eosinophils were demonstrated when mice were coexposed to OVA and triclosan. Statistically significant increases in OVA-specific and nonspecific airway hyperreactivity were observed for all triclosan coexposed groups compared with the vehicle and OVA controls. In these studies, exposure to triclosan alone was not demonstrated to be allergenic; however, coexposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens. PMID:23192912

  14. Exposure to triclosan augments the allergic response to ovalbumin in a mouse model of asthma.

    PubMed

    Anderson, Stacey E; Franko, Jennifer; Kashon, Michael L; Anderson, Katie L; Hubbs, Ann F; Lukomska, Ewa; Meade, B Jean

    2013-03-01

    During the last decade, there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouthwashes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75 to 3% (0.375-1.5mg/mouse/day) for 28 consecutive days. Concordantly, mice were ip injected with OVA (0.9 µg) and aluminum hydroxide (0.5mg) on days 1 and 10 and challenged with OVA (125 µg) by pharyngeal aspiration on days 19 and 27. Compared with the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, interleukin-13 cytokine levels, and numbers of lung eosinophils were demonstrated when mice were coexposed to OVA and triclosan. Statistically significant increases in OVA-specific and nonspecific airway hyperreactivity were observed for all triclosan coexposed groups compared with the vehicle and OVA controls. In these studies, exposure to triclosan alone was not demonstrated to be allergenic; however, coexposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens. PMID:23192912

  15. Allergic host defences.

    PubMed

    Palm, Noah W; Rosenstein, Rachel K; Medzhitov, Ruslan

    2012-04-26

    Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macroparasites. Here we present arguments to suggest that allergic immunity has an important role in host defence against noxious environmental substances, including venoms, haematophagous 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

  16. Reproducibility of the vascular response to heating in human skin.

    PubMed

    Savage, M V; Brengelmann, G L

    1994-04-01

    Blood flow in human skin increases enormously in response to direct heating. If local skin temperature is held above 42 degrees C, blood flow eventually stabilizes at a level beyond which other influences, barring change in blood pressure, can produce no further increase. If this maximal level is a reproducible characteristic of an individual's cutaneous vasculature, it could be useful in comparing individuals; for example, in their response to hyperthermia. Our experiments were carried out to discover whether the maximal response of the vasculature of the skin of the forearm can be reproduced within reasonable limits and, also, to clarify the time course of the response. We used water sprayed over the surface of the forearms of 10 subjects to hold skin temperature above 42 degrees C for 60 min. During the last 10 min of heating, forearm blood flow (via venous occlusion plethysmography) was stable, at a level ranging from 16 to 38 ml.min-1.100 ml-1. This level, normalized to a blood pressure of 100 mmHg, was reproduced in a given individual on four or five occasions, with an average coefficient of variation of 10%. The response was 77 +/- 11% (SD) complete after 20 min of heating. Elapsed time at 90% of the final value was 35 +/- 9 (SD) min. We conclude that the maximal forearm blood flow response to local heating is a reproducible characteristic of the cutaneous vasculature with potential utility in the scaling of responses between and within individuals. PMID:8045857

  17. 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

  18. 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

  19. Comparative responses to nasal allergen challenge in allergic rhinitic subjects with or without asthma

    PubMed Central

    2011-01-01

    Background Nasal allergen challenge (NAC) is useful to study the pathophysiology of rhinitis, and multiple challenges may more adequately approximate natural exposure. Objective To determine the effect of 4 consecutive daily NAC, on clinical and inflammatory parameters in rhinitics with or without asthma. Methods Rhinitic subjects were recruited: 19 with mild asthma and 13 without asthma. Subjects underwent a control challenge (normal saline) followed by 4 consecutive daily NAC. Allergen challenge consisted of spraying the chosen allergen extract into each nostril until a positive nasal response occurred. Symptoms were recorded on a Likert scale, and oral peak expiratory and nasal peak inspiratory flows allowed assessment of a nasal blockage index (NBI), for a period of 7 hours. Induced sputum and nasal lavage were performed on control day and after 1 and 4 days of NAC. Results Compared with the control day, there was a significant increase in symptom scores and NBI 10 minutes after each last daily NAC in both groups (p < 0.05). Symptom scores and NBI were similar for the 2 groups, except for nasal obstruction and rhinorrhea, which were more marked in subjects with asthma and rhinitis, respectively. Nasal lavage eosinophils were increased after 4 days of challenges in both groups, but there was no change in sputum eosinophils. No cumulative effect or any late response were observed in any of the groups over the challenge period. Conclusion Multiple NAC may be a useful tool to study the pathophysiology of allergic rhinitis or its relationships with asthma. Trial registration ClinicalTrials.gov NCT01286129 PMID:21507261

  20. Alterations of the lung methylome in allergic airway hyper-responsiveness.

    PubMed

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

    2014-04-01

    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

  1. Allergic inflammation--innately homeostatic.

    PubMed

    Cheng, Laurence E; Locksley, Richard M

    2015-03-01

    Allergic inflammation is associated closely with parasite infection but also asthma and other common allergic diseases. Despite the engagement of similar immunologic pathways, parasitized individuals often show no outward manifestations of allergic disease. In this perspective, we present the thesis that allergic inflammatory responses play a primary role in regulating circadian and environmental inputs involved with tissue homeostasis and metabolic needs. Parasites feed into these pathways and thus engage allergic inflammation to sustain aspects of the parasitic life cycle. In response to parasite infection, an adaptive and regulated immune response is layered on the host effector response, but in the setting of allergy, the effector response remains unregulated, thus leading to the cardinal features of disease. Further understanding of the homeostatic pressures driving allergic inflammation holds promise to further our understanding of human health and the treatment of these common afflictions. PMID:25414367

  2. Protective Effect of an Antibody against Specific Extracellular Domain of TLR2 on Agonists-Driven Inflammatory and Allergic Response

    PubMed Central

    Guo, Tianwu; Cai, Jun; Peng, Yanxia; Zhang, Lifang; Lan, Qiaofen; Chen, Yanwen; Liao, Huanjin; Xie, Tong; Wu, Ping; Pan, Qingjun

    2016-01-01

    Specific blocking strategies of TLR2-mediated inflammatory signaling and hypersensitivity reactions may offer novel therapeutic strategies to prevent a variety of diseases. In this study, we investigated the blocking effects of a new anti-TLR2 antibody anti-T20 against a 20 mer peptide T20 located in the extracellular specific domain of mouse TLR2. In addition, the effects of the anti-T20 in vitro, measuring the inhibition of the IL-6 and TNF-α production in response to PGN, LTA, and Pam3CSK4-stimulated RAW264.7 cells, were determined. In vivo, the effects of anti-T20 on a lethal anaphylaxis model using PGN-challenged OVA allergic mice, including the rectal temperature and mortality, and serum levels of TNF-α, IL-6, and LTC4 were assayed. The results showed that anti-T20 specifically bound to TLR2 and significantly inhibited PGN, LTA, and Pam3CSK4-driven TNF-α and IL-6 production by RAW264.7 cells. Also, anti-T20 protected OVA allergic mice from PGN-induced lethal anaphylaxis, and the serum levels of TNF-α, IL-6, and LTC4 of anti-T20 treated PGN-challenged OVA allergic mice were decreased as compared to isotype control of anti-T20 treated mice. In summary, this study produced a new antibody against the specific extracellular domain of TLR2 which has protective effect on TLR2 agonists-driven inflammatory and allergic response. PMID:27213155

  3. Common aeroallergens in patients with asthma and allergic rhinitis living in southwestern part of Iran: based on skin prick test reactivity.

    PubMed

    Farrokhi, Shokrollah; Gheybi, Mohammad Kazzem; Movahed, Ali; Tahmasebi, Rahim; Iranpour, Dariush; Fatemi, Atena; Etemadan, Razieh; Gooya, Mostafa; Zandi, Sahar; Ashourinejad, Hamid; Alavizadeh, Sara; Khoddami, Shaghayegh

    2015-04-01

    Aeroallergens continue to have a key role in the pathogenesis of asthma and allergic diseases and have recently received increased attention in medical research throughout the world. The prevalence of aeroallergens vary in different regions, depending on the type of climate. The aim of the present study was to determine prevalence of the sensitivity to aeroallergens among patients with asthma and allergic rhinitis (AR), based on skin prick test (SPT) reactivity in the province of Bushehr, Iran. In this cross-sectional study, 743 patients were enrolled. The participants had asthma and AR and reacted to at least one allergen with SPT. Skin prick test with standard extracts including house dust mites (HDMs), animal dander, molds and pollens were performed on patients according to the herbal geography of the area. The male to female ratio and mean age of the patients were 1.03 and 27.6± 15.4 year, respectively. Out of 567 patients with AR, the common aeroallergens were HDMs (88.5%), molds (82.9%), animal dander (79.5%), weeds (77.6%), trees (75.5%) and grass pollen (71.5%). Moreover, among 176 patients with asthma, the prevalence of aeroallergens were HDMs (90.5 %), molds (80.7%), animal dander (77.5%), weeds (73.3%), trees (73.3%) and grass pollen (67.9%). The sensitivity to animal dander, Chenopodium album and Russian thistle pollens were significantly associated with the severity of AR. Moreover, sensitivity to animal dander such as cat and feather of birds, cockroach, Bermuda grass and Chenopodium album pollens were significantly associated with the severity of asthma. The results of this study revealed that HDM was the most common sensitizing aeroallergen in patients with asthma and AR. Molds and animal dander as indoor allergens were also common aeroallergens. We suggest that the hot weather and ambient humidity in the region may be the main cause of the change in the pattern of SPT reactivity. PMID:25780879

  4. The skin sensitization potential of four alkylalkanolamines.

    PubMed

    Leung, H W; Blaszcak, D L

    1998-04-01

    The skin sensitization potential of 4 alkylalkanolamines (N-methylethanolamine, N,N-dimethylethanolamine, N-methyldiethanolamine and N,N-diethylethanolamine), was evaluated in a guinea pig maximation procedure by the method of Magnusson and Kligman. While all 4 alkylalkanolamines tested were irritating to the guinea pig skin, only N-methylethanolamine showed potential to induce allergic contact dermatitis. None of the remaining 3 alkylalkanolamines exhibited clear skin responses suggestive of sensitization. PMID:9554055

  5. Adoptive transfer of experimental allergic encephalomyelitis: recipient response to myelin basic protein-reactive lymphocytes.

    PubMed

    Bouwer, H G; Hinrichs, D J

    1994-10-01

    We have used adoptive transfer of myelin basic protein (MBP)-reactive lymphocytes in the Lewis rat model of experimental allergic encephalomyelitis (EAE) to identify stages of effector cell development and to investigate the nature of the subsequent recipient response to the transferred cells. Depending on the timing of cell collection, lymph node cells (LNC) obtained from MBP-CFA (MBP emulsified in complete Freund's adjuvant)-immunized donors may directly transfer clinical disease; however, independent of disease development, recipients of LNC develop early onset of clinical disease following immunization of the recipients with MBP-CFA, consistent with the presence of MBP-memory cells in the LNC transfer inoculum. Similarly obtained spleen cells do not directly transfer disease and do not contain MBP-memory cells (as defined by the early onset of clinical disease following MBP-CFA challenge). Spleen cells adoptively transfer clinical disease only following in vitro culture stimulation with antigen or selected mitogens. Recipients of the primary culture-derived encephalitogenic spleen cells also develop an accelerated onset of clinical disease following MBP-CFA challenge, indicative of the presence of MBP-memory cells, and are not vaccinated. Encephalitogenic T cell lines adoptively transfer clinical disease, and in most cases recipients are vaccinated to MBP-CFA-induced active disease, but remain susceptible to adoptively transferred disease. Co-transfer of encephalitogenic T cell line cells with MBP-reactive lymph node or encephalitogenic spleen cells does not alter the vaccination response. We have found that during the process of T cell line development, the vaccinating phenotype is acquired following the second antigen stimulation cycle. These studies also demonstrate that regulation induced by T cell vaccination blocks the development of effector cells from precursor cells and that such regulation is also equally effective in blocking disease development in

  6. Using magnetic resonance imaging to quantify the inflammatory response following allergen challenge in allergic rhinitis.

    PubMed

    Leaker, Brian R; Scadding, Glenis; Jones, C Richard; Barnes, Peter J

    2015-12-01

    Current rhinometric and flow assessments measure nasal patency and are often poorly correlated with rhinitis symptoms. To evaluate magnetic resonance imaging (MRI) as a new method to measure inflammatory changes in nasal and sinus mucosa following nasal allergen challenge. A pilot study (n = 6) determined the optimal technical settings for MRI to measure inflammatory change which were then adopted for the main study. This study was a single blind, placebo-controlled, three-way crossover trial in 14 subjects with seasonal allergic rhinitis. Effects of cetirizine, cetirizine and pseudoephedrine (Cet+PE), or placebo on total nasal symptom scores (TNSS), peak nasal inspiratory flow (PNIF), nasal nitric oxide (nNO), acoustic rhinometry, and MRI end points following nasal intranasal allergen challenge were measured. There were significant changes in all parameters after allergen challenge (P < 0.01), except for nNO. MRI end points were less variable and more consistent than PNIF and acoustic rhinometry in detecting changes after allergen challenge. Total nasal airspace volume was the most sensitive and reproducible MRI measurement, with a mean reduction from -5.37 cm(3) (95%CI -7.35, -3.38; P < 0.001), which was maximal 60 min after allergen challenge. A change of one in TNSS corresponded to a change in MRI volume of -0.57 cm(3). There was an improvement in all parameters (except nNO) in subjects taking Cet+PE compared with placebo, however this did not achieve significance probably because of the small study size (overall analysis P > 0.07; comparison of active versus placebo P > 0.09). MRI provides novel insights into the anatomical inflammatory changes post allergen challenge and provides a new method for assessment of nasal patency and objective measurement of inflammatory responses. PMID:26733348

  7. Cohabitation with a sick partner increases allergic lung inflammatory response in mice.

    PubMed

    Hamasato, Eduardo Kenji; de Lima, Ana Paula Nascimento; de Oliveira, Ana Paula Ligeiro; dos Santos Franco, Adriana Lino; de Lima, Wothan Tavares; Palermo-Neto, João

    2014-11-01

    results suggest that allergic lung inflammatory response exacerbation in CSP mice is a consequence of the psychological stress induced by forced cohabitation with the sick partner. Strong involvement of the sympathetic nervous system (SNS) through adrenaline and noradrenaline release and a shift of the Th1/Th2 cytokine profile toward a Th2 response were considered to be the mechanisms underlying the cell recruitment to the animal's airways. PMID:24929194

  8. Proliferative responses of the skin to external stimuli.

    PubMed Central

    Marks, F; Fürstenberger, G

    1993-01-01

    The skin, in particular the epidermis, offers unique opportunities to investigate the induction and control of cellular proliferation and tissue homeostasis both under in vivo and in vitro conditions. Moreover, it represents one of the most feasible model systems for experimental cancer research. As the primary border of the body, the skin has important protective and defensive functions. A general response to external injury consists of a thickening of the epithelial layer (epidermal hyperplasia) combined with an inflammatory reaction. This hyperplastic transformation of the skin is a critical condition of skin tumor development (i.e., conversion and promotion) and of the wound response. It is believed to be due to a transformation of keratinocytes into an activated state characterized by an increased rate of proliferation and the ability to release a series of growth factors and other cytokines that coordinate the defense reaction (e.g., hyperproliferation, recruitment of leukocytes, activation of the immune system) along auto- and paracrine feedback loops. The initial and probably later phases of this response depend critically on a local release of eicosanoids such as prostaglandins and lipoxygenase-generated factors. A unique reaction seen upon phorbol ester treatment of mouse skin is a strong induction of the enzyme 8-lipoxygenase, which might be involved in skin tumor development by catalyzing the generation of clastogenic metabolites thought to play a role in the conversion stage. Hyperplasia may be considered to be the result of an imbalance between the rates of cell gain and cell loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8013432

  9. Thymic stromal lymphopoietin: master switch for allergic inflammation

    PubMed Central

    Liu, Yong-Jun

    2006-01-01

    Thymic stromal lymphopoietin (TSLP) is an interleukin (IL) 7–like cytokine that triggers dendritic cell–mediated T helper (Th)2 inflammatory responses. TSLP is highly expressed by keratinocytes in skin lesions of patients with atopic dermatitis and is associated with dendritic cell activation in situ, suggesting that TSLP might be a master switch for allergic inflammation at the epithelial cell–dendritic cell interface. New reports now establish a direct link between TSLP expression and the pathogenesis of atopic dermatitis and asthma in vivo, and begin to reveal the molecular mechanisms underlying TSLP-induced allergic inflammation. PMID:16432252

  10. Increased Mast Cell Density and Airway Responses to Allergic and Non-Allergic Stimuli in a Sheep Model of Chronic Asthma

    PubMed Central

    Van der Velden, Joanne; Barker, Donna; Barcham, Garry; Koumoundouros, Emmanuel; Snibson, Kenneth

    2012-01-01

    Background Increased mast cell (MC) density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. However, the time sequence for these changes and how they impact small airway function in asthma is not fully understood. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen. Methodology/Principal Findings MC density was examined on lung tissue from four spatially separate lung segments of allergic sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24 weeks. Lung tissue was collected from each segment 7 days following the final challenge. The density of tryptase-positive and chymase-positive MCs (MCT and MCTC respectively) was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase. MCT and MCTC density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05). The MCTC/MCT ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05). MCT and MCTC density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05). MCT density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01). Conclusions MCT and MCTC density in the small airways correlates with better lung function in this sheep model of chronic asthma. Whether this finding indicates that under some conditions mast cells have protective activities in asthma, or that other explanations are to be considered requires further investigation. PMID:22606346

  11. Suppression of allergic and inflammatory responses by essential oils derived from herbal plants and citrus fruits.

    PubMed

    Mitoshi, Mai; Kuriyama, Isoko; Nakayama, Hiroto; Miyazato, Hironari; Sugimoto, Keiichiro; Kobayashi, Yuko; Jippo, Tomoko; Kuramochi, Kouji; Yoshida, Hiromi; Mizushina, Yoshiyuki

    2014-06-01

    The aim of the present study was to investigate the biological activity of 20 essential oils (EOs) derived from herbal plants and citrus fruits. The in vitro anti-allergic and anti-inflammatory activities of these oils were investigated, and the EO which was found to have the strongest activity of the 20 EOs examined, was investigated further to identify its components and bioactive compounds. The in vitro anti-allergic activity was determined by measuring the release of β-hexosaminidase from rat basophilic leukemia (RBL-2H3) cells treated with the calcium ionophore, A23187. The in vitro anti-inflammatory activity was determined by measuring the production of tumor necrosis factor-α (TNF-α) in RAW264.7 murine macrophages treated with lipopolysaccharide. Among the EOs examined, lemongrass [Cymbopogon citratus (DC.) Stapf] elicited the strongest anti-allergic and anti-inflammatory effects. A principal component of this EO is citral (3,7-dimethyl-2,6-octadien-1-al) (74.5%), a mixture of the stereoisomers, geranial (trans-citral, 40.16%) and neral (cis-citral, 34.24%), as determined by chromatography-mass spectrometry analysis. The activities of citral and geranial are similar to those of lemongrass EO. These compounds elicited significant in vivo anti-allergic and anti-inflammatory effects, suppressing an immunoglobulin E (IgE)-induced passive cutaneous anaphylactic reaction in mice and a 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory mouse ear edema, respectively. Our data demonstrate that lemongrass EO and its constituents, citral and geranial, may be a therapeutic candidate for allergic and inflammatory diseases. PMID:24682420

  12. Attenuated skin blood flow response to hyperthermia in paraplegic men.

    PubMed

    Freund, P R; Brengelmann, G L; Rowell, L B; Halar, E

    1984-04-01

    To clarify how skin and internal temperatures interact in control of skin blood flow, five male paraplegic subjects (lesions at the level of thoracic vertebrae 1-11) (29-47 yr old) were heated in water-perfused suits to elevate oral temperature (To) 1-1.5 degrees C. In part I only the insensate skin was heated; sensate skin was kept at 32-34 degrees C. No appreciable elevation of forearm blood flow (FBF) or sweating occurred, even with To at 38 degrees C. In part II the suit was applied to the whole body so that skin temperature was 40 degrees C, except for one arm that remained at 32-34 degrees C for FBF measurement. Sweating was noted above the lesion in all but one subject. FBF increased in all subjects but was far below levels previously reported for hyperthermic normal men; also, thresholds appeared elevated. To the extent that effector connections are intact, attenuated FBF response implies that either 1) some vasoconstrictor bias associated with cardiovascular regulation is active or 2) thermoregulatory effector outflow is diminished. If the latter is true, it follows that the effector outflow reduction relates to diminished afferent input. But the component of the effector outflow contributed by peripheral thermoreception is small; thus these findings may indicate that what is lacking in the afferent input is central thermoreception from below the lesion, possibly from the spinal cord itself. PMID:6725058

  13. Emerging concepts: mast cell involvement in allergic diseases.

    PubMed

    Modena, Brian D; Dazy, Kristen; White, Andrew A

    2016-08-01

    In a process known as overt degranulation, mast cells can release all at once a diverse array of products that are preformed and present within cytoplasmic granules. This occurs typically within seconds of stimulation by environmental factors and allergens. These potent, preformed mediators (ie, histamine, heparin, serotonin, and serine proteases) are responsible for the acute symptoms experienced in allergic conditions such as allergic conjunctivitis, allergic rhinitis, allergy-induced asthma, urticaria, and anaphylaxis. Yet, there is reason to believe that the actions of mast cells are important when they are not degranulating. Mast cells release preformed mediators and inflammatory cytokines for periods after degranulation and even without degranulating at all. Mast cells are consistently seen at sites of chronic inflammation, including nonallergic inflammation, where they have the ability to temper inflammatory processes and shape tissue morphology. Mast cells can trigger actions and chemotaxis in other important immune cells (eg, eosinophils and the newly discovered type 2 innate lymphocytes) that then make their own contributions to inflammation and disease. In this review, we will discuss the many known and theorized contributions of mast cells to allergic diseases, focusing on several prototypical allergic respiratory and skin conditions: asthma, chronic rhinosinusitis, aspirin-exacerbated respiratory disease, allergic conjunctivitis, atopic dermatitis, and some of the more common medication hypersensitivity reactions. We discuss traditionally accepted roles that mast cells play in the pathogenesis of each of these conditions, but we also delve into new areas of discovery and research that challenge traditionally accepted paradigms. PMID:26976119

  14. Inspiration-induced vascular responses in finger dorsum skin.

    PubMed

    Mayrovitz, Harvey N; Groseclose, Edye E

    2002-03-01

    A rapid and deep inspiration triggers a sympathetically mediated transient vasoconstriction of skin arterioles (inspiratory gasp vascular response, IGVR). Because the IGVR has been most often measured and studied in skin that is rich in arteriovenous anastomoses (AVAs), such as the palmar aspect of the distal phalanx or plantar aspect of the toes, there is little information on its features in skin areas not dominated by thermoregulatory AVAs. Thus, the dependence of the magnitude of the IGVR on AVAs is unclear. We reasoned that if responses in a region of low AVA density, such as the finger dorsum distal phalanx, were comparable to those in AVA-rich skin, this would clarify the issue. Further, it might then be possible to use such areas to provide a useful complementary target for future study of sympathetically induced vasoconstriction. To test this, we determined the features of the finger dorsum IGVR in 28 healthy volunteers (age 19-57 years, 14 males) in whom distal phalanx skin blood perfusion (SBF) was monitored by laser-Doppler during 21 sequential IGVRs, each separated by 2 min. IGVR was quantified as the minimum SBF during each IGVR, expressed as a percentage of each immediately preceding 2-min SBF average. Results (mean +/- SD) revealed an overall IGVR of 72.2 +/- 16.7%, which is very near that reported from studies on the AVA-rich palmar finger pad. We therefore conclude that the IGVR does not depend on the presence of AVAs and that the dorsal distal phalanx is a viable alternative for the study of sympathetically related neurovascular responses. PMID:11866546

  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. Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

    PubMed Central

    Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

    2015-01-01

    Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

  17. 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

  18. Effects of Swimming on the Inflammatory and Redox Response in a Model of Allergic Asthma.

    PubMed

    Brüggemann, T R; Ávila, L C M; Fortkamp, B; Greiffo, F R; Bobinski, F; Mazzardo-Martins, L; Martins, D F; Duarte, M M M F; Dafre, A; Santos, A R S; Silva, M D; Souza, L F; Vieira, R P; Hizume-Kunzler, D C

    2015-06-01

    In this study we hypothesized that swimming during sensitization phase could result in a preventive effect in mice with allergic asthma. Swiss mice were divided into 4 groups: Control and Swimming (non-sensitized), OVA and OVA+Swimming (sensitized). The allergic inflammation was induced by 2 intraperitoneal injections and 4 aerosol challenges using ovalbumin. Swimming sessions were performed at high intensity over 3 weeks. 48 h after the last challenge mice were euthanized. Swimming decreased OVA-increased total IgE, IL-1, IL-4, IL-5 and IL-6 levels, as well as the number of total cells, lymphocytes and eosinophils in bronchoalveolar lavage fluid, (p<0.05). Simultaneously, swimming also increased IL-10 and glutathione levels in the Swimming and OVA+Swimming groups (p<0.05). The levels of glutathione peroxidase and catalase were increased only in the Swimming group when compared to all groups (p<0.05). 21 days of swimming resulted in an attenuation of pulmonary allergic inflammation followed by an increase of glutathione levels in the OVA group. Swimming only increased the levels of glutathione peroxidase and catalase in non-sensitized mice (p<0.05). These data suggest that the pulmonary anti-inflammatory effects produced by 3 weeks of high-intensity swimming in this model of OVA-induced asthma may be, at least partly, modulated by reduced oxidative stress and increased IL-10 production. PMID:25837246

  19. Key Role of CRF in the Skin Stress Response System

    PubMed Central

    Zmijewski, Michal A.; Zbytek, Blazej; Tobin, Desmond J.; Theoharides, Theoharis C.; Rivier, Jean

    2013-01-01

    The discovery of corticotropin-releasing factor (CRF) or CRH defining the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis, along with the identification of the corresponding receptors (CRFRs 1 and 2), represents a milestone in our understanding of central mechanisms regulating body and local homeostasis. We focused on the CRF-led signaling systems in the skin and offer a model for regulation of peripheral homeostasis based on the interaction of CRF and the structurally related urocortins with corresponding receptors and the resulting direct or indirect phenotypic effects that include regulation of epidermal barrier function, skin immune, pigmentary, adnexal, and dermal functions necessary to maintain local and systemic homeostasis. The regulatory modes of action include the classical CRF-led cutaneous equivalent of the central HPA axis, the expression and function of CRF and related peptides, and the stimulation of pro-opiomelanocortin peptides or cytokines. The key regulatory role is assigned to the CRFR-1α receptor, with other isoforms having modulatory effects. CRF can be released from sensory nerves and immune cells in response to emotional and environmental stressors. The expression sequence of peptides includes urocortin/CRF→pro-opiomelanocortin→ACTH, MSH, and β-endorphin. Expression of these peptides and of CRFR-1α is environmentally regulated, and their dysfunction can lead to skin and systemic diseases. Environmentally stressed skin can activate both the central and local HPA axis through either sensory nerves or humoral factors to turn on homeostatic responses counteracting cutaneous and systemic environmental damage. CRF and CRFR-1 may constitute novel targets through the use of specific agonists or antagonists, especially for therapy of skin diseases that worsen with stress, such as atopic dermatitis and psoriasis. PMID:23939821

  20. Key role of CRF in the skin stress response system.

    PubMed

    Slominski, Andrzej T; Zmijewski, Michal A; Zbytek, Blazej; Tobin, Desmond J; Theoharides, Theoharis C; Rivier, Jean

    2013-12-01

    The discovery of corticotropin-releasing factor (CRF) or CRH defining the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis, along with the identification of the corresponding receptors (CRFRs 1 and 2), represents a milestone in our understanding of central mechanisms regulating body and local homeostasis. We focused on the CRF-led signaling systems in the skin and offer a model for regulation of peripheral homeostasis based on the interaction of CRF and the structurally related urocortins with corresponding receptors and the resulting direct or indirect phenotypic effects that include regulation of epidermal barrier function, skin immune, pigmentary, adnexal, and dermal functions necessary to maintain local and systemic homeostasis. The regulatory modes of action include the classical CRF-led cutaneous equivalent of the central HPA axis, the expression and function of CRF and related peptides, and the stimulation of pro-opiomelanocortin peptides or cytokines. The key regulatory role is assigned to the CRFR-1α receptor, with other isoforms having modulatory effects. CRF can be released from sensory nerves and immune cells in response to emotional and environmental stressors. The expression sequence of peptides includes urocortin/CRF→pro-opiomelanocortin→ACTH, MSH, and β-endorphin. Expression of these peptides and of CRFR-1α is environmentally regulated, and their dysfunction can lead to skin and systemic diseases. Environmentally stressed skin can activate both the central and local HPA axis through either sensory nerves or humoral factors to turn on homeostatic responses counteracting cutaneous and systemic environmental damage. CRF and CRFR-1 may constitute novel targets through the use of specific agonists or antagonists, especially for therapy of skin diseases that worsen with stress, such as atopic dermatitis and psoriasis. PMID:23939821

  1. RELATIVE POTENCY OF MOLD AND HOUSE DUST MITE EXTRACTS IN INDUCING ALLERGIC RESPONSES IN BALB/C MICE

    EPA Science Inventory

    Rationale: Mold has been associated with the exacerbation of allergic asthma. However, its role in induction of allergic asthma is not clear. Using a previously developed mouse model for allergic asthma, we compared potencies of two fungal extracts (Metarhizium anisop...

  2. A randomized controlled study of peanut oral immunotherapy (OIT): clinical desensitization and modulation of the allergic response

    PubMed Central

    Varshney, Pooja; Jones, Stacie M.; Scurlock, Amy M.; Perry, Tamara T.; Kemper, Alex; Steele, Pamela; Hiegel, Anne; Kamilaris, Janet; Carlisle, Suzanne; Yue, Xiaohong; Kulis, Mike; Pons, Laurent; Vickery, Brian; Burks, A. Wesley

    2011-01-01

    Background Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials. Objective To investigate the safety and effectiveness of OIT for peanut allergy in a double blind, placebo-controlled study. Methods In this multicenter study, peanut-allergic children ages 1-16 years received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge at approximately one year. Titrated skin prick tests (SPT) and laboratory studies were performed at regular intervals. Results Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study due to allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (N=16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), while placebo subjects (N=9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg) [p<0.001]. In contrast to the placebo group, the peanut OIT group showed reductions in SPT size (p<0.001), IL-5 (p=0.01), and IL-13 (p=0.02) and increases in peanut-specific IgG4 (p<0.001). Peanut OIT subjects had initial increases in peanut-specific IgE (p<0.01) but did not show significant change from baseline by the time of OFC. The ratio of FoxP3 hi: FoxP3 intermediate CD4+CD25+ T cells increased at the time of OFC (p=0.04) in peanut OIT subjects. Conclusion These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The present study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance. PMID:21377034

  3. Cutting Edge: Drebrin-Regulated Actin Dynamics Regulate IgE-Dependent Mast Cell Activation and Allergic Responses.

    PubMed

    Law, Mankit; Lee, YongChan; Morales, J Luis; Ning, Gang; Huang, Weishan; Pabon, Jonathan; Kannan, Arun K; Jeong, Ah-Reum; Wood, Amie; Carter, Chavez; Mohinta, Sonia; Song, Jihong; August, Avery

    2015-07-15

    Mast cells play critical roles in allergic responses. Calcium signaling controls the function of these cells, and a role for actin in regulating calcium influx into cells has been suggested. We have previously identified the actin reorganizing protein Drebrin as a target of the immunosuppressant 3,5-bistrifluoromethyl pyrazole, which inhibits calcium influx into cells. In this study, we show that Drebrin(-/-) mice exhibit reduced IgE-mediated histamine release and passive systemic anaphylaxis, and Drebrin(-/-) mast cells also exhibit defects in FcεRI-mediated degranulation. Drebrin(-/-) mast cells exhibit defects in actin cytoskeleton organization and calcium responses downstream of the FcεRI, and agents that relieve actin reorganization rescue mast cell FcεRI-induced degranulation. Our results indicate that Drebrin regulates the actin cytoskeleton and calcium responses in mast cells, thus regulating mast cell function in vivo. PMID:26056254

  4. 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

  5. Allergic inflammatory response to short ragweed allergenic extract in HLA-DQ transgenic mice lacking CD4 gene.

    PubMed

    Chapoval, Svetlana P; Iijima, Koji; Marietta, Eric V; Smart, Michele K; Chapoval, Andrei I; Andrews, Amy G; David, Chella S

    2002-01-15

    To investigate the role of HLA-DQ molecules and/or CD4(+) T cells in the pathogenesis of allergic asthma, we generated HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous class II (Abeta(null)) and CD4 genes and challenged them intranasally with short ragweed allergenic extract (SRW). We found that DQ6/CD4(null) mice developed a strong eosinophilic infiltration into the bronchoalveolar lavage and lung tissue, while DQ8/CD4(null) mice were normal. However, neither cytokines nor eosinophil peroxidase in the bronchoalveolar lavage of DQ6/CD4(null) mice was found. In addition, the airway reactivity to methacholine was elevated moderately in DQ6/CD4(null) mice compared with the high response in DQ/CD4(+) counterparts and was only partially augmented by CD4(+) T cell transfer. The DQ6/CD4(null) mice showed Th1/Th2-type cytokines and SRW-specific Abs in the immune sera in contrast to a direct Th2 response observed in DQ6/CD4(+) mice. The proliferative response of spleen mononuclear cells and peribronchial lymph node cells demonstrated that the response to SRW in DQ6/CD4(null) mice was mediated by HLA-DQ-restricted CD4(-)CD8(-)NK1.1(-) T cells. FACS analysis of PBMC and spleen mononuclear cells demonstrated an expansion of double-negative (DN) CD4(-)CD8(-)TCRalphabeta(+) T cells in SRW-treated DQ6/CD4(null) mice. These cells produced IL-4, IL-5, IL-13, and IFN-gamma when stimulated with immobilized anti-CD3. IL-5 ELISPOT assay revealed that DN T cells were the cellular origin of IL-5 in allergen-challenged DQ6/CD4(null) mice. Our study shows a role for HLA-DQ-restricted CD4(+) and DN T cells in the allergic response. PMID:11777987

  6. Pulmonary Allergic Responses Augment IL-13 Secretion by Circulating Basophils yet Suppress IFN-alpha from Plasmacytoid DCs

    PubMed Central

    Schroeder, John T.; Bieneman, Anja P.; Chichester, Kristin L.; Breslin, Linda; Xiao, HuiQing; Liu, Mark C.

    2011-01-01

    Background Allergic inflammatory processes may have the capacity to propagate systemically through the actions of circulating leukocytes. Consequently, basophils from allergic individuals are often “primed”, as evidenced by their hyper-responsiveness in vitro. IFN-α, secreted predominately by plasmacytoid DCs, suppresses basophil priming for IL-13 production in vitro. Objective This study sought in vivo correlates, arising during experimental allergen challenge, that support an “axis-interplay” between basophils and pDCs. Methods Using segmental allergen challenge in the lung, the immune responses of both cell types from blood were investigated in volunteers (n=10) before and 24h after allergen exposure. These responses were then correlated with inflammatory parameters measured in bronchoalveolar lavage fluids. Results In blood, segmental allergen challenge significantly augmented IL-13 secretion by basophils induced by IL-3 (p=0.009) yet reduced IFN-α secreted by plasmacytoid dendritic cells stimulated with CpG (p=0.018). Both parameters were negatively correlated (p=0.0015), at least among those subjects secreting the latter. Circulating basophil IL-13 responses further correlated with post-segmental allergen challenge bronchoalveolar lavage parameters including IL-13 protein (p=0.04), basophil (p=0.051), eosinophil (p=0.0018) and total cell counts (p<0.003). Basophil and IL-13 levels in bronchoalveolar lavage likewise correlated (p=0.0002). Conclusions These results support a mechanism of immune regulation whereby allergen reduces innate immune responses and IFN-α production by plasmacytoid dendritic cells, resulting in enhanced inflammation and basophil cytokine production at sites of allergen exposure. PMID:20184608

  7. 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 ...

  8. Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis

    PubMed Central

    Wei-xu, Hu; Wen-yun, Zhou; Xi-ling, Zhu; Zhu, Wen; Li-hua, Wu; Xiao-mu, Wu; Hui-ping, Wei; Wen-ding, Wang; Dan, He; Qin, Xiang

    2016-01-01

    This study aims to determine whether the combined blockade of IL-1β and TNF-α can alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-α IgY treatment group; (4) the 0.1% anti-IL-1β IgY treatment group; (5) the 0.1% combined anti-IL-1β and TNF-α IgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright's staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P < 0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P < 0.05) in the combined 0.1% anti-IL-1β- and TNF-α IgY-treated guinea pigs. The data suggest that topical blockade of IL-1β and TNF-α could reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs. PMID:27046957

  9. Pycnogenol inhibits immunoglobulin E-mediated allergic response in mast cells.

    PubMed

    Choi, Yun Ho; Yan, Guang Hai

    2009-12-01

    IgE-dependent mast cell activation is known to be associated with the allergic diseases. Pycnogenol (PYC) is a standardized extract of the bark of French maritime pine containing bioflavonoids with a potent antioxidant activity. The antiallergic activity of PYC was evaluated using both in vivo and in vitro experimental models. Oral administration of PYC significantly inhibited anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis in rats. In an in vitro study, PYC dose-dependently reduced histamine release from rat peritoneal mast cells (RPMC) triggered by anti-DNP IgE. PYC inhibited the protein expression and secretion of tumor necrosis factor-alpha and interleukin-6 in anti-DNP IgE-stimulated RPMC. Moreover, PYC decreased anti-DNP IgE-induced calcium uptake into RPMC. Furthermore, PYC suppressed nuclear factor-kappa B activation. From these results, the clinical use of PYC in the mast cell-mediated immediate-type allergic diseases is proposed. PMID:19441014

  10. Effect of Dangguibohyul-Tang, a Mixed Extract of Astragalus membranaceus and Angelica sinensis, on Allergic and Inflammatory Skin Reaction Compared with Single Extracts of Astragalus membranaceus or Angelica sinensis

    PubMed Central

    Choi, You Yeon; Kim, Mi Hye; Hong, Jongki

    2016-01-01

    Dangguibohyul-tang (DBT), herbal formula composed of Astragalus membranaceus (AM) and Angelica sinensis (AS) at a ratio of 5 : 1, has been used for the treatment of various skin diseases in traditional medicine. We investigated the effect of DBT on allergic and inflammatory skin reaction in atopic dermatitis-like model compared to the single extract of AM or AS. DBT treatment showed the remission of clinical symptoms, including decreased skin thickness and scratching behavior, the total serum IgE level, and the number of mast cells compared to DNCB group as well as the single extract of AM- or AS-treated group. Levels of cytokines (IL-4, IL-6, IFN-γ, TNF-α, and IL-1β) and inflammatory mediators (NF-κB, phospho-IκBα, and phospho-MAPKs) were significantly decreased in AM, AS, and DBT groups. These results demonstrated that AM, AS, and DBT may have the therapeutic property on atopic dermatitis by inhibition of allergic and inflammatory mediators and DBT formula; a mixed extract of AM and AS based on the herb pairs theory especially might be more effective on antiallergic reaction as compared with the single extract of AM or AS. PMID:27051450

  11. Allergic bronchopulmonary aspergillosis (ABPA): studies on the general and specific humoral response.

    PubMed

    Sandhu, R S; Bardana, E J; Khan, Z U; Dordevich, D M

    1978-04-14

    Serum specimens from 138 patients suffering from chronic respiratory disorders including 63 with allergic bronchopulmonary aspergillosis (ABPA), 2o with suspected ABPA, 15 with pulmonary tuberculosis, 14 with bronchial asthma, 10 with chronic bronchitis and 6 with miscellaneous pulmonary conditions were studied for circulating antibodies to Aspergillus. The ammonium sulfate test was empolyed with an iodine-125 labeled mycelial component derived from Aspergillus fumigatus. When compared to normal controls from the same area, this test indicated that sera from 82 per cent of patients with ABPA had elevated binding titers to the radiolabeled antigenic component. Immunodiffusion using a culture filtrate antigen from A. fumigatus, revealed precipitating antibody to this fungus in 89 percent of sera from ABP patients. The majority of patients with ABPA demonstrated marked elevations of total serum IgE, moderate elevations of serum IgA and IgD and slightly increased levels of IgG and IgM. PMID:652026

  12. Allergic inhalant dermatitis attributable to marijuana exposure in a dog.

    PubMed

    Evans, A G

    1989-12-01

    Exposure to marijuana was believed to be responsible for clinical signs consistent with allergic inhalant dermatitis in a dog. The dog had facial and pedal pruritus associated with bilateral ocular discharge. Clinical signs resolved when the dog was kenneled, but returned when the dog was returned to its home. The results of intradermal skin testing, using a standard tray of 51 inhalant extracts, did not adequately account for the dog's clinical signs. Later, the owners indicated that previous residents of the owners' home had cultivated marijuana intensively inside and outside of the home. Intradermal skin testing with a source of marijuana pollen extract was performed, yielding a positive reaction in the dog and a negative reaction in another dog without clinical or historical evidence of allergic inhalant dermatitis. The affected dog was treated successfully and exclusively by hyposensitization with marijuana pollen extract. PMID:2599943

  13. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma.

    PubMed

    Lee, Yong Gyu; Jeong, Jong Jin; Nyenhuis, Sharmilee; Berdyshev, Evgeny; Chung, Sangwoon; Ranjan, Ravi; Karpurapu, Manjula; Deng, Jing; Qian, Feng; Kelly, Elizabeth A B; Jarjour, Nizar N; Ackerman, Steven J; Natarajan, Viswanathan; Christman, John W; Park, Gye Young

    2015-06-01

    Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. PMID:25360868

  14. Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response.

    PubMed

    Charbonnier, Anne-Sophie; Hammad, Hamida; Gosset, Philippe; Stewart, Geoffrey A; Alkan, Sefik; Tonnel, André-Bernard; Pestel, Joël

    2003-01-01

    Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4(+) T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-gamma(high)/IL-4(low)] and Der p 1-pulsed P-DC, a Th2 profile (IFN-gamma(low)/IL-4(high)). In healthy donors, no T cell polarization (IFN-gamma(low)/IL-4(low)) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors. PMID:12525566

  15. Interleukin-1 Receptor and Caspase-1 Are Required for the Th17 Response in Nitrogen Dioxide–Promoted Allergic Airway Disease

    PubMed Central

    Martin, Rebecca A.; Ather, Jennifer L.; Lundblad, Lennart K. A.; Suratt, Benjamin T.; Boyson, Jonathan E.; Budd, Ralph C.; Alcorn, John F.; Flavell, Richard A.; Eisenbarth, Stephanie C.

    2013-01-01

    Nitrogen dioxide (NO2) is an environmental pollutant and endogenously generated oxidant associated with the development, severity, and exacerbation of asthma. NO2 exposure is capable of allergically sensitizing mice to the innocuous inhaled antigen ovalbumin (OVA), promoting neutrophil and eosinophil recruitment, and a mixed Th2/Th17 response upon antigen challenge that is reminiscent of severe asthma. However, the identity of IL-17A–producing cells and the mechanisms governing their ontogeny in NO2-promoted allergic airway disease remain unstudied. We measured the kinetics of lung inflammation after antigen challenge in NO2-promoted allergic airway disease, including inflammatory cells in bronchoalveolar lavage and antigen-specific IL-17A production from the lung. We determined that IL-17A+ cells were predominately CD4+T cell receptor (TCR)β+ Th17 cells, and that a functional IL-1 receptor was required for Th17, but not Th2, cytokine production after in vitro antigen restimulation of lung cells. The absence of natural killer T cells, γδ T cells, or the inflammasome scaffold nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain (Nlrp)3 did not affect the development of NO2-promoted allergic inflammation or IL-17A production. Similarly, neutrophil depletion or the neutralization of IL-1α during sensitization exerted no effect on these parameters. However, the absence of caspase-1 significantly reduced IL-17A production from lung cells without affecting Th2 cytokines or lung inflammation. Finally, the intranasal administration of IL-1β and the inhalation of antigen promoted allergic sensitization that was reflected by neutrophilic airway inflammation and IL-17A production from CD4+TCRβ+ Th17 cells subsequent to antigen challenge. These data implicate a role for caspase-1 and IL-1β in the IL-1 receptor–dependent Th17 response manifest in NO2-promoted allergic airway disease. PMID:23371061

  16. 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

  17. Allergic Responses Induced by a Fungal Biopesticide Metarhizium anisopliae and House Dust Mite Are Compared in a Mouse Model.

    PubMed

    Ward, Marsha D W; Chung, Yong Joo; Copeland, Lisa B; Doerfler, Donald L

    2011-01-01

    Biopesticides can be effective in controlling their target pest. However, research regarding allergenicity and asthma development is limited. We compared the ability of fungal biopesticide Metarhizium anisopliae (MACA) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration at doubling doses (2.5-80 μg protein) 4X over a four-week period. Three days after the last exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The extracts' relative allergenicity was evaluated based on response robustness (lowest significant dose response compared to control (0 μg)). MACA induced a more robust serum total IgE response than HDM. However, in the antigen-specific IgE assay, a similar dose of both MACA and HDM was required to achieve the same response level. Our data suggest a threshold dose of MACA for allergy induction and that M. anisopliae may be similar to HDM in allergy induction potential. PMID:21785589

  18. Allergic Responses Induced by a Fungal Biopesticide Metarhizium anisopliae and House Dust Mite Are Compared in a Mouse Model

    PubMed Central

    Ward, Marsha D. W.; Chung, Yong Joo; Copeland, Lisa B.; Doerfler, Donald L.

    2011-01-01

    Biopesticides can be effective in controlling their target pest. However, research regarding allergenicity and asthma development is limited. We compared the ability of fungal biopesticide Metarhizium anisopliae (MACA) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration at doubling doses (2.5–80 μg protein) 4X over a four-week period. Three days after the last exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The extracts' relative allergenicity was evaluated based on response robustness (lowest significant dose response compared to control (0 μg)). MACA induced a more robust serum total IgE response than HDM. However, in the antigen-specific IgE assay, a similar dose of both MACA and HDM was required to achieve the same response level. Our data suggest a threshold dose of MACA for allergy induction and that M. anisopliae may be similar to HDM in allergy induction potential. PMID:21785589

  19. The Endogenous Th17 Response in NO2-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

    PubMed Central

    Martin, Rebecca A.; Ather, Jennifer L.; Daggett, Rebecca; Hoyt, Laura; Alcorn, John F.; Suratt, Benjamin T.; Weiss, Daniel J.; Lundblad, Lennart K. A.; Poynter, Matthew E.

    2013-01-01

    Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. PMID:24069338

  20. RELATIVE POTENCY OF FUNGAL EXTRACTS IN INDUCING ALLERGIC ASTHMA-LIKE RESPONSES IN BALB/C MICE

    EPA Science Inventory

    Indoor mold has been associated with the development of allergic asthma. However, relative potency of molds in the induction of allergic asthma is not clear. In this study, we tested the relative potency of fungal extracts (Metarizium anisophilae [MACA], Stachybotrys ...

  1. Improved electrode paste provides reliable measurement of galvanic skin response

    NASA Technical Reports Server (NTRS)

    Day, J. L.

    1966-01-01

    High-conductivity electrode paste is used in obtaining accurate skin resistance or skin potential measurements. The paste is isotonic to perspiration, is nonirritating and nonsensitizing, and has an extended shelf life.

  2. A Controlled Challenge Study on Di(2-ethylhexyl) Phthalate (DEHP) in House Dust and the Immune Response in Human Nasal Mucosa of Allergic Subjects

    PubMed Central

    Deutschle, Tom; Reiter, Rudolf; Butte, Werner; Heinzow, Birger; Keck, Tilman; Riechelmann, Herbert

    2008-01-01

    Background Few studies have yet addressed the effects of di(2-ethylhexyl) phthalate (DEHP) in house dust on human nasal mucosa. Objectives We investigated the effects of house dust containing DEHP on nasal mucosa of healthy and house dust mite (HDM)–allergic subjects in a short-term exposure setting. Methods We challenged 16 healthy and 16 HDM-allergic subjects for 3 hr with house dust at a concentration of 300 μg/m3 containing either low (0.41 mg/g) or high (2.09 mg/g) levels of DEHP. Exposure to filtered air served as control. After exposure, we measured proteins and performed a DNA microarray analysis. Results Nasal exposure to house dust with low or high DEHP had no effect on symptom scores. Healthy subjects had almost no response to inhaled dust, but HDM-allergic subjects showed varied responses: DEHPlow house dust increased eosinophil cationic protein, granulocyte-colony–stimulating factor (G-CSF), interleukin (IL)-5, and IL-6, whereas DEHPhigh house dust decreased G-CSF and IL-6. Furthermore, in healthy subjects, DEHP concentration resulted in 10 differentially expressed genes, whereas 16 genes were differentially expressed in HDM-allergic subjects, among them anti-Müllerian hormone, which was significantly up-regulated after exposure to DEHPhigh house dust compared with exposure to DEHPlow house dust, and fibroblast growth factor 9, IL-6, and transforming growth factor-β1, which were down-regulated. Conclusions Short-term exposure to house dust with high concentrations of DEHP has attenuating effects on human nasal immune response in HDM-allergic subjects, concerning both gene expression and cytokines. PMID:19057701

  3. Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses

    PubMed Central

    Ohmichi, Yukari; Hirakawa, Jotaro; Imai, Yasuyuki; Fukuda, Minoru

    2011-01-01

    Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4+CD25+ regulatory T cells (Treg cells). Compared with the homing of CD4+CD25− conventional T cells, the homing of CD4+CD25+ Treg cells to NALT was less dependent on the L-selectin–PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses. PMID:21518796

  4. An evaluation of short-term corticosteroid response in perennial allergic rhinitis using histamine and adenosine monophosphate nasal challenge

    PubMed Central

    Wilson, Andrew M; Sims, Erika J; Orr, Linda C; Robb, Fiona; Lipworth, Brian J

    2003-01-01

    Aims To evaluate the role of AMP nasal challenge as a measure of short-term treatment response in patients receiving intranasal corticosteroids. Adenosine monophosphate (AMP) challenge has been shown to be a good inflammatory surrogate in the lower airways, but it has not been properly evaluated as a nasal challenge test. Methods Fourteen patients with perennial allergic rhinitis (PAR) were randomized to receive 2 weeks treatment with placebo (PL) or 200 µg intranasal mometasone furoate (MF) once daily in a randomized single-blind crossover study. AMP (25–800 mg ml−1) and histamine (0.25–8 mg ml−1) nasal challenge testing were performed after each treatment period with 30% decrease in minimal cross-sectional area (MCA). Domiciliary symptom data were collected. Results There was a significant (P < 0.05) improvement in PC30 MCA and nasal volume with AMP but not with histamine comparing MF vs PL. This amounted to a 2.8 (95% CI 1.5, 4.0) and 0.7 (95% CI −0.5, 1.9) doubling-dose change for AMP and histamine challenges, respectively. There were significant (P < 0.05) improvements in nasal symptoms and quality of life. Conclusions AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR. PMID:12680883

  5. 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

  6. Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis.

    PubMed

    Agarwal, Ritesh; Aggarwal, Ashutosh N; Sehgal, Inderpaul S; Dhooria, Sahajal; Behera, Digambar; Chakrabarti, Arunaloke

    2016-01-01

    The role of total and specific IgE in monitoring treatment responses in allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. Here in, we evaluate the utility of total and Aspergillus fumigatus specific IgE in the follow-up of ABPA. Eighty-one consecutive treatment-naïve patients of ABPA (acute stage) with pulmonary infiltrates and bronchiectasis underwent measurement of total and A. fumigatus specific IgE at baseline, after 8 weeks of glucocorticoid therapy, and during exacerbations. There was clinical and radiological improvement after treatment with median decline of total IgE by 51.9%. The total IgE declined by at least 35%, 25% and 20% in 69 (85.2%), 76 (93.6%) and 78 (96.3%) patients, respectively. On the other hand, the A. fumigatus specific IgE increased in 42 (51.9%) subjects, and the mean increase was 1.4%, after 8 weeks. Among 13 patients with exacerbation, 12 (92.3%) had a rise of total IgE by >50%. The A. fumigatus specific IgE increased in only five (38.5%) subjects during exacerbation. Thus, the total IgE is a useful test in monitoring treatment responses in ABPA while A. fumigatus specific IgE has limited utility. PMID:26575791

  7. Exposure to Aedes aegypti Bites Induces a Mixed-Type Allergic Response following Salivary Antigens Challenge in Mice

    PubMed Central

    Barros, Michele S.; Gomes, Eliane; Gueroni, Daniele I.; Ramos, Anderson D.; Mirotti, Luciana; Florsheim, Esther; Bizzarro, Bruna; Lino, Ciro N. R.; Maciel, Ceres; Lino-Dos-Santos-Franco, Adriana; Tavares-de-Lima, Wothan; Capurro, Margareth L.; Russo, Momtchilo

    2016-01-01

    Classical studies have shown that Aedes aegypti salivary secretion is responsible for the sensitization to mosquito bites and many of the components present in saliva are immunogenic and capable of inducing an intense immune response. Therefore, we have characterized a murine model of adjuvant-free systemic allergy induced by natural exposure to mosquito bites. BALB/c mice were sensitized by exposure to A. aegypti mosquito bites and intranasally challenged with phosphate-buffered saline only or the mosquito’s salivary gland extract (SGE). Blood, bronchoalveolar lavage (BAL) and lung were collected and evaluated for cellularity, histopathological analyses, cytokines and antibody determination. Respiratory pattern was analyzed by Penh measurements and tracheal segments were obtained to study in vitro reactivity to methacholine. BAL recovered from sensitized mice following challenge with SGE showed an increased number of eosinophils and Th2 cytokines such as IL-4, IL-5 and IL-13. Peribronchoalveolar eosinophil infiltration, mucus and collagen were also observed in lung parenchyma of sensitized mice, suggesting the development of a typical Th2 response. However, the antibody profile in serum of these mice evidenced a mixed-type response with presence of both, IgG1/IgE (Th2-related) and IgG2a (Th1-related) isotypes. In addition, changes in breathing pattern and tracheal reactivity to methacholine were not found. Taken together, our results show that A. aegypti bites trigger an atypical allergic reaction, with some classical cellular and soluble Th2 components in the lung, but also systemic Th1 and Th2 antibody isotypes and no change in either the respiratory pattern or the trachea responsiveness to agonist. PMID:27203689

  8. Additional support for the existence of skin conductance responses at unconditioned stimulus omission.

    PubMed

    Spoormaker, Victor I; Blechert, Jens; Goya-Maldonado, Roberto; Sämann, Philipp G; Wilhelm, Frank H; Czisch, Michael

    2012-11-15

    The existence of a skin conductance response to an expected but omitted aversive stimulus has recently been challenged. To counter this claim, we provide a review of the literature and a temporal analysis of two independent skin conductance data sets during aversive conditioning and extinction that demonstrates a consistent and reproducible skin conductance response at omission of an anticipated aversive stimulus. The validity of this so-called unconditioned stimulus (US) omission response is relevant for skin conductance modeling in the context of neuroimaging and more generally for conditioning theory. PMID:22922467

  9. Impaired sympathetic skin response in chronic obstructive pulmonary disease.

    PubMed

    Bir, Levent Sinan; Ozkurt, Sibel; Daloğlu, Güner; Kurt, Tülay

    2005-12-01

    The sympathetic skin response (SSR) is considered as one of the indexes of autonomic nervous system functions, especially related with the sudomotor function of unmyelinated sympathetic fibers. SSRs are recorded as the potentials with biphasic or multiphasic waveforms by conventional electromyography. SSRs are evaluated by measuring latency (time from the stimulus to the onset), amplitude, and area (the space under the curve of the waveform). Although dysautonomia is a feature of chronic obstructive pulmonary disease (COPD), as demonstrated by acetylcholine sweat-spot test, there are no data concerning SSR in COPD patients. In this study, we electrophysiologically investigated the sudomotor function of the sympathetic nervous system in patients with COPD. SSRs were recorded in 30 patients with COPD and 21 healthy volunteers. Normal responses were obtained from all subjects in the control group. No response was observed in three patients with COPD. The mean latency, amplitude and area values of the potentials recorded of the remaining 27 patients were compared to the control. The mean latency was longer (p<0.01) and the mean amplitude and area values were lower (p=0.012, p=0.021, respectively) in the patients compared to the control. We also demonstrated significant correlations between the latency, amplitude, or area values of the SSR and two parameters of pulmonary function tests forced expiratory volume one second/forced vital capacity (FEV1/FVC) and FEV1/FVC %. In conclusion, SSR is impaired in patients with COPD, which indicates the dysfunction of the sympathetic nervous system. Furthermore, the degree of impairment in SSR may reflect the severity of airway obstruction in patients with COPD. PMID:16272793

  10. The pollen enigma: modulation of the allergic immune response by non-allergenic, pollen-derived compounds.

    PubMed

    Gilles, Stefanie; Behrendt, Heidrun; Ring, Johannes; Traidl-Hoffmann, Claudia

    2012-01-01

    The question what makes an allergen an allergen puzzled generations of researchers. Pollen grains of anemophilous plants are the most important allergen carriers in ambient air, and pollinosis is a highly prevalent multi-organ disease in civilized countries. In the past, research on the allergenicity of pollen has mainly focused on elucidating genetic predisposing factors and on defining certain structural characteristics of pollen derived allergens. Recently, studies extended to the analysis of non-allergenic, adjuvant mediators co-released from pollen. Besides active proteases and oxidases, extracts of pollen contain low molecular weight molecules like pollen-associated lipid mediators or adenosine exhibiting a potential to stimulate and modulate cultured human immune cells. This article reviews our current knowledge on non-allergenic, protein and non-protein compounds from pollen and their in vitro and in vivo effects on the allergic immune response. To ultimately judge the physiological relevance of these compounds, a systematic approach will be needed comparing their releasability, content and activity in different, allergenic and non-allergenic, pollen species. System biology such as proteome and metabolome analysis will be a useful future approach to better understand pollen biology. PMID:22390694

  11. The major birch pollen allergen Bet v 1 induces different responses in dendritic cells of birch pollen allergic and healthy individuals.

    PubMed

    Smole, Ursula; Radauer, Christian; Lengger, Nina; Svoboda, Martin; Rigby, Neil; Bublin, Merima; Gaier, Sonja; Hoffmann-Sommergruber, Karin; Jensen-Jarolim, Erika; Mechtcheriakova, Diana; Breiteneder, Heimo

    2015-01-01

    Dendritic cells play a fundamental role in shaping the immune response to allergens. The events that lead to allergic sensitization or tolerance induction during the interaction of the major birch pollen allergen Bet v 1 and dendritic cells are not very well studied. Here, we analyzed the uptake of Bet v 1 and the cross-reactive celery allergen Api g 1 by immature monocyte-derived dendritic cells (iMoDCs) of allergic and normal donors. In addition, we characterized the allergen-triggered intracellular signaling and transcriptional events. Uptake kinetics, competitive binding, and internalization pathways of labeled allergens by iMoDCs were visualized by live-cell imaging. Surface-bound IgE was detected by immunofluorescence microscopy and flow cytometry. Allergen- and IgE-induced gene expression of early growth response genes and Th1 and Th2 related cytokines and chemokines were analyzed by real-time PCR. Phosporylation of signaling kinases was analyzed by Western blot. Internalization of Bet v 1 by iMoDCs of both donor groups, likely by receptor-mediated caveolar endocytosis, followed similar kinetics. Bet v 1 outcompeted Api g 1 in cell surface binding and uptake. MoDCs of allergic and healthy donors displayed surface-bound IgE and showed a pronounced upregulation of Th2 cytokine- and NFκB-dependent genes upon non-specific Fcε receptor cross-linking. In contrast to these IgE-mediated responses, Bet v 1-stimulation increased transcript levels of the Th2 cytokines IL-4 and IL-13 but not of NFκB-related genes in MoDCs of BP allergic donors. Cells of healthy donors were either unresponsive or showed elevated mRNA levels of Th1-promoting chemokines. Moreover, Bet v 1 was able to induce Erk1/2 and p38 MAPK activation in BP allergics but only a slight p38 activation in normal donors. In conclusion, our data indicate that Bet v 1 favors the activation of a Th2 program only in DCs of BP allergic individuals. PMID:25635684

  12. The Major Birch Pollen Allergen Bet v 1 Induces Different Responses in Dendritic Cells of Birch Pollen Allergic and Healthy Individuals

    PubMed Central

    Smole, Ursula; Radauer, Christian; Lengger, Nina; Svoboda, Martin; Rigby, Neil; Bublin, Merima; Gaier, Sonja; Hoffmann-Sommergruber, Karin; Jensen-Jarolim, Erika; Mechtcheriakova, Diana; Breiteneder, Heimo

    2015-01-01

    Dendritic cells play a fundamental role in shaping the immune response to allergens. The events that lead to allergic sensitization or tolerance induction during the interaction of the major birch pollen allergen Bet v 1 and dendritic cells are not very well studied. Here, we analyzed the uptake of Bet v 1 and the cross-reactive celery allergen Api g 1 by immature monocyte-derived dendritic cells (iMoDCs) of allergic and normal donors. In addition, we characterized the allergen-triggered intracellular signaling and transcriptional events. Uptake kinetics, competitive binding, and internalization pathways of labeled allergens by iMoDCs were visualized by live-cell imaging. Surface-bound IgE was detected by immunofluorescence microscopy and flow cytometry. Allergen- and IgE-induced gene expression of early growth response genes and Th1 and Th2 related cytokines and chemokines were analyzed by real-time PCR. Phosporylation of signaling kinases was analyzed by Western blot. Internalization of Bet v 1 by iMoDCs of both donor groups, likely by receptor-mediated caveolar endocytosis, followed similar kinetics. Bet v 1 outcompeted Api g 1 in cell surface binding and uptake. MoDCs of allergic and healthy donors displayed surface-bound IgE and showed a pronounced upregulation of Th2 cytokine- and NFκB-dependent genes upon non-specific Fcε receptor cross-linking. In contrast to these IgE-mediated responses, Bet v 1-stimulation increased transcript levels of the Th2 cytokines IL-4 and IL-13 but not of NFκB-related genes in MoDCs of BP allergic donors. Cells of healthy donors were either unresponsive or showed elevated mRNA levels of Th1-promoting chemokines. Moreover, Bet v 1 was able to induce Erk1/2 and p38 MAPK activation in BP allergics but only a slight p38 activation in normal donors. In conclusion, our data indicate that Bet v 1 favors the activation of a Th2 program only in DCs of BP allergic individuals. PMID:25635684

  13. Effects of Lactobacillus rhamnosus on allergic march model by suppressing Th2, Th17, and TSLP responses via CD4(+)CD25(+)Foxp3(+) Tregs.

    PubMed

    Kim, Ha-Jung; Kim, Young-Joon; Lee, Seung-Hwa; Yu, Jinho; Jeong, Se Kyoo; Hong, Soo-Jong

    2014-07-01

    Allergic march (AM) is characterized by the progression of clinical signs of atopic dermatitis (AD) to allergic asthma or rhinitis, but its pathogenesis is not completely understood. We developed mouse model of AM with three 1-week exposures (separated by 2-week interval) to an OVA or saline (control) followed by OVA challenge. The development of AM was confirmed by phenotypes of AD and allergic asthma. Increases in IL-4, IL-17, and thymic stromal lymphopoietin (TSLP) responses were associated with the progression of AM, and these responses were suppressed by treatment with Lcr35. Moreover, Lcr35 treatment led to an increase in the number of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells in the mesenteric lymph nodes (MLNs) of AM mice. In conclusion, the oral application of Lcr35 prevented the development of AM in this model by suppressing Th2, Th17, and TSLP responses via a mechanism that may involve CD4(+)CD25(+)Foxp3(+) Tregs in MLNs. PMID:24769377

  14. Projecting sensations to external objects: evidence from skin conductance response.

    PubMed Central

    Armel, K Carrie; Ramachandran, V S

    2003-01-01

    Subjects perceived touch sensations as arising from a table (or a rubber hand) when both the table (or the rubber hand) and their own real hand were repeatedly tapped and stroked in synchrony with the real hand hidden from view. If the table or rubber hand was then 'injured', subjects displayed a strong skin conductance response (SCR) even though nothing was done to the real hand. Sensations could even be projected to anatomically impossible locations. The illusion was much less vivid, as indicated by subjective reports and SCR, if the real hand was simultaneously visible during stroking, or if the real hand was hidden but touched asynchronously. The fact that the illusion could be significantly diminished when the real hand was simultaneously visible suggests that the illusion and associated SCRs were due to perceptual assimilation of the table (or rubber hand) into one's body image rather than associative conditioning. These experiments demonstrate the malleability of body image and the brain's remarkable capacity for detecting statistical correlations in the sensory input. PMID:12965016

  15. Environment and the skin.

    PubMed

    Suskind, R R

    1977-10-01

    The skin is an important interface between man and his environment; it is an important portal of entry for hazardous agents and a vulnerable target tissue as well. It is a uniquely accessible model system for detecting hazards and for studying mechanisms of a wide variety of biologic funcitons. Environmental causes of skin reactions comprise a vast array of physical, chemical and biological agents. To appreciate the role of the skin as an interface with man's environment, it is necessary to understand the multiple adaptive mechanisms, and the defenses of the skin against the environmental stresses. The skin is endowed with a versatile group of defenses against penetration, fluid loss from the body, thermal stress, solar radiation, physical trauma and microbial agents. Patterns of adverse response range in quality and intensity from uncomplicated itching to metastatic neoplasia. Environmental problems comprise a large segment of disabling skin disease. Although critical epidemiologic data is limited, cutaneous illnesses comprise a significant segment of occupational disease. This represents a significant loss in productivity and a major cause of disability. The most serious research needs include the development of surveillance systems for identifying skin hazards and determining frequency of environmental skin disease; the development of new models for studying cutaneous penetration; the elucidation of the mechanisms of nonallergic inflammatory reactions (primary irritation) and of the accommodation phenomenon; the development of more sensitive models for predicting adverse responses to marginal irritants; the utilization of modern skills of immunobiology and immunochemistry to elucidate mechanisms of allergic responses; the launching of epidemiologic studies to determine the long term effects of PCBs and associated compounds such as dioxins; and the expansion of research in the mechanisms of skin cancer in relation to susceptibility, genetic and metabolic

  16. Environment and the skin

    PubMed Central

    Suskind, Raymond R.

    1977-01-01

    The skin is an important interface between man and his environment; it is an important portal of entry for hazardous agents and a vulnerable target tissue as well. It is a uniquely accessible model system for detecting hazards and for studying mechanisms of a wide variety of biologic funcitons. Environmental causes of skin reactions comprise a vast array of physical, chemical and biological agents. To appreciate the role of the skin as an interface with man's environment, it is necessary to understand the multiple adaptive mechanisms, and the defenses of the skin against the environmental stresses. The skin is endowed with a versatile group of defenses against penetration, fluid loss from the body, thermal stress, solar radiation, physical trauma and microbial agents. Patterns of adverse response range in quality and intensity from uncomplicated itching to metastatic neoplasia. Environmental problems comprise a large segment of disabling skin disease. Although critical epidemiologic data is limited, cutaneous illnesses comprise a significant segment of occupational disease. This represents a significant loss in productivity and a major cause of disability. The most serious research needs include the development of surveillance systems for identifying skin hazards and determining frequency of environmental skin disease; the development of new models for studying cutaneous penetration; the elucidation of the mechanisms of nonallergic inflammatory reactions (primary irritation) and of the accommodation phenomenon; the development of more sensitive models for predicting adverse responses to marginal irritants; the utilization of modern skills of immunobiology and immunochemistry to elucidate mechanisms of allergic responses; the launching of epidemiologic studies to determine the long term effects of PCBs and associated compounds such as dioxins; and the expansion of research in the mechanisms of skin cancer in relation to susceptibility, genetic and metabolic

  17. Local allergic rhinitis: A critical reappraisal from a paediatric perspective.

    PubMed

    Arasi, Stefania; Pajno, Giovanni Battista; Lau, Susanne; Matricardi, Paolo Maria

    2016-09-01

    The so-called local allergic rhinitis (LAR) has been proposed as a phenotype of rhinitis with Th2-driven prominent local allergic inflammation, nasal synthesis of specific IgE and a positive response to a nasal allergen provocation test, in the absence of 'systemic' atopy (negative skin prick test and serum allergen-specific IgE antibodies). To date, available data on LAR are mostly focused on adults. The purpose of this 'Rostrum' was to critically discuss data and implications of the 'LAR concept' in paediatrics. In the natural history of rhinitis due to IgE-mediated reactions triggered by exposure to allergens, a 'LAR' can be either the initial, transient stage of classical allergic rhinitis or a stable phenotype never evolving to 'systemic' IgE sensitization. Given the present difficulties in performing routinely nasal allergen provocation test in children, the development of sensitive and specific tests to detect IgE in the child's nasal secretions is a research priority. We suggest also the hypothetical role of allergen immunoprophylaxis or immunotherapy in LAR. Last, the term 'local allergic rhinitis' may be inappropriate, as rhinitis is always 'local', while IgE sensitization can be either 'local' or 'systemic'. PMID:27098888

  18. Human skin pigmentation: melanocytes modulate skin color in response to stress.

    PubMed

    Costin, Gertrude-E; Hearing, Vincent J

    2007-04-01

    All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from the unique distribution of pigments throughout the body. Pigmentation is highly heritable, being regulated by genetic, environmental, and endocrine factors that modulate the amount, type, and distribution of melanins in the skin, hair, and eyes. In addition to its roles in camouflage, heat regulation, and cosmetic variation, melanin protects against UV radiation and thus is an important defense system in human skin against harmful factors. Being the largest organ of the body that is always under the influence of internal and external factors, the skin often reacts to those agents by modifying the constitutive pigmentation pattern. The focus of this review is to provide an updated overview of important physiological and biological factors that increase pigmentation and the mechanisms by which they do so. We consider endocrine factors that induce temporary (e.g., during pregnancy) or permanent (e.g., during aging) changes in skin color, environmental factors (e.g., UV), certain drugs, and chemical compounds, etc. Understanding the mechanisms by which different factors and compounds induce melanogenesis is of great interest pharmaceutically (as therapy for pigmentary diseases) and cosmeceutically (e.g., to design tanning products with potential to reduce skin cancer risk). PMID:17242160

  19. Langerhans cells in allergic contact dermatitis.

    PubMed

    Tuchinda, P; Gaspari, A A

    2010-12-01

    Allergic contact dermatitis (ACD) is a common skin disease that has significant socio-economic impact. ACD is mediated by a T-cell mediated inflammatory reaction. Langerhans cells (LCs) are an epidermal DCs subset specialized in antigen presentation. After hapten exposure, LCs play a major role as in induction adaptive immune response against allergens. LCs recognize, take up and process haptens and migrate to the local draining lymph nodes. However, LCs specific functions and the LCs migration to local draining lymph nodes are not yet clearly defined. Recent advance in the knowledge of LCs function has increased in the past decades including the evidence for a tolerogenic function of LCs. The present review will focus on the role for LCs response to contact allergens. PMID:21139551

  20. Mucosal delivery of allergen peptides expressed by Lactococcus lactis inhibit allergic responses in a BALB/c mouse model.

    PubMed

    Ai, Chunqing; Zhang, Qiuxiang; Ding, Junrong; Wang, Gang; Liu, Xiaoming; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Chen, Wei

    2016-02-01

    Allergen-specific immunotherapy (SIT) is considered to be the only curative treatment of allergy, but its safety is always affected by immunologic properties and quality of allergen. Recombinant allergen derivative could be a potential therapeutic strategy, but clinical studies showed that macromolecular derivatives could not avoid T cell-mediated side effects. In this study, five Der p2-derived peptides (DPs) containing major T cell epitopes of Der p2 were first artificially synthesized. Compared with Der p2 macromolecular derivative DM, these DPs not only fully eliminated IgE-binding capacity but also reduced T cells reactivity, suggesting these DPs could be better therapeutic molecules. For their application in vivo, Lactococcus lactis was engineered to express these DPs, and their protective effects were evaluated in BALB/c mice models. Western blot showed that all DPs could be produced in the recombinant strains. Mucosal delivery of these strains could inhibit Der p2-induced allergic responses in Der p2-sensitized mice, characterized by a reduction in specific IgE antibody and lung inflammatory responses. These protective effects were associated with an increase of specific IgG2a in serum and regulatory T cells in the mesenteric lymph nodes. On the whole, the suppressive effect induced by the DP mixture could be better than single DP, but a bit weaker than DM. These DPs could be promising candidate molecules for active vaccination and induction of tolerance, and thus promote the development of non-allergenic peptide in the treatment and prevention of allergy. PMID:26621801

  1. Distribution of T Cells in Rainbow Trout (Oncorhynchus mykiss) Skin and Responsiveness to Viral Infection

    PubMed Central

    Leal, Esther; Granja, Aitor G.; Zarza, Carlos; Tafalla, Carolina

    2016-01-01

    Although the skin constitutes the first line of defense against waterborne pathogens, there is a great lack of information regarding the skin associated lymphoid tissue (SALT) and whether immune components of the skin are homogeneously distributed through the surface of the fish is still unknown. In the current work, we have analyzed the transcription of several immune genes throughout different rainbow trout (Oncorhynchus mykiss) skin areas. We found that immunoglobulin and chemokine gene transcription levels were higher in a skin area close to the gills. Furthermore, this skin area as well as other anterior sections also transcribed significantly higher levels of many different immune genes related to T cell immunity such as T cell receptor α (TCRα), TCRγ, CD3, CD4, CD8, perforin, GATA3, Tbet, FoxP3, interferon γ (IFNγ), CD40L and Eomes in comparison to posterior skin sections. In agreement with these results, immunohistochemical analysis revealed that anterior skin areas had a higher concentration of CD3+ T cells and flow cytometry analysis confirmed that the percentage of CD8+ T lymphocytes was also higher in anterior skin sections. These results demonstrate for the first time that T cells are not homogeneously distributed throughout the teleost skin. Additionally, we studied the transcriptional regulation of these and additional T cell markers in response to a bath infection with viral hemorrhagic septicemia virus (VHSV). We found that VHSV regulated the transcription of several of these T cell markers in both the skin and the spleen; with some differences between anterior and posterior skin sections. Altogether, our results point to skin T cells as major players of teleost skin immunity in response to waterborne viral infections. PMID:26808410

  2. Distribution of T Cells in Rainbow Trout (Oncorhynchus mykiss) Skin and Responsiveness to Viral Infection.

    PubMed

    Leal, Esther; Granja, Aitor G; Zarza, Carlos; Tafalla, Carolina

    2016-01-01

    Although the skin constitutes the first line of defense against waterborne pathogens, there is a great lack of information regarding the skin associated lymphoid tissue (SALT) and whether immune components of the skin are homogeneously distributed through the surface of the fish is still unknown. In the current work, we have analyzed the transcription of several immune genes throughout different rainbow trout (Oncorhynchus mykiss) skin areas. We found that immunoglobulin and chemokine gene transcription levels were higher in a skin area close to the gills. Furthermore, this skin area as well as other anterior sections also transcribed significantly higher levels of many different immune genes related to T cell immunity such as T cell receptor α (TCRα), TCRγ, CD3, CD4, CD8, perforin, GATA3, Tbet, FoxP3, interferon γ (IFNγ), CD40L and Eomes in comparison to posterior skin sections. In agreement with these results, immunohistochemical analysis revealed that anterior skin areas had a higher concentration of CD3(+) T cells and flow cytometry analysis confirmed that the percentage of CD8(+) T lymphocytes was also higher in anterior skin sections. These results demonstrate for the first time that T cells are not homogeneously distributed throughout the teleost skin. Additionally, we studied the transcriptional regulation of these and additional T cell markers in response to a bath infection with viral hemorrhagic septicemia virus (VHSV). We found that VHSV regulated the transcription of several of these T cell markers in both the skin and the spleen; with some differences between anterior and posterior skin sections. Altogether, our results point to skin T cells as major players of teleost skin immunity in response to waterborne viral infections. PMID:26808410

  3. PHENOTYPIC COMPARISON OF ALLERGIC AIRWAY RESPONSES TO HOUSE DUST MITE IN THREE RAT STRAINS

    EPA Science Inventory

    Abstract
    Brown Norway (BN) rats develop a robust response to antigens in the lung characterized by a large increase in allergen-specific immune function and pulmonary eosinophilia. The objective of this study was to investigate alternative models by determining if other rat s...

  4. Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond

    PubMed Central

    Graham, Amy C.; Temple, Rachel M.; Obar, Joshua J.

    2015-01-01

    Influenza A virus (IAV) is a widespread infectious agent commonly found in mammalian and avian species. In humans, IAV is a respiratory pathogen that causes seasonal infections associated with significant morbidity in young and elderly populations, and has a large economic impact. Moreover, IAV has the potential to cause both zoonotic spillover infection and global pandemics, which have significantly greater morbidity and mortality across all ages. The pathology associated with these pandemic and spillover infections appear to be the result of an excessive inflammatory response leading to severe lung damage, which likely predisposes the lungs for secondary bacterial infections. The lung is protected from pathogens by alveolar epithelial cells, endothelial cells, tissue resident alveolar macrophages, dendritic cells, and mast cells. The importance of mast cells during bacterial and parasitic infections has been extensively studied; yet, the role of these hematopoietic cells during viral infections is only beginning to emerge. Recently, it has been shown that mast cells can be directly activated in response to IAV, releasing mediators such histamine, proteases, leukotrienes, inflammatory cytokines, and antiviral chemokines, which participate in the excessive inflammatory and pathological response observed during IAV infections. In this review, we will examine the relationship between mast cells and IAV, and discuss the role of mast cells as a potential drug target during highly pathological IAV infections. Finally, we proposed an emerging role for mast cells in other viral infections associated with significant host pathology. PMID:26042121

  5. Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis

    PubMed Central

    Kumagai, Kenichi; Horikawa, Tatsuya; Shigematsu, Hiroaki; Matsubara, Ryota; Kitaura, Kazutaka; Eguchi, Takanori; Kobayashi, Hiroshi; Nakasone, Yasunari; Sato, Koichiro; Yamada, Hiroyuki; Suzuki, Satsuki; Hamada, Yoshiki; Suzuki, Ryuji

    2016-01-01

    Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion–induced allergic contact dermatitis. PMID:26771600

  6. Allergy testing - skin

    MedlinePlus

    ... if you are allergic to bee venom or penicillin. Or it may be used if the skin ... sore, or swollen after contact with the substance Penicillin allergy Venom allergy Allergies to penicillin and closely ...

  7. 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

  8. Basic Taste Stimuli Elicit Unique Responses in Facial Skin Blood Flow

    PubMed Central

    Kashima, Hideaki; Hayashi, Naoyuki

    2011-01-01

    Facial expression changes characteristically with the emotions induced by basic tastes in humans. We tested the hypothesis that the five basic tastes also elicit unique responses in facial skin blood flow. Facial skin blood flow was measured using laser speckle flowgraphy in 16 healthy subjects before and during the application of basic taste stimuli in the oral cavity for 20 s. The skin blood flow in the eyelid increased in response to sweet and umami taste stimuli, while that in the nose decreased in response to a bitter stimulus. There was a significant correlation between the subjective hedonic scores accompanying these taste stimuli and the above changes in skin blood flow. These results demonstrate that sweet, umami, and bitter tastes induce unique changes in facial skin blood flow that reflect subjective hedonic scores. PMID:22145032

  9. Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation.

    PubMed

    Cardoso, L S; Oliveira, S C; Góes, A M; Oliveira, R R; Pacífico, L G; Marinho, F V; Fonseca, C T; Cardoso, F C; Carvalho, E M; Araujo, M I

    2010-05-01

    Schistosoma mansoni infection has been associated with protection against allergies. The mechanisms underlying this association may involve regulatory cells and cytokines. We evaluated the immune response induced by the S. mansoni antigens Sm22.6, PIII and Sm29 in a murine model of ovalbumin (OVA)-induced airway inflammation. BALB/c mice were sensitized with subcutaneously injected OVA-alum and challenged with aerolized OVA. Mice were given three doses of the different S. mansoni antigens. Lung histopathology, cellularity of bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in lung were evaluated. Immunoglobulin (Ig)E levels in serum and cytokines in BAL were also measured. Additionally, we evaluated the frequency of CD4+forkhead box P3 (FoxP3)+ T cells in cultures stimulated with OVA and the expression of interleukin (IL)-10 by these cells. The number of total cells and eosinophils in BAL and the levels of OVA-specific IgE were reduced in the immunized mice. Also, the levels of IL-4 and IL-5 in the BAL of mice immunized with PIII and Sm22.6 were decreased, while the levels of IL-10 were higher in mice immunized with Sm22.6 compared to the non-immunized mice. The frequency of CD4+FoxP3+ T cells was higher in the groups of mice who received Sm22.6, Sm29 and PIII, being the expression of IL-10 by these cells only higher in mice immunized with Sm22.6. We concluded that the S. mansoni antigens used in this study are able to down-modulate allergic inflammatory mediators in a murine model of airway inflammation and that the CD4+FoxP3+ T cells, even in the absence of IL-10 expression, might play an important role in this process. PMID:20132231

  10. Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation

    PubMed Central

    Cardoso, L S; Oliveira, S C; Góes, A M; Oliveira, R R; Pacífico, L G; Marinho, F V; Fonseca, C T; Cardoso, F C; Carvalho, E M; Araujo, M I

    2010-01-01

    Schistosoma mansoni infection has been associated with protection against allergies. The mechanisms underlying this association may involve regulatory cells and cytokines. We evaluated the immune response induced by the S. mansoni antigens Sm22·6, PIII and Sm29 in a murine model of ovalbumin (OVA)-induced airway inflammation. BALB/c mice were sensitized with subcutaneously injected OVA-alum and challenged with aerolized OVA. Mice were given three doses of the different S. mansoni antigens. Lung histopathology, cellularity of bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in lung were evaluated. Immunoglobulin (Ig)E levels in serum and cytokines in BAL were also measured. Additionally, we evaluated the frequency of CD4+forkhead box P3 (FoxP3)+ T cells in cultures stimulated with OVA and the expression of interleukin (IL)-10 by these cells. The number of total cells and eosinophils in BAL and the levels of OVA-specific IgE were reduced in the immunized mice. Also, the levels of IL-4 and IL-5 in the BAL of mice immunized with PIII and Sm22·6 were decreased, while the levels of IL-10 were higher in mice immunized with Sm22·6 compared to the non-immunized mice. The frequency of CD4+FoxP3+ T cells was higher in the groups of mice who received Sm22·6, Sm29 and PIII, being the expression of IL-10 by these cells only higher in mice immunized with Sm22·6. We concluded that the S. mansoni antigens used in this study are able to down-modulate allergic inflammatory mediators in a murine model of airway inflammation and that the CD4+FoxP3+ T cells, even in the absence of IL-10 expression, might play an important role in this process. PMID:20132231

  11. T cell-derived Act1 is necessary for IL-25-mediated Th2 responses and allergic airway inflammation.

    PubMed

    Swaidani, Shadi; Bulek, Katarzyna; Kang, Zizhen; Gulen, Muhammet Fatih; Liu, Caini; Yin, Weiguo; Abbadi, Amina; Aronica, Mark; Li, Xiaoxia

    2011-09-15

    The cellular and molecular mechanisms driven by IL-25 and its cognate receptor IL-17RB necessary for the promotion of Th2-mediating pathogenic pulmonary inflammation remains to be defined. We have previously reported the critical role of the U-box-type E3 ubiquitin ligase Act1 (1) for the downstream signaling of the IL-17 cytokine family including the Th2-promoting cytokine IL-25 (IL-17E) (2). In this study, we report that IL-25-driven but not conventional IL-4-driven Th2 polarization and cytokine production is impaired in Act1-deficient T cells. Also, Act1 deficiency in the T cell compartment results in the abrogation of eosinophilic airway infiltration as well as airway hyperresponsiveness in mouse models of Ag-induced airway inflammation. The in vivo generation of Ag-specific Th2 cytokine-producing cells is defective in the absence of Act1 expression in T cells after OVA/aluminum hydroxide immunization. Notably, the production of OVA-specific IgG(1) but not IgG(2a) or IgE is also impaired. At the molecular level, we report that IL-25-mediated induction of Th2 master regulator GATA-3 and the transcription factor GFI-1 is attenuated in Act1-deficient T cells. Taken together, our findings indicate that Act1 expression in T cells is required for cellular and humoral Th2-mediated allergic responses and the development of airway hyperresponsiveness, in part, through Act1's function in IL-25-induced development of Th2 T cells. PMID:21856933

  12. Peanut proteins in periodate specific anion sensing: An ensuing reduction in allergic response.

    PubMed

    Ghatak, Sumanta Kumar; Sen, Souvik; Majumdar, Dipanwita; Singha, Achintya; Sen, Kamalika

    2016-04-15

    Peanut proteins conarachin II, conarachin I and arachin were found to behave as highly selective fluorescence sensors for periodate amongst a set of different anions. The interactions of the proteins with periodate were also confirmed by other spectral methods and enzyme linked immunosorbent assay (ELISA). The results indicate a selective interaction of peanut proteins with periodate amongst chloride, sulphate, iodide, phosphate, nitrate, nitrite, bromide, fluoride, persulphate, acetate, thiosulphate, arsenite, arsenate, sulphite, and iodide. Periodate sensing using different synthesized organic molecules are already reported in the literature. In this article we report the efficiency of peanut proteins as anion sensor which are bioactive and inexpensive too. The protein periodate interactions have also resulted in a simultaneous reduction in allergenicity of the peanut proteins. A change in the secondary structure of the protein was found responsible for this change which was further established with the help of circular dichroism and Raman spectroscopy. PMID:26675870

  13. Allergic airway disease in Italian bakers and pastry makers.

    PubMed Central

    De Zotti, R; Larese, F; Bovenzi, M; Negro, C; Molinari, S

    1994-01-01

    A survey was carried out on respiratory symptoms and skin prick test response to common allergens (atopy), storage mites, and occupational allergens among 226 bakers and pastry makers from 105 small businesses in northern Italy. Atopy was present in 54 workers (23.4%); 40 workers (17.7%) were skin positive to at least one storage mite, 27 (11.9%) to wheat flour and 17 (7.5%) to alpha-amylase. Work related asthma was reported by 11 (4.9%) workers and rhinoconjunctivitis by 31 (17.7%); 22 workers (10.2%) complained of chronic bronchitis. The distribution of skin prick test results among bakers and among 119 white collar workers did not indicate (by logistic analysis) an increased risk for bakers to skin sensitisation to common allergens, storage mite, or to a group of five flours. Sensitisation to wheat flour, on the other hand, was present only among exposed workers. Skin sensitisation to occupational allergens was significantly associated with atopy (p < 0.001), smoking habit (p = 0.015), and work seniority (p = 0.027). The risk of work related symptoms was associated with sensitisation to wheat or alpha-amylase, and with atopy, but not with sensitisation to storage mites, work seniority, or smoking habit. The results of the study indicate that there is still a significant risk of allergic respiratory disease among Italian bakers. Not only wheat allergens, but also alpha-amylase must be considered as causative agents, although sensitisation to storage mites is not important in the occupational allergic response. Atopy must be regarded as an important predisposing factor for skin sensitisation to occupational allergens and for the onset of symptoms at work. The data confirm that for effective prevention, greater care should be taken not only in limiting environmental exposure, but also in identifying susceptible people. PMID:7951780

  14. 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

  15. Epithelial Cell Regulation of Allergic Diseases.

    PubMed

    Gour, Naina; Lajoie, Stephane

    2016-09-01

    Allergic diseases, which have escalated in prevalence in recent years, arise as a result of maladaptive immune responses to ubiquitous environmental stimuli. Why only certain individuals mount inappropriate type 2 immune responses to these otherwise harmless allergens has remained an unanswered question. Mounting evidence suggests that the epithelium, by sensing its environment, is the central regulator of allergic diseases. Once considered to be a passive barrier to allergens, epithelial cells at mucosal surfaces are now considered to be the cornerstone of the allergic diathesis. Beyond their function as maintaining barrier at mucosal surfaces, mucosal epithelial cells through the secretion of mediators like IL-25, IL-33, and TSLP control the fate of downstream allergic immune responses. In this review, we will discuss the advances in recent years regarding the process of allergen recognition and secretion of soluble mediators by epithelial cells that shape the development of the allergic response. PMID:27534656

  16. Effect of skin temperature on cutaneous vasodilator response to the β-adrenergic agonist isoproterenol

    PubMed Central

    Hodges, Gary J.; Johnson, John M.

    2015-01-01

    The vascular response to local skin cooling is dependent in part on a cold-induced translocation of α2C-receptors and an increased α-adrenoreceptor function. To discover whether β-adrenergic function might contribute, we examined whether β-receptor sensitivity to the β-agonist isoproterenol was affected by local skin temperature. In seven healthy volunteers, skin blood flow was measured from the forearm by laser-Doppler flowmetry and blood pressure was measured by finger photoplethysmography. Data were expressed as cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial blood pressure). Pharmacological agents were administered via intradermal microdialysis. We prepared four skin sites: one site was maintained at a thermoneutral temperature of 34°C (32 ± 10%CVCmax) one site was heated to 39°C (38 ± 11%CVCmax); and two sites were cooled, one to 29°C (22 ± 7%CVCmax) and the other 24°C (16 ± 4%CVCmax). After 20 min at these temperatures to allow stabilization of skin blood flow, isoproterenol was perfused in concentrations of 10, 30, 100, and 300 μM. Each concentration was perfused for 15 min. Relative to the CVC responses to isoproterenol at the thermoneutral skin temperature (34°C) (+21 ± 10%max), low skin temperatures reduced (at 29°C) (+17 ± 6%max) or abolished (at 24°C) (+1 ± 5%max) the vasodilator response, and warm (39°C) skin temperatures enhanced the vasodilator response (+40 ± 9%max) to isoproterenol. These data indicate that β-adrenergic function was influenced by local skin temperature. This finding raises the possibility that a part of the vasoconstrictor response to direct skin cooling could include reduced background β-receptor mediated vasodilation. PMID:25701007

  17. TIMING OF DIESEL PARTICLE INSTILLATION AND MAGNITUDE OF DOSE INFLUENCE THE SEVERITY OF ALLERGIC AIRWAYS RESPONSES IN MICE

    EPA Science Inventory

    Exposure to diesel exhaust particulates (DEP) arising from the combustion of diesel fuel exacerbates asthma. Several studies have shown that particulate and allergen co-exposure leads to an exacerbation of the hallmark features of allergic airways disease relative to allergen exp...

  18. Comparison of the Allergic Responses Induced by PeniciIlium chrysogenum and House Dust Mite Extracts in a Mouse Model

    EPA Science Inventory

    A report by the Institute of Medicine suggested that more research is needed to better understand mold effects on allergic disease, particularly asthma development. We compared the ability of the fungal Penicillium chrysogenum (PCE) and house dust mite (HDM) extracts to induce al...

  19. Update on local allergic rhinitis.

    PubMed

    Altıntoprak, Niyazi; Kar, Murat; Bayar Muluk, Nuray; Oktemer, Tugba; Ipci, Kagan; Birdane, Leman; Aricigil, Mitat; Senturk, Mehmet; Bafaqeeh, Sameer Ali; Cingi, Cemal

    2016-08-01

    We here provide an update on the literature regarding local allergic rhinitis (LAR). In reviewing LAR, we have included an updated definition, classifications, mechanisms, comorbidities, and recommendations for diagnosis and treatment for LAR, as well as the defined research areas for future evidence-based studies. LAR is a localised nasal allergic response in the absence of systemic atopy characterised by local production of specific IgE (sIgE) antibodies, a TH2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response, with the release of inflammatory mediators. The localised allergic response of LAR is an important topic for the study of allergies. This review provides an update on the current knowledge of LAR. PMID:27368453

  20. Allergic responses to the biopesticide Metarhizium anisopliae in Balb/c mice.

    PubMed

    Ward, M D; Sailstad, D M; Selgrade, M K

    1998-10-01

    Metarhizium anisopliae is used as a microbial pesticide to control cockroaches and other insects. M. anisopliae has demonstrated neither infectivity nor toxicity in mammals. However, allergenicity has not been assessed. M. anisopliae is a prototype for other organisms released into the environment for pesticide or other beneficial applications. Hence this study is part of an effort to develop methods for screening such organisms for allergenic potential. Soluble factors from fungal components were combined in equal protein amounts to form a crude fungal antigen (MACA). Balb/c mice were intratracheally (IT) challenged with 25 micrograms fungal antigen 13 days post intraperitoneal sensitization with the fungal antigen in alhydrogel adjuvant. Additionally, mice were sensitized with adjuvant alone or chitin media in adjuvant as experimental controls. Serum and bronchoalveolar lavage fluid (BALF) were harvested prior to challenge and at 1 and 7 days post IT challenge (DPIT). These mice exhibited immune and pulmonary inflammatory responses to MACA characteristic of allergy. Total serum IgE for antigen-sensitized animals increased 7.6- and 14.7-fold over that for chitin media and adjuvant controls, respectively, at 7 DPIT. Less striking increases were seen at 24 DPIT and prior to challenge. BALF IL-4 was dramatically elevated only in MACA-sensitized and challenged mice and only at 1 DPIT. Additionally, there was a dose-dependent increase in BALF eosinophils from MACA-sensitized mice at both 1 and 7 DPIT. While lymphocyte counts were increased for all treatment groups at 1 DPIT, by 7 DPIT lymphocyte counts for MACA-sensitized mice only were significantly elevated compared to controls. Pulmonary inflammation, edema, and cell damage were apparent at 1 DPIT (25 micrograms MACA), as indicated by a neutrophilic influx and elevated levels of total protein and LDH, in both sensitized and control groups. These effects were significantly decreased, but not eliminated by reduction

  1. Basophils and allergic inflammation.

    PubMed

    Siracusa, Mark C; Kim, Brian S; Spergel, Jonathan M; Artis, David

    2013-10-01

    Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in human subjects and murine systems have shown that basophils perform nonredundant effector functions and significantly contribute to the development and progression of TH2 cytokine-mediated inflammation. Although the potential functions of murine and human basophils have provoked some controversy, recent genetic approaches indicate that basophils can migrate into lymphoid tissues and, in some circumstances, cooperate with other immune cells to promote optimal TH2 cytokine responses in vivo. This article provides a brief historical perspective on basophil-related research and discusses recent studies that have identified previously unappreciated molecules and pathways that regulate basophil development, activation, and function in the context of allergic inflammation. Furthermore, we highlight the unique effector functions of basophils and discuss their contributions to the development and pathogenesis of allergic inflammation in human disease. Finally, we discuss the therapeutic potential of targeting basophils in preventing or alleviating the development and progression of allergic inflammation. PMID:24075190

  2. Attenuation of IgE Affinity for FcεRI Radically Reduces the Allergic Response in Vitro and in Vivo*

    PubMed Central

    Hunt, James; Bracher, Marguerite G.; Shi, Jianguo; Fleury, Sébastien; Dombrowicz, David; Gould, Hannah J.; Sutton, Brian J.; Beavil, Andrew J.

    2008-01-01

    The high affinity of IgE for its receptor, FcεRI (Ka ∼ 1010 m–1), is responsible for the persistence of mast cell sensitization. Cross-linking of FcεRI-bound IgE by multivalent allergen leads to cellular activation and release of pro-inflammatory mediators responsible for the symptoms of allergic disease. We previously demonstrated that limiting the IgE-FcεRI interaction to just one of the two Cε3 domains in IgE-Fc, which together constitute the high affinity binding site, results in 1000-fold reduced affinity. Such attenuation, effected by a small molecule binding to part of the IgE:FcεRI interface or a distant allosteric site, rather than complete blocking of the interaction, may represent a viable approach to the treatment of allergic disease. However, the degree to which the interaction would need to be disrupted is unclear, because the importance of high affinity for immediate hypersensitivity has never been investigated. We have incorporated into human IgE a mutation, R334S, previously characterized in IgE-Fc, which reduces its affinity for FcεRI ∼50-fold. We have compared the ability of wild type and R334S IgE to stimulate allergen-induced mast cell activation in vitro and in vivo. We confirmed the expected difference in affinity between wild type and mutant IgE for FcεRI (∼50-fold) and found that, in vitro, mast cell degranulation was reduced proportionately. The effect in vivo was also marked, with a 75% reduction in the passive cutaneous anaphylaxis response. We have therefore demonstrated that the high affinity of IgE for FcεRI is critical to the allergic response, and that even moderate attenuation of this affinity has a substantial effect in vivo. PMID:18703499

  3. Effect of skin wettedness on sweat gland response

    NASA Technical Reports Server (NTRS)

    Nadel, E. R.; Stolwijk, J. A. J.

    1973-01-01

    Investigation of the effect of skin wettedness upon sweating rate. Several techniques were used to gain a better understanding of the quantitative nature of this effect. The results include the finding that the evaporative power of the environment has a profound effect on the relationship between body temperature and sweating rate.

  4. Comparative analysis of the acute response of zebrafish Danio rerio skin to two different bacterial infections.

    PubMed

    Lü, Aijun; Hu, Xiucai; Wang, Yi; Shen, Xiaojing; Zhu, Aihua; Shen, Lulu; Ming, Qinglei; Feng, Zhaojun

    2013-12-01

    Skin is an important innate immune organ in fish; however, little is known about the skin's immune response to infectious pathogens. We conducted a comparative analysis of the acute immune response of Zebrafish Danio rerio skin against gram-positive (Staphylococcus chromogenes) and gram-negative (Citrobacter freundii) bacterial infections. Gene expression profiles induced from the two different infections were identified by microarray hybridization, with many genes demonstrating an acute immune response in the skin. Differentially expressed genes were mainly involved in response to stress and stimulus, complement activation, acute-phase response, and defense and immune response. Compared with transcription patterns of skin from the two infections, a similar innate immunity (e.g., transferrin, coagulation factor, complements, and lectins) was observed but with different acute-phase genes (e.g., ceruloplasmin, alpha-1-microglobulin, vitellogenin, and heat shock protein). These results suggest that the skin of fish plays an important role in the innate immune responses to bacterial infection. PMID:24341765

  5. Management of Rhinitis: Allergic and Non-Allergic

    PubMed Central

    Tran, Nguyen P; Vickery, John

    2011-01-01

    Rhinitis is a global problem and is defined as the presence of at least one of the following: congestion, rhinorrhea, sneezing, nasal itching, and nasal obstruction. The two major classifications are allergic and nonallergic rhinitis (NAR). Allergic rhinitis occurs when an allergen is the trigger for the nasal symptoms. NAR is when obstruction and rhinorrhea occurs in relation to nonallergic, noninfectious triggers such as change in the weather, exposure to caustic odors or cigarette smoke, barometric pressure differences, etc. There is a lack of concomitant allergic disease, determined by negative skin prick test for relevant allergens and/or negative allergen-specific antibody tests. Both are highly prevalent diseases that have a significant economic burden on society and negative impact on patient quality of life. Treatment of allergic rhinitis includes allergen avoidance, antihistamines (oral and intranasal), intranasal corticosteroids, intranasal cromones, leukotriene receptor antagonists, and immunotherapy. Occasional systemic corticosteroids and decongestants (oral and topical) are also used. NAR has 8 major subtypes which includes nonallergic rhinopathy (previously known as vasomotor rhinitis), nonallergic rhinitis with eosinophilia, atrophic rhinitis, senile rhinitis, gustatory rhinitis, drug-induced rhinitis, hormonal-induced rhinitis, and cerebral spinal fluid leak. The mainstay of treatment for NAR are intranasal corticosteroids. Topical antihistamines have also been found to be efficacious. Topical anticholinergics such as ipratropium bromide (0.03%) nasal spray are effective in treating rhinorrhea symptoms. Adjunct therapy includes decongestants and nasal saline. Investigational therapies in the treatment of NAR discussed include capsaicin, silver nitrate, and acupuncture. PMID:21738880

  6. Differential effects of endogenous and exogenous interferon-gamma on immunoglobulin E, cellular infiltration, and airway responsiveness in a murine model of allergic asthma.

    PubMed

    Hofstra, C L; Van Ark, I; Hofman, G; Nijkamp, F P; Jardieu, P M; Van Oosterhout, A J

    1998-11-01

    The inflammatory response as seen in human allergic asthma is thought to be regulated by Th2 cells. It has been shown that interferon-gamma (IFN-gamma) can downregulate the proliferation of Th2 cells and therefore might be of therapeutic use. In the present study we have investigated the in vivo role of endogenous and exogenous IFN-gamma in a murine model with features reminiscent of human allergic asthma. IFN-gamma gene knockout (GKO) and wild-type mice were sensitized with ovalbumin and exposed to repeated ovalbumin aerosol challenges. In addition, wild-type mice were treated with intraperitoneal or nebulized recombinant murine IFN-gamma during the challenge period. Sensitized wild-type mice exhibited upregulated ovalbumin-specific IgE in serum, and airway hyperresponsiveness and infiltration of eosinophils and mononuclear cells in the bronchoalveolar lavage fluid (BALF) after ovalbumin challenge. In contrast, in GKO mice only reduced eosinophilic infiltration in the BALF was observed after ovalbumin challenge. In wild-type mice, parenteral IFN-gamma treatment downregulated ovalbumin-specific IgE levels in serum, and airway hyperresponsiveness and cellular infiltration in the BALF, whereas aerosolized IFN-gamma treatment only suppressed airway hyperresponsiveness. In vitro experiments showed that these effects of IFN-gamma appear not to be mediated via a direct effect on the cytokine production of antigen-specific Th2 cells. These data indicate that airway hyperresponsiveness can be downregulated by IFN-gamma locally in the airways, whereas for downregulation of IgE and cellular infiltration systemic IFN-gamma is needed. The present study shows that exogenous IFN-gamma can downregulate the allergic response via an antigen-specific T-cell independent mechanism, but at the same time endogenous IFN-gamma plays a role in an optimal response. PMID:9806748

  7. The use of infrared thermography to detect the skin temperature response to physical activity

    NASA Astrophysics Data System (ADS)

    Tanda, G.

    2015-11-01

    Physical activity has a noticeable effect on skin blood flow and temperature. The thermal regulatory and hemodynamic processes during physical activity are controlled by two conflicting mechanisms: the skin vasoconstriction induced by the blood flow demand to active muscles and the skin vasodilation required by thermoregulation to increase warm blood flow and heat conduction to the skin. The time-evolution of skin temperature during exercise can give useful information about the adaptation of the subject as a function of specific type, intensity and duration of exercise. In this paper, infrared thermography is used to investigate the thermal response of skin temperature during running exercise on treadmill for a group of seven healthy and trained runners. Two different treadmill exercises are considered: a graded load exercise and a constant load exercise; for both exercises the duration was 30 minutes. Within the limits due to the relatively small size of the sample group, results typically indicate a fall in skin temperature during the initial stage of running exercise. As the exercise progresses, the dynamics of the skin temperature response depends on the type of exercise (graded versus constant load) and probably on the level of training of the subject.

  8. 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...

  9. Eosinophilic Inflammation in Allergic Asthma

    PubMed Central

    Possa, Samantha S.; Leick, Edna A.; Prado, Carla M.; Martins, Mílton A.; Tibério, Iolanda F. L. C.

    2013-01-01

    Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma. PMID:23616768

  10. Allergic rhinitis - what to ask your doctor - child

    MedlinePlus

    ... How do I find out when smog or pollution is worse in our area? What does my ... More Allergen Allergic rhinitis Allergies - overview Allergy testing - skin Asthma and allergy - resources Common cold Sneezing Patient ...

  11. Allergic rhinitis - what to ask your doctor - adult

    MedlinePlus

    ... How do I find out when smog or pollution is worse in my area? Am I taking ... More Allergen Allergic rhinitis Allergies - overview Allergy testing - skin Asthma and allergy - resources Common cold Sneezing Patient ...

  12. Differences in thermal optical response between intact diabetic and nondiabetic human skin

    NASA Astrophysics Data System (ADS)

    Yeh, Shu-Jen; Hanna, Charles F.; Kantor, Stan; Hohs, Ronald; Khalil, Omar S.

    2003-07-01

    We observed a difference in the thermal response of localized reflectance signal of human skin between type-2 diabetic and non-diabetic volunteers. We investigated the use of this thermo-optical behavior as a basis for a non-invasive method for the determination of the diabetic status of a subject. We used a two-site temperature differential method, which is predicated upon the measurement of localized reflectance from two areas on the surface of the skin, each of these areas is subjected to a different thermal perturbation. The response of skin localized reflectance to temperature was measured and used in a classification algorithm. We used a discriminant function to classify subjects as diabetics or non-diabetics. In a prediction set of 24 non-invasive tests collected from 6 diabetics and 6 non-diabetics, the sensitivity ranged between 73% and 100%, and the specificity ranged between 75% and 100%, depending on the thermal conditions and probe-skin contact time. The difference in thermo-optical response of the skin of the two groups may be explained in terms of difference in response of cutaneous microcirculation to temperature, which is manifested as a difference in the near infrared light absorption and scattering. Another factor is the difference in the temperature response of the scattering coefficient between the two groups, which may be caused by cutaneous structural differences induced by non-enzymatic glycation of skin protein fibers, and/or by the difference in blood cell aggregation.

  13. Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses.

    PubMed

    Morisaki, Naoko; Moriwaki, Shigeru; Sugiyama-Nakagiri, Yoriko; Haketa, Keiichi; Takema, Yoshinori; Imokawa, Genji

    2010-12-17

    Although human skin fibroblast (HSF) elastase has been characterized as a membrane-bound metalloproteinase, little is known about its structure, amino acid sequence, and encoding gene. As there are similarities in the molecular weights and inhibitory profiles of HSF elastase and neprilysin (neutral endopeptidase 24.11 (NEP)), in this study we tested the hypothesis that they are identical using immunoprecipitation and transfection methods. An immunoprecipitation study demonstrated that HSF elastase activity co-immunoprecipitated with anti-NEP in lysates of cultured HSF. Transfection of an NEP cDNA expression vector into COS-1 cells elicited the expression of HSF elastase and NEP activities in the transfected cells. These findings strongly suggest that HSF elastase is identical to NEP, which functions mainly in neuron-associated cells to degrade neuropeptides. Analysis of the expression pattern of NEP revealed that its expression was remarkably up-regulated at the gene, protein, and enzymatic activity levels during the replicative senescence of cultured HSF. Further, the activity of NEP was markedly enhanced in a pattern similar to elastase activity during the intrinsic aging of mouse skin, in UVA-exposed HSF as well as in HSF treated with conditioned medium from UVB-exposed human keratinocytes. Analysis of the cytokine profile for the stimulation of NEP and HSF elastase activities in HSF demonstrated that among the 11 cytokines tested, IL-1α, IL-1β, IL-6, IL-8, and GM-CSF had the potential to significantly stimulate both activities similarly, again supporting the identity of HSF elastase and NEP. PMID:20876573

  14. Inhibitory effect of fermented Arctium lappa fruit extract on the IgE-mediated allergic response in RBL‑2H3 cells.

    PubMed

    Yoo, Jae-Myung; Yang, Ju Hye; Yang, Hye Jin; Cho, Won-Kyung; Ma, Jin Yeul

    2016-02-01

    Arctium lappa fruit has been used in traditional medicine, and it is known to exert beneficial effects, such as antioxidant, anti-inflammatory and anticancer effects. However, the effects of the Arctium lappa fruit on the allergic response remain unknown. In this study, we evaluated the anti-allergic effects of Arctium lappa fruit extract (AFE) and its fermented form (F-AFE) using immunoglobulin E (IgE)-activated RBL‑2H3 cells. To investigate the anti-allergic effects of AFE or F-AFE, we examined the release of β-hexosaminidase, a key biomarker of degranulation during an allergic reaction, and the production of pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) in the cells treated with or without the above-mentioned extracts. AFE weakly inhibited the release of β-hexosaminidase, whereas F-AFE significantly suppressed the release of β-hexosaminidase in a dose-dependent manner. Consistently, F-AFE suppressed the production of TNF-α and PGE2 in a dose-dependent manner. F-AFE exerted an inhibitory effect on the production of β-hexosaminidase, TNF-α and PGE2 with an IC50 value of 30.73, 46.96 and 36.27 µg/ml, respectively. Furthermore, F-AFE inhibited the phosphorylation of Lyn, Fyn and Syk, which are involved in the FcεRI signaling pathway, that of phosphoinositide phospholipase C (PLC)γ1/2 and protein kinase C (PKC)δ, which are associated with the degranulation process, as well as that of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK), p38 and Akt, which are associated with cytokine expression. In the late phase, F-AFE partially suppressed the phosphorylation of cytosolic phospholipase A2 (cPLA2), but not the expression of cyclooxygenase (COX)-2. To compare and identify the major components of the two extracts, we used high-performance liquid chromatography. The levels of arctigenin, one of the major compounds, were elevated 6-fold in F-AFE compared with AFE, whereas the

  15. 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...

  16. Biology of human skin transplanted to the nude mouse: I. Response to agents which modify epidermal proliferation.

    PubMed

    Krueger, G G; Shelby, J

    1981-06-01

    To accept human skin transplanted to the congenitally athymic (nude) mouse as a system to study human skin and its physiologic and pathologic states, it must be demonstrated that skin so maintained retains its function as a biologic unit. We have found that responses of grafted human skin and nude mouse skin to various agents differ. This difference in response has been utilized to assess barrier function and proliferative capacity of human skin grafts. Human skin grafts undergo a proliferative response when 10 ng of the tumor promoter, 12-O-tetradecanoyl phorbol 13-acetate (TPA) is applied. Nudes do not respond to this dose. Increasing the dose to 100 ng of TPA evokes a response in both. However, only in the human skin grafts can this response be blocked with betamethasone valerate (BV). In that human skin grafts do not take on their hosts' responsiveness, and the response of domestic pig skin to these agents before and after grafting is identical, the conclusion is reached that human skin appears to retain its inherent biologic unit function. The data also demonstrate some of the potential of this system to study kinetics of the epidermis of human skin. PMID:7017014

  17. Environmental protection from allergic diseases: From humans to mice and back.

    PubMed

    Schaub, Bianca; Vercelli, Donata

    2015-10-01

    Allergic diseases have a strong environmental component, illustrated by the rapid rise of their prevalence in the Western world. Environmental exposures have been consistently shown to either promote or protect against allergic disease. Here we focus on protective exposures and the pathways they regulate. Traditional farming, natural environments with high biodiversity, and pets in the home (particularly dogs) have the most potent and consistent allergy-protective effects and are actively investigated to identify the environmental and host-based factors that confer allergy protection. Recent work emphasizes the critical protective role of microbial diversity and its interactions with the gut/lung and skin/lung axes-a cross-talk through which microbial exposure in the gut or skin powerfully influences immune responses in the lung. PMID:26210896

  18. Laboratory annoyance and skin conductance responses to some natural sounds

    NASA Astrophysics Data System (ADS)

    Björk, E. A.

    1986-09-01

    The influences of spectral properties of sounds on annoyance and electrodermal activity reactions have been studied. In two laboratory experiments, subjects were exposed to some natural sounds in semi-anechoic conditions. Skin conductance and annoyance reactions were determined. The results suggest that electrodermal activity increases when the A-weighted equivalent sound pressure level exceeds 70 dB(A). It is concluded that the width of the spectrum is relevant, and that the greater the fundamental frequency of the harmonic spectrum the more annoying the sound.

  19. [Infectious-allergic bronchopulmonary paecilomycosis].

    PubMed

    Akhunova, A M

    1991-01-01

    Primary or secondary infection of the lungs with fungi of the Paecilomyces family (P. variotii and P. viridis) gives rise to the development of infectious allergic bronchopulmonary paecilomycosis characterized by the presence of chronic allergic interstitial pneumonia and obstructive bronchitis, bronchial asthma, total and pulmonary eosinophilia, the presence of the tissue parasitic form of the fungus in sputum, blood, pulmonary tissue, the presence of allergen-specific IgE and/or IgG antibodies in patients' sera, immediate or double (20 min and 6 h) reaction of the skin to administration of allergen of Paecilomyces, by not infrequent combination of lung damage and impairment of other organs as well as by chronic relapses. PMID:1805416

  20. 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

  1. Therapeutic strategies for allergic diseases

    NASA Astrophysics Data System (ADS)

    Barnes, Peter J.

    1999-11-01

    Many drugs are now in development for the treatment of atopic diseases, including asthma, allergic rhinitis and atopic dermatitis. These treatments are based on improvements in existing therapies or on a better understanding of the cellular and molecular mechanisms involved in atopic diseases. Although most attention has been focused on asthma, treatments that inhibit the atopic disease process would have application to all atopic diseases, as they often coincide. Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments.

  2. Effects of Olopatadine Hydrochloride, a Histamine H1 Receptor Antagonist, on Histamine-Induced Skin Responses

    PubMed Central

    Hashimoto, Takashi; Ishii, Norito; Hamada, Takahiro; Dainichi, Teruki; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H1 receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration. PMID:20886023

  3. Skin Conductance Responses to Another Person's Gaze in Children with Autism

    ERIC Educational Resources Information Center

    Kylliainen, Anneli; Hietanen, Jari K.

    2006-01-01

    The effects of another person's gaze on physiological arousal were investigated by measuring skin conductance responses (SCR). Twelve able children with autism and 12 control children were shown face stimuli with straight gaze (eye contact) or averted gaze on a computer monitor. In children with autism, the responses to straight gaze were stronger…

  4. Stuttered and Fluent Speakers' Heart Rate and Skin Conductance in Response to Fluent and Stuttered Speech

    ERIC Educational Resources Information Center

    Zhang, Jianliang; Kalinowski, Joseph; Saltuklaroglu, Tim; Hudock, Daniel

    2010-01-01

    Background: Previous studies have found simultaneous increases in skin conductance response and decreases in heart rate when normally fluent speakers watched and listened to stuttered speech compared with fluent speech, suggesting that stuttering induces arousal and emotional unpleasantness in listeners. However, physiological responses of persons…

  5. A suction blister model reliably assesses skin barrier restoration and immune response.

    PubMed

    Smith, Tracey J; Wilson, Marques A; Young, Andrew J; Montain, Scott J

    2015-02-01

    Skin wound healing models can be used to detect changes in immune function in response to interventions. This study used a test-retest format to assess the reliability of a skin suction blister procedure for quantitatively evaluating human immune function in repeated measures type studies. Up to eight suction blisters (~30 mm(2)) were induced via suction on each participant's left and right forearm (randomized order; blister session 1 and 2), separated by approximately one week. Fluid was sampled from each blister, and the top layer of each blister was removed to reveal up to eight skin wounds. Fluid from each wound was collected 4, 7 and 24h after blisters were induced, and proinflammatory cytokines were measured. Transepidermal water loss (TEWL), to assess skin barrier recovery, was measured daily at each wound site until values were within 90% of baseline values (i.e., unbroken skin). Sleep, stress and inflammation (i.e., factors that affect wound healing and immune function), preceding the blister induction, were assessed via activity monitors (Actical, Philips Respironics, Murrysville, Pennsylvania), the Perceived Stress Scale (PSS) and C-reactive protein (CRP), respectively. Area-under-the-curve and TEWL, between blister session 1 and 2, were compared using Pearson correlations and partial correlations (controlling for average nightly sleep, PSS scores and CRP). The suction blister method was considered reliable for assessing immune response and skin barrier recovery if correlation coefficients reached 0.7. Volunteers (n=16; 12 M; 4F) were 23 ± 5 years [mean ± SD]. Time to skin barrier restoration was 4.9 ± 0.8 and 4.8 ± 0.9 days for sessions 1 and 2, respectively. Correlation coefficients for skin barrier restoration, IL-6, IL-8 and MIP-1α were 0.9 (P<0.0001), 0.7 (P=0.008) and 0.9 (P<0.0001), respectively. When average nightly sleep, PSS scores and CRP (i.e., percent difference between sessions 1 and 2) were taken into consideration, correlations in

  6. Role of Predatory Mites in Persistent Nonoccupational Allergic Rhinitis

    PubMed Central

    Poza Guedes, Paloma; Sánchez Machín, Inmaculada; Matheu, Víctor; Iraola, Víctor

    2016-01-01

    Mites can sensitize and induce atopic disease in predisposed individuals and are an important deteriorating factor in patients with allergic rhinitis, asthma, and atopic dermatitis. Although Pyroglyphidae mites have been extensively studied, very scarce reports are available on Cheyletidae spp. especially regarding human respiratory pathology. The main objective of the present study is to investigate the clinical role of this predator mite (Cheyletus eruditus) as a respiratory antigen in a selected sensitized human population. Fifty-two adult patients were recruited from the outpatient allergy clinic to assess their eligibility for the study. The thirty-seven subjects with persistent allergic rhinitis (PAR) who fulfilled the ARIA criteria had a positive IgE response confirmed by skin prick test (SPT) to C. eruditus. Only those individuals (37/47) with a positive SPT to C. eruditus showed a positive nasal provocation test (NPT), while 10 patients with nonallergic mild-to-moderate persistent rhinitis, control group, had a negative NPT with C. eruditus. The present paper describes a new role for the predator mite Cheyletus eruditus as a respiratory allergen in a selected subset of patients in a subtropical environment afflicted with persistent nonoccupational allergic rhinitis. PMID:27445552

  7. Environmental Changes, Microbiota, and Allergic Diseases

    PubMed Central

    Kim, Byoung-Ju; Lee, So-Yeon; Kim, Hyo-Bin; Lee, Eun

    2014-01-01

    During the last few decades, the prevalence of allergic disease has increased dramatically. The development of allergic diseases has been attributed to complex interactions between environmental factors and genetic factors. Of the many possible environmental factors, most research has focused on the most commonly encountered environmental factors, such as air pollution and environmental microbiota in combination with climate change. There is increasing evidence that such environmental factors play a critical role in the regulation of the immune response that is associated with allergic diseases, especially in genetically susceptible individuals. This review deals with not only these environmental factors and genetic factors but also their interactions in the development of allergic diseases. It will also emphasize the need for early interventions that can prevent the development of allergic diseases in susceptible populations and how these interventions can be identified. PMID:25228995

  8. Immune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

    PubMed Central

    2011-01-01

    Background Methylene diphenyl diisocyanate (MDI), a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Methods Mice exposed via the skin to varying doses (0.1-10% w/v) of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA), while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL). Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Results Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary) respiratory tract inflammation and eosinophilia depended upon the (primary) skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI). The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. Conclusions MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma pathogenesis. MDI

  9. Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells

    PubMed Central

    Akdis, Mübeccel; Verhagen, Johan; Taylor, Alison; Karamloo, Fariba; Karagiannidis, Christian; Crameri, Reto; Thunberg, Sarah; Deniz, Günnur; Valenta, Rudolf; Fiebig, Helmut; Kegel, Christian; Disch, Rainer; Schmidt-Weber, Carsten B.; Blaser, Kurt; Akdis, Cezmi A.

    2004-01-01

    The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy. PMID:15173208

  10. Cassia tora Seed Extract and Its Active Compound Aurantio-obtusin Inhibit Allergic Responses in IgE-Mediated Mast Cells and Anaphylactic Models.

    PubMed

    Kim, Myungsuk; Lim, Sue Ji; Lee, Hee-Ju; Nho, Chu Won

    2015-10-21

    Cassia tora seed is widely used due to its various biological properties including anticancer, antidiabetic, and anti-inflammatory effects. However, there has been no report of the effects of C. tora seed extract (CTE) on immunoglobulin E (IgE)-mediated allergic responses. In this research, we demonstrated the effects of CTE and its active compound aurantio-obtusin on IgE-sensitized allergic reactions in mast cells and passive cutaneous anaphylaxis (PCA). CTE and aurantio-obtusin suppressed degranulation, histamine production, and reactive oxygen species generation and inhibited the production and mRNA expression of tumor necrosis factor-α and interleukin-4. CTE and aurantio-obtusin also suppressed the prostaglandin E2 production and expression of cyclooxygenase 2. Furthermore, CTE and aurantio-obtusin suppressed IgE-mediated FcεRI signaling such as phosphorylation of Syk, protein kinase Cμ, phospholipase Cγ, and extracellular signal-regulated kinases. CTE and aurantio-obtusin blocked mast cell-dependent PCA in IgE-mediated mice. These results suggest that CTE and aurantio-obtusin are a beneficial treatment for allergy-related diseases. PMID:26434611

  11. Diminished lymphocyte adhesion and alleviation of allergic responses by small-molecule- or antibody-mediated inhibition of L-selectin functions.

    PubMed

    Oostingh, Gertie J; Ludwig, Ralf J; Enders, Sven; Grüner, Sabine; Harms, Gesche; Boehncke, W Henning; Nieswandt, Bernhard; Tauber, Rudolf; Schön, Michael P

    2007-01-01

    Selectins are attractive targets for specific anti-inflammatory therapies. Using human lymphocytes as well as an L-selectin-transfected pre-B-cell line in dynamic flow chamber experiments, we could demonstrate that the small-molecule compound efomycine M blocks L-selectin-mediated lymphocyte rolling on sialylated Lewis(X), an action that was confirmed by plasmon resonance spectroscopy. Recruitment of naive lymphocytes to peripheral lymph nodes depends on L-selectin-mediated adhesion to high endothelial venules. We performed intravital microscopy studying lymphocyte rolling in peripheral lymph nodes and showed a 53% reduction (P=0.0006) of lymphocyte rolling in mice treated with efomycine M or a function-blocking antibody against L-selectin. In addition, the number of lymph node-homing T cells was reduced by >60% using either efomycine M or L-selectin-blocking antibodies. As recruitment of naive lymphocytes is a prerequisite for sensitization in T-cell-mediated immune reactions and allergic responses, mice were treated with efomycine M or an L-selectin-specific antibody during contact sensitization with DNFB. After adoptive transfer of corresponding T cells into non-sensitized recipient mice, the capacity of these cells to induce contact hypersensitivity was significantly reduced (P=0.0002 and P=0.0001, respectively). Our data demonstrate that it is possible, in principle, to diminish T-cell-mediated allergic reactions through interference with L-selectin functions during the early sensitization phase. PMID:16902419

  12. The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis

    PubMed Central

    Son, Hye Ran; Rhee, Yun-Hee; Kim, Eun Hee; Kim, Ji Hye; Bae, Jun-Sang; Chung, Young-Jun; Chung, Phil-Sang; Raz, Eyal; Mo, Ji-Hun

    2016-01-01

    Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR. PMID:26700618

  13. Pneumococcal components induce regulatory T cells that attenuate the development of allergic airways disease by deviating and suppressing the immune response to allergen.

    PubMed

    Thorburn, Alison N; Brown, Alexandra C; Nair, Prema M; Chevalier, Nina; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M

    2013-10-15

    The induction of regulatory T cells (Tregs) to suppress aberrant inflammation and immunity has potential as a therapeutic strategy for asthma. Recently, we identified key immunoregulatory components of Streptococcus pneumoniae, type 3 polysaccharide and pneumolysoid (T+P), which suppress allergic airways disease (AAD) in mouse models of asthma. To elucidate the mechanisms of suppression, we have now performed a thorough examination of the role of Tregs. BALB/c mice were sensitized to OVA (day 0) i.p. and challenged intranasal (12-15 d later) to induce AAD. T+P was administered intratracheally at the time of sensitization in three doses (0, 12, and 24 h). T+P treatment induced an early (36 h-4 d) expansion of Tregs in the mediastinal lymph nodes, and later (12-16 d) increases in these cells in the lungs, compared with untreated allergic controls. Anti-CD25 treatment showed that Treg-priming events involving CD25, CCR7, IL-2, and TGF-β were required for the suppression of AAD. During AAD, T+P-induced Tregs in the lungs displayed a highly suppressive phenotype and had an increased functional capacity. T+P also blocked the induction of IL-6 to prevent the Th17 response, attenuated the expression of the costimulatory molecule CD86 on myeloid dendritic cells (DCs), and reduced the number of DCs carrying OVA in the lung and mediastinal lymph nodes. Therefore, bacterial components (T+P) drive the differentiation of highly suppressive Tregs, which suppress the Th2 response, prevent the Th17 response and disable the DC response resulting in the effective suppression of AAD. PMID:24048894

  14. Homeostatic Tissue Responses in Skin Biopsies from NOMID Patients with Constitutive Overproduction of IL-1β

    PubMed Central

    Aubert, Pamela; Suárez-Fariñas, Mayte; Mitsui, Hiroshi; Johnson-Huang, Leanne M.; Harden, Jamie Lynn; Pierson, Katherine C.; Dolan, Joseph G.; Novitskaya, Inna; Coats, Israel; Estes, Jacob; Cowen, Edward W.; Plass, Nicole; Lee, Chyi-Chia Richard; Sun, Hong-Wei

    2012-01-01

    The autoinflammatory disorder, Neonatal-onset Multisystem Inflammatory Disease (NOMID) is the most severe phenotype of disorders caused by mutations in CIAS1 that result in increased production and secretion of active IL-1β. NOMID patients present with systemic and organ-specific inflammation of the skin, central nervous system and bone, and respond dramatically to treatment with IL-1 blocking agents. We compared the cellular infiltrates and transcriptome of skin biopsies from patients with NOMID (n = 14) before treatment (lesional (LS) and non-lesional (pre-NL) skin) and after treatment (post-NL) with the IL-1 blocker anakinra (recombinant IL-1 receptor antagonist, Kineret®, Swedish Orphan Biovitrum AB, SOBI), to normal skin (n = 5) to assess tissue responses in the context of untreated and treated disease. Abundant neutrophils distinguish LS skin from pre-NL and post-NL skin. CD11c+ dermal dendritic cells and CD163+ macrophages expressed activated caspase-1 and are a likely source of cutaneous IL-1 production. Treatment with anakinra led to the disappearance of neutrophils, but CD3+ T cells and HLA-DR+ cells remained elevated. Among the upregulated genes IL-6, IL-8, TNF, IL-17A, CCL20, and the neutrophil defensins DEFA1 and DEFA3 were differentially regulated in LS tissues (compared to normal skin). Important significantly downregulated pathways in LS skin included IL-1R/TLR signaling, type I and II cytokine receptor signaling, mitochondrial dysfunction, and antigen presentation. The differential expression and regulation of microRNAs and pathways involved in post-transcriptional modification were suggestive of epigenetic modification in the chronically inflamed tissue. Overall, the dysregulated genes and pathways suggest extensive “adaptive” mechanisms to control inflammation and maintain tissue homeostasis, likely triggered by chronic IL-1 release in the skin of patients with NOMID. PMID:23226210

  15. A dual role for complement in allergic asthma.

    PubMed

    Köhl, Jörg; Wills-Karp, Marsha

    2007-06-01

    Complement is an ancient danger-sensor system of innate immunity, providing first-line defence against pathogens. Concordant with its pro-inflammatory properties, complement contributes to airway inflammation, hyperresponsiveness and mucus production during the effector phase of allergic asthma. In contrast to these pro-allergic properties, complement can also protect from the development of the maladaptive Th2-biased immune response that drives airway inflammation and hyperreactivity in allergic asthma. As such, selective targeting of pro-allergic complement pathways appears an attractive therapeutic option in allergic asthma. PMID:17475559

  16. Sympathetic Responses to Noxious Stimulation of Muscle and Skin

    PubMed Central

    Burton, Alexander R.; Fazalbhoy, Azharuddin; Macefield, Vaughan G.

    2016-01-01

    Acute pain triggers adaptive physiological responses that serve as protective mechanisms that prevent continuing damage to tissues and cause the individual to react to remove or escape the painful stimulus. However, an extension of the pain response beyond signaling tissue damage and healing, such as in chronic pain states, serves no particular biological function; it is maladaptive. The increasing number of chronic pain sufferers is concerning, and the associated disease burden is putting healthcare systems around the world under significant pressure. The incapacitating effects of long-lasting pain are not just psychological – reflexes driven by nociceptors during the establishment of chronic pain may cause serious physiological consequences on regulation of other body systems. The sympathetic nervous system is inherently involved in a host of physiological responses evoked by noxious stimulation. Experimental animal and human models demonstrate a diverse array of heterogeneous reactions to nociception. The purpose of this review is to understand how pain affects the sympathetic nervous system by investigating the reflex cardiovascular and neural responses to acute pain and the long-lasting physiological responses to prolonged (tonic) pain. By observing the sympathetic responses to long-lasting pain, we can begin to understand the physiological consequences of long-term pain on cardiovascular regulation. PMID:27445972

  17. Sympathetic Responses to Noxious Stimulation of Muscle and Skin.

    PubMed

    Burton, Alexander R; Fazalbhoy, Azharuddin; Macefield, Vaughan G

    2016-01-01

    Acute pain triggers adaptive physiological responses that serve as protective mechanisms that prevent continuing damage to tissues and cause the individual to react to remove or escape the painful stimulus. However, an extension of the pain response beyond signaling tissue damage and healing, such as in chronic pain states, serves no particular biological function; it is maladaptive. The increasing number of chronic pain sufferers is concerning, and the associated disease burden is putting healthcare systems around the world under significant pressure. The incapacitating effects of long-lasting pain are not just psychological - reflexes driven by nociceptors during the establishment of chronic pain may cause serious physiological consequences on regulation of other body systems. The sympathetic nervous system is inherently involved in a host of physiological responses evoked by noxious stimulation. Experimental animal and human models demonstrate a diverse array of heterogeneous reactions to nociception. The purpose of this review is to understand how pain affects the sympathetic nervous system by investigating the reflex cardiovascular and neural responses to acute pain and the long-lasting physiological responses to prolonged (tonic) pain. By observing the sympathetic responses to long-lasting pain, we can begin to understand the physiological consequences of long-term pain on cardiovascular regulation. PMID:27445972

  18. Acute stress affects the physiology and behavior of allergic mice.

    PubMed

    Sutherland, M A; Shome, G P; Hulbert, L E; Krebs, N; Wachtel, M; McGlone, J J

    2009-09-01

    Physical and psychological stressors have been implicated in acute asthma exacerbation. The objective of the current study was to determine the effects of forced swimming stress (FST) on allergic pulmonary inflammation in BALB/c mice. Eighty female mice were allocated to one of four treatments arranged in a 2 x 2 factorial consisting of two levels of allergy and two levels of stress. The effects of stress and allergy were assessed by examination of cytokines and leukocyte differentials in the bronchoalveolar lavage fluid, corticosterone and immunoglobulin (Ig) E in the plasma, leukocyte differentials in the peripheral blood, natural killer cytotoxicity, and histopathology of the lungs. Behavior was recorded during the FST. Stress and allergy increased plasma corticosterone in mice. Allergy increased IgE concentrations and pulmonary inflammation. Interleukin-4 was greater among allergic stressed and non-stressed mice and stressed, non-allergic mice compared with non-stressed, non-allergic mice. Interleukin-5 (IL-5) and 6 (IL-6) were greater among allergic stressed and non-stressed mice compared with non-allergic mice. Interleukin-5 and 6 were reduced among stressed-allergic mice compared with non-stressed, allergic mice. Stress and allergy shifted mice towards a T-helper 2 response as shown by increased interleukin-4. Stress reduced IL-5 and IL-6 in allergic mice but not non-allergic mice. Pulmonary inflammation was not reduced among allergic stressed mice in spite of elevated glucocorticoids. Mice induced to be allergic responded to FST differently than non-allergic mice. Our findings suggest that stress induces a differential response among allergic and non-allergic mice. PMID:19527741

  19. Extracellular superoxide dismutase ameliorates house dust mite-induced atopic dermatitis-like skin inflammation and inhibits mast cell activation in mice.

    PubMed

    Lee, Yun Sang; Choi, Jung-Hye; Lee, Ji-Hyun; Lee, Han-Woong; Lee, Weontae; Kim, Woo Taek; Kim, Tae-Yoon

    2016-08-01

    Extracellular superoxide dismutase (EC-SOD) is an enzyme that catalyses the dismutation of superoxide anions. It has multiple functions, such as reactive oxygen species scavenging, anti-angiogenic, anti-inflammatory, antichemotatic and antitumor activities. Recently, we demonstrated that EC-SOD inhibits ovalbumin-induced allergic airway inflammation in mice. However, the anti-allergic effect of EC-SOD on skin tissue and the role of EC-SOD in mast cells, which are important for allergic responses, have not been well studied. In this study, we investigated whether EC-SOD can alleviate atopic dermatitis in mice and inhibit mast cell activation. Treatment with human recombinant EC-SOD ameliorated house dust mite-induced atopic dermatitis in mice. Furthermore, the levels of pro-allergic cytokine gene expression and histamine release increased in EC-SOD KO mast cells and decreased in EC-SOD overexpressing mast cells, suggesting that EC-SOD inhibits mast cell activation. Consistently, a passive cutaneous anaphylaxis experiment showed more blood leakage from EC-SOD KO mouse ear skin, implying that the lack of EC-SOD increases allergic responses. These results suggest that EC-SOD inhibits mast cell activation and atopic dermatitis and that the loss of EC-SOD causes more severe allergic responses, implying that EC-SOD might be a good drug candidate for treatment of allergic disorders, such as atopic dermatitis. PMID:27061078

  20. Short-term cadmium exposure induces stress responses in frog (Pelophylax bergeri) skin organ culture.

    PubMed

    Simoncelli, Francesca; Belia, Silvia; Di Rosa, Ines; Paracucchi, Romina; Rossi, Roberta; La Porta, Gianandrea; Lucentini, Livia; Fagotti, Anna

    2015-12-01

    There have been a few studies on the negative effects of pollutants on amphibian skin, the first structural barrier that interacts with the environment and its potential contaminants. In this study an ex vivo skin organ culture from the amphibian Pelophylax bergeri was used to evaluate cell stress responses induced by short-term exposure to cadmium (Cd), a toxic heavy metal known to be an environmental hazard to both humans and wildlife. Histopathological studies were carried out on skin explants using light microscopy and changes in the expression of stress proteins, such as Metallothionein (MT) and Heat shock proteins (HSPs), were investigated by Real-time RT-PCR. Results revealed that amphibian skin reacts to Cd-induced stress by activating biological responses such as morphological alterations and dose- and time-dependent induction of Mt and Hsp70 mRNA expression, suggesting their potential role as biomarkers of exposure to Cd. This work provides a basis for a better understanding of the tissue-specific responses of amphibian skin as a target organ to Cd exposure and its in vitro use for testing potentially harmful substances present in the environment. PMID:26277541

  1. Effects of Niacin Restriction on Sirtuin and PARP Responses to Photodamage in Human Skin

    PubMed Central

    Benavente, Claudia A.; Schnell, Stephanie A.; Jacobson, Elaine L.

    2012-01-01

    Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), NAD+-dependent enzymes, link cellular energy status with responses to environmental stresses. Skin is frequently exposed to the DNA damaging effects of UV irradiation, a known etiology in skin cancer. Thus, understanding the defense mechanisms in response to UV, including the role of SIRTs and PARPs, may be important in developing skin cancer prevention strategies. Here, we report expression of the seven SIRT family members in human skin. SIRTs gene expressions are progressively upregulated in A431 epidermoid carcinoma cells (SIRTs1 and 3), actinic keratoses (SIRTs 2, 3, 5, 6, and 7) and squamous cell carcinoma (SIRTs 1–7). Photodamage induces dynamic changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occur early after photodamage followed by accumulation later, especially for SIRT4. Niacin restriction, which decreases NAD+, the sirtuin substrate, results in an increase in acetylated proteins, upregulation of SIRTs 2 and 4, increased inherent DNA damage, alterations in SIRT responses to photodamage, abrogation of PARP activation following photodamage, and increased sensitivity to photodamage that is completely reversed by repleting niacin. These data support the hypothesis that SIRTs and PARPs play important roles in resistance to photodamage and identify specific SIRTs that respond to photodamage and may be targets for skin cancer prevention. PMID:22860104

  2. Responses in acral and non-acral skin vasomotion and temperature during lowering of ambient temperature.

    PubMed

    Elstad, Maja; Vanggaard, Leif; Lossius, Astrid H; Walløe, Lars; Bergersen, Tone Kristin

    2014-10-01

    Arteriovenous anastomoses (AVA) in acral skin (palms and soles) have a huge capacity to shunt blood directly from the arteries to the superficial venous plexus of the extremities. We hypothesized that acral skin, which supplies blood to the superficial venous plexus, has a stronger influence on blood flow adjustments during cooling in thermoneutral subjects than does non-acral skin. Thirteen healthy subjects were exposed to stepwise cooling from 32 °C to 25 °C and 17 °C in a climate chamber. Laser Doppler flux and skin temperature were measured simultaneously from the left and right third finger pulp and bilateral upper arm skin. Coherence and correlation analyses were performed of short-term fluctuations at each temperature interval. The flux from finger pulps showed the synchronous spontaneous fluctuations characteristic of skin areas containing AVAs. Fluctuation frequency, amplitude and synchronicity were all higher at 25 °C than at 32 °C and 17 °C (p<0.02). Bilateral flux from the upper arm skin showed an irregular, asynchronous vasomotor pattern with small amplitudes which were independent of ambient temperature. At 32 °C, ipsilateral median flux values from the right arm (95% confidence intervals) were 492 arbitrary units (au) (417, 537) in finger pulp and 43 au (35, 60) in upper arm skin. Flux values gradually decreased in finger pulp to 246 au (109, 363) at 25 °C, before an abrupt fall occurred at a median room temperature of 24 °C, resulting in a flux value of 79 au (31, 116) at 17 °C. In the upper arm skin a gradual fall throughout the cooling period to 21 au (13, 27) at 17 °C was observed. The fact that the response of blood flow to ambient cooling is stronger in acral skin than in non-acral skin suggests that AVAs have a greater capacity to adjust blood flow in thermoneutral zone than arterioles in non-acral skin. PMID:25436967

  3. The Skin That We Sing: Culturally Responsive Choral Music Education

    ERIC Educational Resources Information Center

    Shaw, Julia

    2012-01-01

    This article describes ways that music education can be made more culturally responsive, or congruent with the orientations of culturally diverse students. Music education in the United States has historically been based on Eurocentric frameworks that may no longer be applicable in an increasingly multicultural society. For the many teachers…

  4. Frequency-response-based analysis of respiratory sensor measuring capacitance built across skin

    NASA Astrophysics Data System (ADS)

    Terasawa, Makie; Kumagai, Shinya; Sasaki, Minoru

    2016-04-01

    A capacitive respiratory sensor is studied by attaching the electrodes to the skin. The signal characteristics related to the electrode position and body motion are examined. The frequency response indicates the nearly pure capacitance characteristics. The sensing mechanism model based on the equivalent skin thickness change generated by the body volume change accompanying respiration is reasonably consistent with the experimental results. The sensing method is examined by measuring the frequency response under some different conditions including the grounding issue. The electrode attached to the concave site tends to show a smaller signal difference between inhalation and exhalation. The convex site stabilizes the measurement. The bellyband combined with the electrode realizes stable sensing with comfortable fit on the skin.

  5. Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice

    PubMed Central

    Koegel, Heidi; von Tobel, Lukas; Schäfer, Matthias; Alberti, Siegfried; Kremmer, Elisabeth; Mauch, Cornelia; Hohl, Daniel; Wang, Xiao-Jing; Beer, Hans-Dietmar; Bloch, Wilhelm; Nordheim, Alfred; Werner, Sabine

    2009-01-01

    The transcription factor serum response factor (SRF) plays a crucial role in the development of several organs. However, its role in the skin has not been explored. Here, we show that keratinocytes in normal human and mouse skin expressed high levels of SRF but that SRF expression was strongly downregulated in the hyperproliferative epidermis of wounded and psoriatic skin. Keratinocyte-specific deletion within the mouse SRF locus during embryonic development caused edema and skin blistering, and all animals died in utero. Postnatal loss of mouse SRF in keratinocytes resulted in the development of psoriasis-like skin lesions. These lesions were characterized by inflammation, hyperproliferation, and abnormal differentiation of keratinocytes as well as by disruption of the actin cytoskeleton. Ultrastructural analysis revealed markedly reduced cell-cell and cell-matrix contacts and loss of cell compaction in all epidermal layers. siRNA-mediated knockdown of SRF in primary human keratinocytes revealed that the cytoskeletal abnormalities and adhesion defects were a direct consequence of the loss of SRF. In contrast, the hyperproliferation observed in vivo was an indirect effect that was most likely a consequence of the inflammation. These results reveal that loss of SRF disrupts epidermal homeostasis and strongly suggest its involvement in the pathogenesis of hyperproliferative skin diseases, including psoriasis. PMID:19307725

  6. Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior

    PubMed Central

    Levoe, S. Nikki; Flannery, Brenna M.; Brignolo, Laurie; Imai, Denise M.; Koehne, Amanda; Austin, Adam T.; Bruun, Donald A.; Tancredi, Daniel J.; Lein, Pamela J.

    2015-01-01

    Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory. PMID:25705100

  7. Stress and immune responses in skin of turbot (Scophthalmus maximus) under different stocking densities.

    PubMed

    Jia, Rui; Liu, Bao-Liang; Feng, Wen-Rong; Han, Cen; Huang, Bin; Lei, Ji-Lin

    2016-08-01

    Fish skin and its mucus provide the first line of defense against chemical, physical and biological stressors, but little is known about the role of skin and its mucus in immune response to crowding stress. In the present study, we investigated the stress and immune responses in skin of turbot (Scophthalmus maximus) under different stocking densities. Turbot (average weight 185.4 g) were reared for 120 days under three densities: low density (LD), medium density (MD), and high density (HD). After 120 days, fish were weighed and sampled to obtain blood, mucus and skin tissues which were used for analyses of biochemical parameters and genes expression. The results showed HD treatment significantly suppressed growth and enhanced plasma cortisol and glucose levels (P < 0.05). In mucus, the activities of lysozyme (LZM), alkaline phosphatase (ALP) and esterase in HD treatment were lower than LD and MD treatments (P < 0.05) In skin, HD treatment resulted in up-regulation in malondialdehyde (MDA) formation and heat shock protein 70 (HSP 70) mRNA level, and down-regulation in activity of superoxide dismutase (SOD) and the transcriptions of glutathione-s-transferase (GST), interleukin-1β (IL-1β), tumor necrosis factor -α (TNF-α), insulin-like growth factor- (IGF-) and LZM (P < 0.05). Overall, the data suggested that overly high stocking density was a stressor which caused an immunosuppression in skin of turbot. Moreover, this information would help to understand the skin immunity and their relation with stress and disease in fish. PMID:27235366

  8. Transplantation of Tail Skin to Study Allogeneic CD4 T Cell Responses in Mice

    PubMed Central

    Rossi, Simona W.

    2014-01-01

    The study of T cell responses and their consequences during allo-antigen recognition requires a model that enables one to distinguish between donor and host T cells, to easily monitor the graft, and to adapt the system in order to answer different immunological questions. Medawar and colleagues established allogeneic tail-skin transplantation in mice in 1955. Since then, the skin transplantation model has been continuously modified and adapted to answer specific questions. The use of tail-skin renders this model easy to score for graft rejection, requires neither extensive preparation nor deep anesthesia, is applicable to animals of all genetic background, discourages ischemic necrosis, and permits chemical and biological intervention. In general, both CD4+ and CD8+ allogeneic T cells are responsible for the rejection of allografts since they recognize mismatched major histocompatibility antigens from different mouse strains. Several models have been described for activating allogeneic T cells in skin-transplanted mice. The identification of major histocompatibility complex (MHC) class I and II molecules in different mouse strains including C57BL/6 mice was an important step toward understanding and studying T cell-mediated alloresponses. In the tail-skin transplantation model described here, a three-point mutation (I-Abm12) in the antigen-presenting groove of the MHC-class II (I-Ab) molecule is sufficient to induce strong allogeneic CD4+ T cell activation in C57BL/6 mice. Skin grafts from I-Abm12 mice on C57BL/6 mice are rejected within 12-15 days, while syngeneic grafts are accepted for up to 100 days. The absence of T cells (CD3-/- and Rag2-/- mice) allows skin graft acceptance up to 100 days, which can be overcome by transferring 2 x 104 wild type or transgenic T cells. Adoptively transferred T cells proliferate and produce IFN-γ in I-Abm12-transplanted Rag2-/- mice. PMID:25147005

  9. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma.

    PubMed

    Nemeth, Krisztian; Keane-Myers, Andrea; Brown, Jared M; Metcalfe, Dean D; Gorham, James D; Gorham, Jared D; Bundoc, Virgilio G; Bundoc, Victor G; Hodges, Marcus G; Jelinek, Ivett; Madala, Satish; Karpati, Sarolta; Mezey, Eva

    2010-03-23

    Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-beta production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions--specifically therapy resistant asthma--might also be a likely target of the recently discovered cellular therapy approach using BMSCs. PMID:20231466

  10. Thermal Response of In Vivo Human Skin to Fractional Radiofrequency Microneedle Device

    PubMed Central

    Manuskiatti, Woraphong; Pattanaprichakul, Penvadee; Inthasotti, Siriluk; Sitthinamsuwan, Panitta; Hanamornroongruang, Suchanan; Wanitphakdeedecha, Rungsima; Chu-ongsakol, Sorawuth

    2016-01-01

    Background. Fractional radiofrequency microneedle system (FRMS) is a novel fractional skin resurfacing system. Data on thermal response to this fractional resurfacing technique is limited. Objectives. To investigate histologic response of in vivo human skin to varying energy settings and pulse stacking of a FRMS in dark-skinned subjects. Methods. Two female volunteers who were scheduled for abdominoplasty received treatment with a FRMS with varying energy settings at 6 time periods including 3 months, 1 month, 1 week, 3 days, 1 day, and the time immediately before abdominoplasty. Biopsy specimens were analyzed using hematoxylin and eosin (H&E), Verhoeff-Van Gieson (VVG), colloidal iron, and Fontana-Masson stain. Immunohistochemical study was performed by using Heat Shock Protein 70 (HSP70) antibody and collagen III monoclonal antibody. Results. The average depth of radiofrequency thermal zone (RFTZ) ranged from 100 to 300 μm, correlating with energy levels. Columns of cell necrosis and collagen denaturation followed by inflammatory response were initially demonstrated, with subsequent increasing of mucin at 1 and 3 months after treatment. Immunohistochemical study showed positive stain with HSP70. Conclusion. A single treatment with a FRMS using appropriate energy setting induces neocollagenesis. This wound healing response may serve as a mean to improve the appearance of photodamaged skin and atrophic scars. PMID:27247943

  11. Media Research with a Galvanic Skin Response Biosensor: Some Kids Work Up a Sweat!

    ERIC Educational Resources Information Center

    Clariana, Roy B.

    This study considers the galvanic skin response (GSR) of sixth-grade students (n=20) using print, video, and microcomputer segments. Subjects received all three media treatments, in randomized order. Data for analysis consisted of standardized test scores and GSR measures; a moderate positive relationship was shown between cumulative GSR and…

  12. Activation of Molecular Signatures for Antimicrobial and Innate Defense Responses in Skin with Transglutaminase 1 Deficiency

    PubMed Central

    Uchiyama, Ryosuke; Jitsukawa, Orie; Yamanishi, Kiyofumi

    2016-01-01

    Mutations of the transglutaminase 1 gene (TGM1) are a major cause of autosomal recessive congenital ichthyoses (ARCIs) that are associated with defects in skin barrier structure and function. However, the molecular processes induced by the transglutaminase 1 deficiency are not fully understood. The aim of the present study was to uncover those processes by analysis of cutaneous molecular signatures. Gene expression profiles of wild-type and Tgm1–/–epidermis were assessed using microarrays. Gene ontology analysis of the data showed that genes for innate defense responses were up-regulated in Tgm1–/–epidermis. Based on that result, the induction of Il1b and antimicrobial peptide genes, S100a8, S100a9, Defb14, Camp, Slpi, Lcn2, Ccl20 and Wfdc12, was confirmed by quantitative real-time PCR. A protein array revealed that levels of IL-1β, G-CSF, GM-CSF, CXCL1, CXCL2, CXCL9 and CCL2 were increased in Tgm1–/–skin. Epidermal growth factor receptor (EGFR) ligand genes, Hbegf, Areg and Ereg, were activated in Tgm1–/–epidermis. Furthermore, the antimicrobial activity of an epidermal extract from Tgm1–/–mice was significantly increased against both Escherichia coli and Staphylococcus aureus. In the epidermis of ichthyosiform skins from patients with TGM1 mutations, S100A8/9 was strongly positive. The expression of those antimicrobial and defense response genes was also increased in the lesional skin of an ARCI patient with TGM1 mutations. These results suggest that the up-regulation of molecular signatures for antimicrobial and innate defense responses is characteristic of skin with a transglutaminase 1 deficiency, and this autonomous process might be induced to reinforce the defective barrier function of the skin. PMID:27442430

  13. The role of Probiotics in allergic diseases

    PubMed Central

    Michail, Sonia

    2009-01-01

    Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders. PMID:19946408

  14. Regulatory T cells in allergic diseases.

    PubMed

    Noval Rivas, Magali; Chatila, Talal A

    2016-09-01

    The pathogenesis of allergic diseases entails an ineffective tolerogenic immune response to allergens. Regulatory T (Treg) cells play a key role in sustaining immune tolerance to allergens, yet mechanisms by which Treg cells fail to maintain tolerance in patients with allergic diseases are not well understood. We review current concepts and established mechanisms regarding how Treg cells regulate different components of allergen-triggered immune responses to promote and maintain tolerance. We will also discuss more recent advances that emphasize the "dual" functionality of Treg cells in patients with allergic diseases: how Treg cells are essential in promoting tolerance to allergens but also how a proallergic inflammatory environment can skew Treg cells toward a pathogenic phenotype that aggravates and perpetuates disease. These advances highlight opportunities for novel therapeutic strategies that aim to re-establish tolerance in patients with chronic allergic diseases by promoting Treg cell stability and function. PMID:27596705

  15. 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

  16. Skin lumps

    MedlinePlus

    ... and contains fluid or semisolid material Benign skin growths such as seborrheic keratoses or neurofibromas Boils , painful, red bumps usually involving an infected hair follicle Corn or callus, caused by skin thickening in response ...

  17. Active skin perfusion and thermoregulatory response in the hand following nerve injury and repair in human upper extremities.

    PubMed

    Deng, Aidong; Liu, Dan; Gu, Chen; Gu, Xiaosong; Gu, Jianhui; Hu, Wen

    2016-01-01

    Cutaneous vasoconstriction/vasodilatation occurs in response to whole body and local cooling/heating, and the vasomotor activities play a pivotal role in thermal control of the human body. The mechanisms underlying regulation of skin blood flow involve both neurogenic and humeral/local chemical influence, contributing to the initial response to thermal stimuli and the prolonged phase of response, respectively. Previous studies have suggested the impairment of cutaneous thermal regulation after nerve injury. However, the evidence regarding how the skin perfusion and thermoregulatory response evolve after nerve injury and repair remains limited. Here we observed, by utilizing laser-Doppler perfusion imaging, baseline skin perfusion and perfusion change in response to thermal stimuli after median and ulnar nerve injury, and the results showed that baseline perfusion in autonomous skin area profoundly decreased and active rewarming after clod stress dramatically diminished before sensory recovery of the skin became detectable. In addition, baseline cutaneous perfusion was recovered as the skin regained touch sensation, and exhibited positive correlation to touch sensibility of the skin. These data indicate that both active perfusion and thermoregulatory response of the skin are markedly compromised during skin denervation and can be recovered by re-innervation. This suggests the importance of timely repair of injured nerve, especially in the practice of replantation. PMID:26529641

  18. The innate and adaptive response to mosquito saliva and Plasmodium sporozoites in the skin.

    PubMed

    Hopp, Christine S; Sinnis, Photini

    2015-04-01

    A malaria infection begins when an infected mosquito takes a blood meal and inoculates parasites into the skin of its mammalian host. The parasite then has to exit the skin and escape the immune cells that protect the body from infection and alert the system to intruding pathogens. It has become apparent that this earliest stage of infection is amenable to vaccine interventions. Here, we discuss how the innate and adaptive host response to both mosquito saliva and the parasite may interfere with the infection, as well as possible mechanisms the parasite might use to circumvent the host defense. PMID:25694058

  19. Mechanical response of porcine skin under compression from low to high strain rates

    NASA Astrophysics Data System (ADS)

    Bo, Chiara; Butler, Ben; Williams, Alun; Brown, Katherine; Proud, William

    2013-06-01

    Uniaxial compression experiments were performed on fresh porcine skin samples at different strain rates to study the stress-strain response. Low strain rate experiments were performed with an Instron 5566, while high strain rates were achieved using a Split Hopkinson Pressure Bar system. Magnesium bars and semiconductor strain gauges were used respectively to maximize the signal transmission from porcine skin to the output bar and to allow the signal measurement. Skin samples were harvested from different area of the animal to investigate the heterogeneity of such material. The experimental results showed that the mechanical response of skin in compression is strongly dependent on the strain rate of loading and on the location from which the samples were collected. Specimens collected from the rump showed a stiffer response compared to samples harvested from the thigh. Finally, a histological analysis of the samples post compression was carried out to examine the extent of tissue damage as a function of strain rate. This work is supported by the Atomic Weapons Establishment, UK and The Royal British Legion Centre for Blast Injury Studies at Imperial College London, UK.

  20. Enhanced immune responses by skin vaccination with influenza subunit vaccine in young hosts.

    PubMed

    Koutsonanos, Dimitrios G; Esser, E Stein; McMaster, Sean R; Kalluri, Priya; Lee, Jeong-Woo; Prausnitz, Mark R; Skountzou, Ioanna; Denning, Timothy L; Kohlmeier, Jacob E; Compans, Richard W

    2015-09-01

    Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could benefit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of influenza vaccine with vaccination by the conventional intramuscular route. Young mice that received 5 μg of H1N1 A/Ca/07/09 influenza subunit vaccine using MN demonstrated an improved serum antibody response (IgG1 and IgG2a) when compared to the young IM group, accompanied by higher numbers of influenza-specific antibody secreting cells (ASCs) in the bone marrow. In addition, we observed increased activation of follicular helper T cells and formation of germinal centers in the regional lymph nodes in the MN immunized group, rapid clearance of the virus from their lungs as well as complete survival, compared with partial protection observed in the IM-vaccinated group. Our results support the hypothesis that influenza vaccine delivery through the skin would be beneficial for protecting the high-risk young population from influenza infection. PMID:25744228

  1. Non-Invasive Optical Imaging of Eosinophilia during the Course of an Experimental Allergic Airways Disease Model and in Response to Therapy

    PubMed Central

    Markus, M. Andrea; Dullin, Christian; Mitkovski, Miso; Prieschl-Grassauer, Eva; Epstein, Michelle M.; Alves, Frauke

    2014-01-01

    Background Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils. Methodology/Principal Findings An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h–72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs. Conclusion/Significance We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time. PMID:24587190

  2. High-power femtosecond-terahertz pulse induces a wound response in mouse skin

    PubMed Central

    Kim, Kyu-Tae; Park, Jaehun; Jo, Sung Jin; Jung, Seonghoon; Kwon, Oh Sang; Gallerano, Gian Piero; Park, Woong-Yang; Park, Gun-Sik

    2013-01-01

    Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. Although a thorough assessment to predict potential concerns has to precede before practical utilization of THz source, the biological effect of THz radiation is not yet fully understood with scant related investigations. Here, we applied a femtosecond-terahertz (fs-THz) pulse to mouse skin to evaluate non-thermal effects of THz radiation. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly mediated by transforming growth factor-beta (TGF-β) signaling pathways. We validated NFκB1- and Smad3/4-mediated transcriptional activation in fs-THz-irradiated skin by chromatin immunoprecipitation assay. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of TGF-β. These findings suggest that fs-THz radiation initiate a wound-like signal in skin with increased expression of TGF-β and activation of its downstream target genes, which perturbs the wound healing process in vivo. PMID:23907528

  3. High-power femtosecond-terahertz pulse induces a wound response in mouse skin

    NASA Astrophysics Data System (ADS)

    Kim, Kyu-Tae; Park, Jaehun; Jo, Sung Jin; Jung, Seonghoon; Kwon, Oh Sang; Gallerano, Gian Piero; Park, Woong-Yang; Park, Gun-Sik

    2013-08-01

    Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. Although a thorough assessment to predict potential concerns has to precede before practical utilization of THz source, the biological effect of THz radiation is not yet fully understood with scant related investigations. Here, we applied a femtosecond-terahertz (fs-THz) pulse to mouse skin to evaluate non-thermal effects of THz radiation. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly mediated by transforming growth factor-beta (TGF-β) signaling pathways. We validated NFκB1- and Smad3/4-mediated transcriptional activation in fs-THz-irradiated skin by chromatin immunoprecipitation assay. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of TGF-β. These findings suggest that fs-THz radiation initiate a wound-like signal in skin with increased expression of TGF-β and activation of its downstream target genes, which perturbs the wound healing process in vivo.

  4. The electromagnetic response of human skin in the millimetre and submillimetre wave range

    NASA Astrophysics Data System (ADS)

    Feldman, Yuri; Puzenko, Alexander; Ben Ishai, Paul; Caduff, Andreas; Davidovich, Issak; Sakran, Fadi; Agranat, Aharon J.

    2009-06-01

    Recent studies of the minute morphology of the skin by optical coherence tomography revealed that the sweat ducts in human skin are helically shaped tubes, filled with a conductive aqueous solution. This, together with the fact that the dielectric permittivity of the dermis is higher than that of the epidermis, brings forward the supposition that as electromagnetic entities, the sweat ducts could be regarded as low Q helical antennas. The implications of this statement were further investigated by electromagnetic simulation and experiment of the in vivo reflectivity of the skin of subjects under varying physiological conditions (Feldman et al 2008 Phys. Rev. Lett. 100 128102). The simulation and experimental results are in a good agreement and both demonstrate that sweat ducts in the skin could indeed behave as low Q antennas. Thus, the skin spectral response in the sub-Terahertz region is governed by the level of activity of the perspiration system and shows the minimum of reflectivity at some frequencies in the frequency band of 75-110 GHz. It is also correlated to physiological stress as manifested by the pulse rate and the systolic blood pressure. As such, it has the potential to become the underlying principle for remote sensing of the physiological parameters and the mental state of the examined subject.

  5. The electromagnetic response of human skin in the millimetre and submillimetre wave range.

    PubMed

    Feldman, Yuri; Puzenko, Alexander; Ben Ishai, Paul; Caduff, Andreas; Davidovich, Issak; Sakran, Fadi; Agranat, Aharon J

    2009-06-01

    Recent studies of the minute morphology of the skin by optical coherence tomography revealed that the sweat ducts in human skin are helically shaped tubes, filled with a conductive aqueous solution. This, together with the fact that the dielectric permittivity of the dermis is higher than that of the epidermis, brings forward the supposition that as electromagnetic entities, the sweat ducts could be regarded as low Q helical antennas. The implications of this statement were further investigated by electromagnetic simulation and experiment of the in vivo reflectivity of the skin of subjects under varying physiological conditions (Feldman et al 2008 Phys. Rev. Lett. 100 128102). The simulation and experimental results are in a good agreement and both demonstrate that sweat ducts in the skin could indeed behave as low Q antennas. Thus, the skin spectral response in the sub-Terahertz region is governed by the level of activity of the perspiration system and shows the minimum of reflectivity at some frequencies in the frequency band of 75-110 GHz. It is also correlated to physiological stress as manifested by the pulse rate and the systolic blood pressure. As such, it has the potential to become the underlying principle for remote sensing of the physiological parameters and the mental state of the examined subject. PMID:19430110

  6. Role of β-TrCP ubiquitin ligase receptor in UVB mediated responses in skin

    PubMed Central

    Bhatia, Neehar; Demmer, Tara A.; Sharma, Alok K.; Elcheva, Irina; Spiegelman, Vladimir S.

    2011-01-01

    Skin cancers are the most common cancers in the United States. Exposure to UVB radiation is a major risk factor for skin cancer induction. SCFβ-TrCP E3 ubiquitin ligase has been found to be involved in cell cycle, cell proliferation and transformation. Aberrant up-regulation of beta-transducin repeats-containing proteins (β-TrCP) is often found in cancer cell lines and primary tumors. We have previously demonstrated that β-TrCP2 is over-expressed in chemically induced mouse skin tumors [1]. Various cellular stress stimuli, including UVB, induce an increase in β-TrCP1 mRNA and protein levels in human cells [2]. We have previously shown that inhibition of β-TrCP function, by induction of dominant negative β-TrCP2 (β-TrCP2ΔF), in vitro in hTERT immortalized normal keratinocytes, results in increase in UVB induced apoptosis [3]. We have generated transgenic mice with inducible, selective expression of dominant negative β-TrCP2 in epidermis with the Keratin 5 promoter (K5-rTA × TRE-HA-β-TrCPΔF). Here we report that inhibition of β-TrCP function in mouse epidermis results in decrease in UVB-induced edema, hyperplasia, and inflammatory response and increment in UVB-induced apoptosis in skin. Our results suggest that β-TrCP may be an essential player in UVB induced responses in skin and can be a potential therapeutic target for skin cancer. PMID:21187057

  7. Parallel intraindividual evaluation of the vasoconstrictory action and the anti-allergic activity of topical corticosteroids.

    PubMed

    Seidenari, S; Di Nardo, A; Mantovani, L; Giannetti, A

    1997-04-01

    The human skin blanching assay is a well established method for ranking the efficacy of corticosteroids after epicutaneous application. Vasoconstriction is a pharmacological activity, which correlates well with the clinical efficacy, the intensity of skin blanching after a single application under occlusion corresponding, generally, to the clinical efficacy after repeated application without occlusion. However, in studies dealing with the comparison between the vasoconstriction assay and the evaluation of the clinical effects on inflammatory skin diseases, some exceptions to this correlation have been reported. Therefore, in a pre-clinical phase, it would be useful to combine the blanching assay with at least one anti-inflammatory assay. In the present study the blanching assay and the allergic contact dermatitis inhibition test were performed in parallel, in order to compare the two testing procedures in the same group of subjects, utilizing standardized study designs supported by objective means of evaluation. Three commercial preparations of corticosteroids containing clobetasol propionate (CP), clobetasone butyrate (CB) and hydrocortisone acetate (HA), respectively, were employed both to treat nickel-induced positive patch test responses on the volar forearms, and to perform a vasoconstrictor assay on normal forearm skin in 16 nickel-sensitized healthy volunteers. For evaluating skin blanching, we employed colorimetric measurements, whereas for the quantitative determination of the inhibition of the intensity of allergic patch test reactions, 20 MHz B-scanning supported by image analysis was used. Both colorimetric and echogenicity values enabled us to distinguish between the three corticosteroids (at the 17 h evaluation and the 64 h assessment, respectively). A fair correlation was noted between colorimetric and echogenicity values. Both testing procedures ranked the three corticosteroids in the expected order. Corticosteroid preparations should be compared

  8. Neutrophil recruitment by allergens contribute to allergic sensitization and allergic inflammation

    PubMed Central

    Hosoki, Koa; Boldogh, Istvan; Sur, Sanjiv

    2016-01-01

    Purpose of review To discuss the presence and role of neutrophils in asthma and allergic diseases, and outline importance of pollen and cat dander-induced innate neutrophil recruitment in induction of allergic sensitization and allergic inflammation. Recent findings Uncontrolled asthma is associated with elevated numbers of neutrophils, and levels of neutrophil-attracting chemokine IL-8 and IL-17 in BAL fluids. These parameters negatively correlate with lung function. Pollen allergens and cat dander recruit neutrophils to the airways in a TLR4, MD2 and CXCR2-dependent manner. Repeated recruitment of activated neutrophils by these allergens facilitates allergic sensitization and airway inflammation. Inhibition of neutrophil recruitment with CXCR2 inhibitor, disruption of TLR4, or siRNA against MD2 also inhibits allergic inflammation. The molecular mechanisms by which neutrophils shift the inflammatory response of the airways to inhaled allergens to an allergic phenotype is an area of active research. Summary Recent studies have revealed that neutrophil recruitment is important in development of allergic sensitization and inflammation. Inhibition of neutrophils recruitment may be strategy to control allergic inflammation. PMID:26694038

  9. 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

  10. Functional Specialization of Skin Dendritic Cell Subsets in Regulating T Cell Responses

    PubMed Central

    Clausen, Björn E.; Stoitzner, Patrizia

    2015-01-01

    Dendritic cells (DC) are a heterogeneous family of professional antigen-presenting cells classically recognized as most potent inducers of adaptive immune responses. In this respect, Langerhans cells have long been considered to be prototypic immunogenic DC in the skin. More recently this view has considerably changed. The generation of in vivo cell ablation and lineage tracing models revealed the complexity of the skin DC network and, in particular, established the existence of a number of phenotypically distinct Langerin+ and negative DC populations in the dermis. Moreover, by now we appreciate that DC also exert important regulatory functions and are required for the maintenance of tolerance toward harmless foreign and self-antigens. This review summarizes our current understanding of the skin-resident DC system in the mouse and discusses emerging concepts on the functional specialization of the different skin DC subsets in regulating T cell responses. Special consideration is given to antigen cross-presentation as well as immune reactions toward contact sensitizers, cutaneous pathogens, and tumors. These studies form the basis for the manipulation of the human counterparts of the murine DC subsets to promote immunity or tolerance for the treatment of human disease. PMID:26557117

  11. Novel delivery systems for anti-allergic agents: allergic disease and innovative treatments.

    PubMed

    Lopes, Carla M; Coelho, Pedro B; Oliveira, Rita

    2015-01-01

    Anti-allergic agents are used to treat a great variety of diseases which usually involve an inflammation reaction. These compounds act by inhibiting the release and the effects of inflammatory mediators (e.g. histamine) in the target tissue. The purpose of anti-allergy therapy is to deliver the drug to its local of action in a therapeutic concentration, minimizing the undesired side effects. In order to solve some of the anti-allergic agents' physicochemical drawbacks and the limitations associated to conventional pharmaceutical formulations (e.g. poor solubility and absorption, skin permeation, stability), novel drug delivery systems, such as cyclodextrins, liposomes, micelles, microemulsions, nano and microparticles, have been developed. Depending on the allergic condition, several administration routes are used to deliver anti-allergic agents, each with its own disadvantages to overcome. In the literature, there are a vast number of papers concerning novel delivery systems for anti-allergic agents, making it difficult to evaluate the information and the promising outcomes. The aim of the present review article is to compile the recent (i.e. in the new millennium) improvements of novel drug delivery technology focusing on the achievement of anti-allergic therapeutic delivery. The potential intrinsic benefits of these systems will reflect an increased therapeutic adherence and better patients' life quality. A critical prospect of future clinical trial directions will also be discussed. PMID:25895551

  12. An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice

    SciTech Connect

    Lee, Jun Ho; Kim, Tae Hyung; Kim, Hyuk Soon; Kim, A-Ram; Kim, Do-Kyun; Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Her, Erk; Park, Yeong Min; Kim, Hyung Sik; Kim, Young Mi; Choi, Wahn Soo

    2015-06-15

    Mast cells, constituents of virtually all organs and tissues, are critical cells in IgE-mediated allergic responses. The aim of this study was to investigate the effect and mechanism of an indoxyl chromogenic compound, 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, on IgE-mediated mast cell activation and allergic responses in mice. CAC-0982 reversibly suppressed antigen-stimulated degranulation in murine mast cells (IC{sub 50}, ~ 3.8 μM) and human mast cells (IC{sub 50}, ~ 3.0 μM). CAC-0982 also inhibited the expression and secretion of IL-4 and TNF-α in mast cells. Furthermore, CAC-0982 suppressed the mast cell-mediated allergic responses in mice in a dose-dependent manner (ED{sub 50} 27.9 mg/kg). As for the mechanism, CAC-0982 largely suppressed the phosphorylation of Syk and its downstream signaling molecules, including LAT, Akt, Erk1/2, p38, and JNK. Notably, the tyrosine kinase assay of antigen-stimulated mast cells showed that CAC-0982 inhibited Fyn kinase, one of the upstream tyrosine kinases for Syk activation in mast cells. Taken together, these results suggest that CAC-0982 may be used as a new treatment for regulating IgE-mediated allergic diseases through the inhibition of the Fyn/Syk pathway in mast cells. - Highlights: • The anti-allergic effect of 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, was measured. • CAC-0982 reversibly suppressed the activation of mast cells by IgE and antigen. • CAC-0982 inhibited passive cutaneous anaphylaxis in mice. • CAC-0982 suppresses mast cells through inhibition of Fyn activation in mast cells.

  13. Reactivity of allergy skin test in healthy volunteers

    PubMed Central

    Supakthanasiri, Phisit; Klaewsongkram, Jettanong; Chantaphakul, Hiroshi

    2014-01-01

    INTRODUCTION Healthy individuals may be exposed and sensitised to allergens, and have a positive response to a skin prick test despite being asymptomatic. The objectives of this study were to evaluate the prevalence of atopic sensitisation and identify the reactivity of healthy volunteers to common aeroallergens. METHODS Healthy volunteers with no known allergic symptoms were recruited in this study. All volunteers were scheduled to undergo a skin prick test with 16 common aeroallergens that were previously identified among atopic patients. RESULTS A total of 100 volunteers (mean age 28 years) were enrolled in this study. 42 volunteers had positive skin prick tests for at least one allergen. The median number of sensitised allergen was 2 (range 1–7). Volunteers with positive skin tests (n = 42) were younger than those with negative skin tests (n = 58) (mean age 25.5 vs. 29.2 years; p < 0.05). The group with positive skin tests also had a higher proportion of males (57.1% vs. 31.0%; p < 0.01) and first-degree relatives with a history of atopic diseases (31.0% vs. 10.3%; p < 0.05). The most common sensitised allergens in these healthy asymptomatic volunteers were mite (n = 33), house dust (n = 23) and American cockroach (n = 20). CONCLUSION In this study, up to 42% of healthy volunteers, particularly those with a family history of atopy, were sensitised to allergens. Reactivity of the skin test without allergic symptoms, however, does not indicate allergic disease. Therefore, the skin test should only be indicated in atopic symptomatic individuals. PMID:24452975

  14. Halting the allergic march.

    PubMed

    Van Bever, Hugo P; Samuel, Sudesh T; Lee, Bee Wah

    2008-04-01

    The prevalence of childhood allergic diseases, such as allergic asthma, allergic rhinitis, and atopic dermatitis, has increased exponentially. In Singapore, the prevalence of asthma at all ages exceeds 20%, and around 50% of Singaporean children show features of an underlying allergy. The exact environmental causes for the increase of allergic diseases have not yet been identified, but most researchers agree that a decreased bacterial load in young children may be one of the reasons for the increase. However, the causes of allergy are multiple, and the development of an allergic disease is the result of complex interactions between genetic constitution and environmental factors. In this review article, different aspects of allergic sensitization are covered, including prenatal and postnatal sensitization. The phenomenon of the "allergic march" (switching from one clinical expression of allergy to another) and its underlying mechanisms are discussed. The last part of this review article is on prevention and treatment of allergic diseases, including the role of bacterial products (probiotics, prebiotics, and synbiotics) and the role of immunotherapy, including sublingual immunotherapy. PMID:23283392

  15. Molecular characterization of human skin response to diphencyprone at peak and resolution phases: therapeutic insights.

    PubMed

    Gulati, Nicholas; Suárez-Fariñas, Mayte; Fuentes-Duculan, Judilyn; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; Correa da Rosa, Joel; Cueto, Inna; Mitsui, Hiroshi; Krueger, James G

    2014-10-01

    Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. It is used as an immune-modulating therapeutic, but its molecular effects in human skin are largely unknown. We studied cellular and molecular characteristics of a recall response to 0.04% DPCP at 3-day (peak) and 14-day (resolution) time points using immune markers, reverse-transcriptase-PCR (RT-PCR), and gene array approaches. A peak response showed modulation of ∼7,500 mRNA transcripts, with high expression of cytokines that define all major effector T-cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC) infiltrates were measured. The resolution reaction was characterized by unexpectedly high levels of T cells and mature (DC-lysosome-associated membrane glycoprotein positive (DC-LAMP+)) DCs, but with marked decreases in expression of IL-2, IFNγ, and other T cell-derived cytokines. However, negative immune regulators such as IDO1 that were high in peak reactions, continued to have high expression in resolution reactions. In the resolution reaction, ∼1,500 mRNA transcripts were significantly different from placebo-treated skin. These data suggest that the response to DPCP evolves from an inflammatory/effector peak at day 3 to a more regulated immune response after 14 days. This model system could be useful for further dissection of mechanisms of immune activation or negative immune regulation in human skin. PMID:24751728

  16. Molecular characterization of human skin response to diphencyprone at peak and resolution phases: therapeutic insights

    PubMed Central

    Gulati, Nicholas; Suárez-Fariñas, Mayte; Fuentes-Duculan, Judilyn; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; da Rosa, Joel Correa; Cueto, Inna; Mitsui, Hiroshi; Krueger, James G.

    2014-01-01

    Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. It is used as an immune modulating therapeutic, but its molecular effects in human skin are largely unknown. We studied cellular and molecular characteristics of a recall response to 0.04% DPCP at 3 day (peak) and 14 day (resolution) timepoints using immune markers, RT-PCR and gene array approaches. A peak response showed modulation of ~7,500 mRNA transcripts, with high expression of cytokines that define all major effector T-cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC) infiltrates were measured. The resolution reaction was characterized by unexpectedly high levels of T-cells and mature (DC-LAMP+) DCs, but with marked decreases in expression of IL-2, IFNγ, and other T-cell derived cytokines. However, negative immune regulators such as IDO1 that were high in peak reactions, continued to have high expression in resolution reactions. In the resolution reaction, ~1,500 mRNA transcripts were significantly different from placebo-treated skin. These data suggest the response to DPCP evolves from an inflammatory/effector peak at day 3 to a more regulated immune response after 14 days. This model system could be useful for further dissection of mechanisms of immune activation or negative immune regulation in human skin. PMID:24751728

  17. Evidence-based practice: sublingual immunotherapy for allergic rhinitis.

    PubMed

    Wise, Sarah K; Schlosser, Rodney J

    2012-10-01

    In this article, the authors review the current evidence regarding the public health and economic impact of allergic rhinitis. Diagnostic methods for allergic disease are discussed as well as certain nuances of allergy skin testing protocols. In addition, the evidence supporting sublingual immunotherapy (SLIT) for allergic rhinitis is reviewed, with subsequent attention to certain subgroups, such as adults and children, seasonal versus perennial allergens, and SLIT efficacy for individual antigens. The authors consider the evidence supporting appropriate SLIT dosing as well as the existing data on SLIT safety. PMID:22980684

  18. 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

  19. Allergic contact dermatitis due to a herbicide (barban).

    PubMed Central

    Hogan, D J; Lane, P R

    1985-01-01

    Canadian farmers are using increasing amounts of herbicides. Often they do not use adequate skin protection. Two cases of severe allergic contact dermatitis due to the herbicide barban are described. Patch testing with various substances, including barban, confirmed the diagnosis. Sensitization studies in guinea pigs and in one of the authors showed that barban is a potent sensitizer. It is recommended that if skin contact with barban occurs the skin be washed immediately with soap and water. Images Fig. 1 PMID:3971254

  20. Elevated local skin temperature impairs cutaneous vasoconstrictor responses to a simulated haemorrhagic challenge while heat stressed

    PubMed Central

    Pearson, J.; Lucas, R. A. I.; Crandall, C. G.

    2016-01-01

    During a simulated haemorrhagic challenge, syncopal symptoms develop sooner when individuals are hyperthermic relative to normothermic. This is due, in part, to a large displacement of blood to the cutaneous circulation during hyperthermia, coupled with inadequate cutaneous vasoconstriction during the hypotensive challenge. The influence of local skin temperature on these cutaneous vasoconstrictor responses is unclear. This project tested the hypothesis that local skin temperature modulates cutaneous vasoconstriction during simulated haemorrhage in hyperthermic humans. Eight healthy participants (four men and four women; 32 ± 7 years old; 75.2 ± 10.8 kg) underwent lower-body negative pressure to presyncope while heat stressed via a water-perfused suit sufficiently to increase core temperature by 1.2 ± 0.2°C. At forearm skin sites distal to the water-perfused suit, local skin temperature was either 35.2 ± 0.6 (mild heating) or 38.2 ± 0.2°C (moderate heating) throughout heat stress and lower-body negative pressure, and remained at these temperatures until presyncope. The reduction in cutaneous vascular conductance during the final 90 s of lower-body negative pressure, relative to heat-stress baseline, was greatest at the mildly heated site (−10 ± 15% reduction) relative to the moderately heated site (−2 ± 12%; P = 0.05 for the magnitude of the reduction in cutaneous vascular conductance between sites), because vasoconstriction at the moderately heated site was either absent or negligible. In hyperthermic individuals, the extent of cutaneous vasoconstriction during a simulated haemorrhage can be modulated by local skin temperature. In situations where skin temperature is at least 38°C, as is the case in soldiers operating in warm climatic conditions, a haemorrhagic insult is unlikely to be accompanied by cutaneous vasoconstriction. PMID:22903981

  1. [Development of allergic reactivity to Artemesia pollen during combined sensitization to pollen and microbes].

    PubMed

    Ermekova, R K

    1978-08-01

    Some regularities of formation of hypersensitivity of the immediate type to the pollen of Artemisia absinthium were studied under conditions of combined hypersensitivity to pollen and Brucella abortus 19-BA vaccine strain; the latter was administered 3, 12, and 28 days after the pollen. The degree of specific allergic reconstruction to the pollen was studied by passive skin anaphylaxis after Ovary, indirect degranulation of mast cells of healthy rats, and by general anaphylaxis in response to intravenous injection of the Artemisia absinthium pollen water-salt extract. Early formation of allergy to the pollen was observed in the groups of animals with combined hypersensitivity to the pollen and brucellae. The degree of allergic reactivity to the pollen allergen was more expressed in the groups with combined allergy than in those with pure pollen hypersensitivity at all the stages of this experiment. PMID:99195

  2. Allergic and asthmatic reactions to alcoholic drinks.

    PubMed

    Vally, Hassan; Thompson, Philip J

    2003-03-01

    Alcoholic drinks are capable of triggering a wide range of allergic and allergic-like responses, including rhinitis, itching, facial swelling, headache, cough and asthma. Limited epidemiological data suggests that many individuals are affected and that sensitivities occur to a variety of drinks, including wine, beer and spirits. In surveys of asthmatics, over 40% reported the triggering of allergic or allergic-like symptoms following alcoholic drink consumption and 30 - 35% reported worsening of their asthma. Sensitivity to ethanol itself can play a role in triggering adverse responses, particularly in Asians, which is due mainly to a reduced capacity to metabolize acetaldehyde. In Caucasians, specific non-alcohol components are the main cause of sensitivities to alcoholic drinks. Allergic sensitivities to specific components of beer, spirits and distilled liquors have been described. Wine is clearly the most commonly reported trigger for adverse responses. Sensitivities to wine appear to be due mainly to pharmacological intolerances to specific components, such as biogenic amines and the sulphite additives. Histamine in wine has been associated with the triggering of a wide spectrum of adverse symptoms, including sneezing, rhinitis, itching, flushing, headache and asthma. The sulphite additives in wine have been associated with triggering asthmatic responses. Clinical studies have confirmed sensitivities to the sulphites in wine in limited numbers of individuals, but the extent to which the sulphites contribute to wine sensitivity overall is not clear. The aetiology of wine-induced asthmatic responses may be complex and may involve several co-factors. PMID:12745410

  3. Immediate skin responses to laser and light treatments: Therapeutic endpoints: How to obtain efficacy.

    PubMed

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Chan, Henry H; Alam, Murad; Tannous, Zeina; Anderson, R Rox

    2016-05-01

    Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints. PMID:27085228

  4. Pollen-induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis.

    PubMed

    Desai, Mauli B; Gavrilova, Tatyana; Liu, Jianjun; Patel, Shyam A; Kartan, Saritha; Greco, Steven J; Capitle, Eugenio; Rameshwar, Pranela

    2013-10-01

    Mesenchymal stem cells (MSCs) are promising cellular suppressor of inflammation. This function of MSCs is partly due to their licensing by inflammatory mediators. In cases with reduced inflammation, MSCs could become immune-enhancer cells. MSCs can suppress the inflammatory response of antigen-challenged lymphocytes from allergic asthma. Although allergic rhinitis (AR) is also an inflammatory response, it is unclear if MSCs can exert similar suppression. This study investigated the immune effects (suppressor vs enhancer) of MSCs on allergen-stimulated lymphocytes from AR subjects (grass or weed allergy). In contrast to subjects with allergic asthma, MSCs caused a significant (P<0.05) increase in the proliferation of antigen-challenged lymphocytes from AR subjects. The increase in lymphocyte proliferation was caused by the MSCs presenting the allergens to CD4(+) T cells (antigen-presenting cells (APCs)). This correlated with increased production of inflammatory cytokines from T cells, and increased expressions of major histocompatibility complex (MHC)-II and CD86 on MSCs. The specificity of APC function was demonstrated in APC assay using MSCs that were knocked down for the master regulator of MHC-II transcription, CIITA. The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests. Thus, we deduced that the contrasting immune effects of MSCs for antigen-challenged lymphocytes on AR and allergic asthma could be disease specific. It is possible that the enhanced inflammation from asthma might be required to license the MSCs to become suppressor cells. This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder. PMID:25505949

  5. Regulatory T Cells Modulate Th17 Responses in Tuberculin skin test positive (TST+) individuals

    PubMed Central

    Babu, Subash; Bhat, Sajid Q.; Kumar, N. Pavan; Kumaraswami, V.; Nutman, Thomas B.

    2009-01-01

    Background The factors governing latency in tuberculosis (TB) are not well understood but appear to include pathogen and host factors. We have used Tuberculin skin test positivity as a tool to study cytokine responses in latent TB. Methods To identify host factors important in maintenance of TST positivity, we examined mycobacteria-specific immune responses of tuberculin skin test positive (TST+; latent TB) or negative (TST−; healthy) individuals in South India where skin test positivity can define TB latency. Results While PPD- and Mycobacterium tuberculosis culture filtrate Ag-specific Th1 and Th2 cytokines were not significantly different between the two groups, the Th17 cytokines—IL-17 and IL-23—were significantly decreased in TST+ individuals compared with the TST− individuals. This Th17 cytokine modulation was associated with significantly increased expression of CTLA-4 and Foxp3. Although CTLA-4 blockade failed to restore full production of IL-17 and IL-23 in TST+ individuals, depletion of regulatory T cells significantly increased production of these cytokines. Conclusion TST positivity is characterized by increased activity of regulatory T cells and a coincident downregulation of the Th17 response. PMID:19929695

  6. Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness.

    PubMed

    Chren, M M; Lasek, R J; Quinn, L M; Mostow, E N; Zyzanski, S J

    1996-11-01

    To measure the effects of skin disease on patients' quality of life, we developed a 61-item self-administered survey instrument called Skindex. Skindex has eight scales, each of which addresses a construct, or an abstract component, in a comprehensive conceptual framework: cognitive effects, social effects, depression, fear, embarrassment, anger, physical discomfort, and physical limitations. Item responses are standardized from 0 (no effect) to 100 (maximal effect); a scale score is the average of responses to items addressing a construct. In 201 patients seen by dermatologists, mean scale scores (+/-SD) ranged from 14 (+/-17) for physical limitations to 31 (+/-22) for physical discomfort. Scale scores were reproducible after 72 h (r = 0.68-0.90) and were internally consistent (Cronbach's alpha = 0.76-0.86). Construct validity was assessed in two ways: (i) in a comparison of patients with inflammatory dermatoses and patients with isolated lesions, patients with inflammatory dermatoses had higher scale scores, and (ii) in an exploratory factor analysis, 78% of the common variance was explained by seven factors that correlated with the scale scores of Skindex. Most of the a priori scale scores changed in the expected direction in patients who reported that their skin conditions had improved or worsened after 6 mo. Finally, physicians' judgments of disease severity did not consistently correlate with Skindex scores. These preliminary data suggest that Skindex reliably and responsively measures the effects of skin disease on patients' quality of life and may supplement clinical judgments of disease severity. PMID:8875954

  7. The effect of the moisture content of a local heat source on the blood flow response of the skin.

    PubMed

    Petrofsky, Jerrold Scott; Bains, Gurinder; Raju, Chinna; Lohman, Everett; Berk, Lee; Prowse, Michelle; Gunda, Shashi; Madani, Piyush; Batt, Jennifer

    2009-09-01

    Numerous studies have examined the effect of local and global heating of the body on skin blood flow. However, the effect of the moisture content of the heat source on the skin blood flow response has not been examined. Thirty-three subjects, without diabetes or cardiovascular disease, between the ages of 22 and 32 were examined to determine the relationship between the effects of dry vs. moist heat applied for the same length of time and with the skin clamped at the same skin temperature on the blood flow response of the skin. The skin, heated with an infrared heat lamp (skin temperature monitored with a thermocouple) to 40 degrees C for 15 min, was either kept moist with wet towels or, in a separate experiment, kept dry with Drierite (a desiccant) between the towels to remove any moisture. Before and after heat exposure of the forearm, blood pressure, heart rate, skin moisture content, skin temperature, and skin blood flow were recorded. The results of the experiment showed that there was no change in skin moisture after 15 min exposure to dry heat at 40 degrees C. However, with moist heat, skin moisture increased by 43.7%, a significant increase (P < 0.05). With dry heat, blood flow increased from the resting value by 282.3% whereas with moist heat, blood flow increased by 386% over rest, a significant increase over dry heat (P < 0.05). Thus, with a set increase in skin temperature, moist heat was a better heating modality than dry heat. The reason may be linked to moisture sensitivity in calcium channels in the vascular endothelial cell. PMID:19415313

  8. α-Tocopherol supplementation of allergic female mice inhibits development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates

    PubMed Central

    Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Soveg, Frank W.

    2014-01-01

    α-Tocopherol blocks responses to allergen challenge in allergic adult mice, but it is not known whether α-tocopherol regulates the development of allergic disease. Development of allergic disease often occurs early in life. In clinical studies and animal models, offspring of allergic mothers have increased responsiveness to allergen challenge. Therefore, we determined whether α-tocopherol blocked development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with α-tocopherol starting at mating. The pups from allergic mothers developed allergic lung responses, whereas pups from saline-treated mothers did not respond to the allergen challenge, and α-tocopherol supplementation of allergic female mice resulted in a dose-dependent reduction in eosinophils in the pup bronchoalveolar lavage and lungs after allergen challenge. There was also a reduction in pup lung CD11b+ dendritic cell subsets that are critical to development of allergic responses, but there was no change in several CD11b− dendritic cell subsets. Furthermore, maternal supplementation with α-tocopherol reduced the number of fetal liver CD11b+ dendritic cells in utero. In the pups, there was reduced allergen-induced lung mRNA expression of IL-4, IL-33, TSLP, CCL11, and CCL24. Cross-fostering pups at the time of birth demonstrated that α-tocopherol had a regulatory function in utero. In conclusion, maternal supplementation with α-tocopherol reduced fetal development of subsets of dendritic cells that are critical for allergic responses and reduced development of allergic responses in pups from allergic mothers. These results have implications for supplementation of allergic mothers with α-tocopherol. PMID:25015974

  9. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    PubMed

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation. PMID:25445491

  10. Intestinal Microbiota Promotes Psoriasis-Like Skin Inflammation by Enhancing Th17 Response

    PubMed Central

    Zákostelská, Zuzana; Málková, Jana; Klimešová, Klára; Rossmann, Pavel; Hornová, Michaela; Novosádová, Iva; Stehlíková, Zuzana; Kostovčík, Martin; Hudcovic, Tomáš; Štepánková, Renata; Jůzlová, Kateřina; Hercogová, Jana; Tlaskalová-Hogenová, Helena

    2016-01-01

    Psoriasis is a chronic inflammatory skin disease in which Th17 cells play a crucial role. Since indigenous gut microbiota influences the development and reactivity of immune cells, we analyzed the link among microbiota, T cells and the formation of psoriatic lesions in the imiquimod-induced murine model of psoriasis. To explore the role of microbiota, we induced skin inflammation in germ-free (GF), broad-spectrum antibiotic (ATB)-treated or conventional (CV) BALB/c and C57BL/6 mice. We found that both mice reared in GF conditions for several generations and CV mice treated with ATB were more resistant to imiquimod-induced skin inflammation than CV mice. The ATB treatment dramatically changed the diversity of gut bacteria, which remained stable after subsequent imiquimod application; ATB treatment resulted in a substantial increase in the order Lactobacillales and a significant decrease in Coriobacteriales and Clostridiales. Moreover, as compared to CV mice, imiquimod induced a lower degree of local and systemic Th17 activation in both GF and ATB-treated mice. These findings suggest that gut microbiota control imiquimod-induced skin inflammation by altering the T cell response. PMID:27434104

  11. Immunologic principles of allergic disease.

    PubMed

    Averbeck, Marco; Gebhardt, Carl; Emmrich, Frank; Treudler, Regina; Simon, Jan C

    2007-11-01

    Allergy either results from a pathological excessive immune reaction, or from the defective induction of tolerance to otherwise harmless antigens. Allergic reactions are mounted by mechanisms of innate and adaptive immunity. The development of an allergic response can be divided in sensitization and elicitation phases. Immediate type allergic reactions (e.g. anaphylaxis, urticaria, rhinoconjunctivitis allergica, allergic asthma) are mediated by IgE antibodies which are produced by B cells stimulated by allergen-specific Th2 cells. Crosslinking of allergen-specific IgE on membrane surfaces of mast cells and basophilic granulocytes leads to release of soluble mediators which may cause systemic symptoms within minutes to hours. The following infiltration of eosinophilic granulocytes and Th2 cells directs chronic inflammation. Humoral cytotoxic immune reactions (e.g. drug induced cytopenia) are mediated by IgG and IgM antibodies which are directed against membrane associated antigens. IgG and IgM antibodies directed against soluble antigens elicit immune complex mediated cytotoxicity (e.g.drug induced vasculitis). Delayed type immune reactions (e.g.contact dermatitis) are based on the activation of antigen specific CD4(+) and CD8(+) T cells and need 24 h to 48 h to develop. Upon recurrent contact with identical antigens, recruitment of CD4(+) and CD8(+) T cells cause inflammation and cytotoxic induced apoptosis in target cells as well as cytokine mediated leukocyte infiltration. Subsequent immigration of CD4(+) Th2 cells provides anti-inflammatory mechanisms leading to resolution of the inflammatory response and tissue repair. PMID:17976144

  12. Tryptophan Metabolism in Allergic Disorders.

    PubMed

    Gostner, Johanna M; Becker, Katrin; Kofler, Heinz; Strasser, Barbara; Fuchs, Dietmar

    2016-01-01

    Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-x03B3; (IFN-x03B3;). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may

  13. The effects of cordycepin on ovalbumin-induced allergic inflammation by strengthening Treg response and suppressing Th17 responses in ovalbumin-sensitized mice.

    PubMed

    Tianzhu, Zhang; Shihai, Yang; Juan, Du

    2015-01-01

    The aim of the current study was to use a mouse model of allergic asthma to investigate whether cordycepin has antiasthmatic effects, and if so, to determine the mechanism of these effects. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (Dex, 2 mg/kg), and cordycepin (20-40 mg/kg). Histological studies were evaluated by the hematoxylin and eosin staining, OVA-specific serum and BALF IgE levels and Treg/Th17 cytokines were evaluated by enzyme-linked immunosorbent assay, and RORγt and Foxp3 were evaluated by western blot. Our study demonstrated that cordycepin inhibited OVA-induced increases in eosinophil count; IL-17A levels were recovered and increased IL-10 levels in bronchoalveolar lavage fluid. Histological studies demonstrated that cordycepin substantially inhibited OVA-induced eosinophilia in lung tissue. Western blot study demonstrated that cordycepin increased Foxp3 and inhibited RORγt. These findings suggest that cordycepin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma. PMID:25417131

  14. Thermographic assessment of skin prick tests in comparison with the routine evaluation methods

    PubMed Central

    Rokita, Eugeniusz; Tatoń, Grzegorz; Guzik, Tomasz; Śliwa, Tomasz

    2016-01-01

    Introduction The skin prick test is still the first and basic procedure in the diagnosis of allergic diseases. The possibility of using a sensitive thermographic method supported by the mathematical model for the assessment of skin test results will be highlighted in the studies. Aim To compare the proposed approach with routine planimetric and thermographic methods. Material and methods A mathematical model of allergic reaction was developed. Simplifying assumptions of the IgE-mediated skin reaction is the essence of the model. Investigations were performed in a group of 40 patients. Results Using the spatio-temporal evolution of temperature distributions, the ratios of the histamine released from mast cells to the control histamine were determined. The obtained values very well correlate with the standard evaluation of skin prick tests (correlation coefficient = 0.98). Conclusions The proposed method of skin test evaluation presents several advantages. The continuous acquisition of data provides the monitoring of time course of the allergic response. The transport of mediator and its concentration were distinctly discriminated, which may be diagnostically useful, especially for abnormal cases. The high sensitivity of the method enables studying patients regardless of age and skin sensitivity. PMID:27512354

  15. Whole-body heating decreases skin vascular response to low orthostatic stress in the lower extremities.

    PubMed

    Yamazaki, Fumio; Nakayama, Yoshiro; Sone, Ryoko

    2006-04-01

    To elucidate the influence of heat stress on cutaneous vascular response in the lower extremities during orthostatic stress, a head-up tilt (HUT) test at angles of 15 degrees, 30 degrees, 45 degrees, and 60 degrees for 4 min each was conducted under normothermic control conditions followed by whole-body heat stress produced by a hot water-perfused suit in healthy volunteers. Skin blood flows (SkBF) in the forearm, thigh, and calf were monitored using laser-Doppler flowmetry throughout the experiment. Furthermore, to elucidate the effects of increased core and local skin temperatures on the local vascular response in calf skin under increasing orthostatic stress, the thigh was occluded at 20, 30, 50, 70, and 80 mmHg with a cuff in both the normothermic condition and the whole-body or local heating condition. Significant decreases in forearm SkBF during HUT were observed at an angle of 60 degrees during normothermia and at 30 degrees or more during heating. SkBF in the thigh and calf was decreased significantly by HUT at 15 degrees and above during normothermia, and there was no significant reduction of SkBF in these sites during HUT at the lower angles (15 degrees -45 degrees ) during whole-body heating. Significant decreases of calf SkBF were observed at cuff pressures of 20 mmHg and above during normothermia and of 30 mmHg and above during whole-body and local heating, respectively. These results suggest that SkBF in the lower extremities shows a marked reduction compared with the upper extremities during low orthostatic stress in normothermia, and the enhanced skin vasoconstrictor response in the lower extremities is diminished by both whole-body and local heat stress. PMID:16839449

  16. Regional variations of skin blood flow response to histamine: evaluation by spectrophotometry and laser Doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Tur, Ethel; Aviram, Guy; Zeltser, D.; Brenner, Sarah; Maibach, Howard I.

    1996-01-01

    To study inherent differences in skin function related to regional variation, we tested the hypothesis that different reactivities of small blood vessels via their direct and indirect activation by histamine play an important role in the observed regional variation of processes. Histamine was administered to three cutaneous regions in 20 volunteers, and the induced response was quantified utilizing spectrophotometry and laser Doppler flowmetry. The back exhibited the greatest response, followed by the forearm and ankle in decreasing order of responsiveness. We suggest that the intensity of the wheal and flare response may partly be related to the local reactivity of the blood vessels once the histamine actually reached them, and to their indirect dilatation via the axonal reflex. These blood vessel response observations may provide initial insight into inherent functional differences influencing cutaneous manifestations of endogenous and exogenous diseases.

  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. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    SciTech Connect

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.

    2012-12-01

    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  19. Mechanisms of DNA damage response to targeted irradiation in organotypic 3D skin cultures.

    PubMed

    Acheva, Anna; Ghita, Mihaela; Patel, Gaurang; Prise, Kevin M; Schettino, Giuseppe

    2014-01-01

    DNA damage (caused by direct cellular exposure and bystander signaling) and the complex pathways involved in its repair are critical events underpinning cellular and tissue response following radiation exposures. There are limited data addressing the dynamics of DNA damage induction and repair in the skin particularly in areas not directly exposed. Here we investigate the mechanisms regulating DNA damage, repair, intracellular signalling and their impact on premature differentiation and development of inflammatory-like response in the irradiated and surrounding areas of a 3D organotypic skin model. Following localized low-LET irradiation (225 kVp X-rays), low levels of 53BP1 foci were observed in the 3D model (3.8±0.28 foci/Gy/cell) with foci persisting and increasing in size up to 48 h post irradiation. In contrast, in cell monolayers 14.2±0.6 foci/Gy/cell and biphasic repair kinetics with repair completed before 24 h was observed. These differences are linked to differences in cellular status with variable level of p21 driving apoptotic signalling in 2D and accelerated differentiation in both the directly irradiated and bystander areas of the 3D model. The signalling pathways utilized by irradiated keratinocytes to induce DNA damage in non-exposed areas of the skin involved the NF-κB transcription factor and its downstream target COX-2. PMID:24505255

  20. A dose-response analysis of skin cancer from inorganic arsenic in drinking water

    SciTech Connect

    Brown, K.G.; Boyle, K.E.; Chen, C.W.; Gibb, H.J. )

    1989-12-01

    A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3)) if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).

  1. Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses.

    PubMed

    Sawada, Yu; Honda, Tetsuya; Hanakawa, Sho; Nakamizo, Satoshi; Murata, Teruasa; Ueharaguchi-Tanada, Yuri; Ono, Sachiko; Amano, Wataru; Nakajima, Saeko; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Kitoh, Akihiko; Dainichi, Teruki; Ogawa, Narihito; Kobayashi, Yuichi; Yokomizo, Takehiko; Arita, Makoto; Nakamura, Motonobu; Miyachi, Yoshiki; Kabashima, Kenji

    2015-10-19

    Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID:26438363

  2. Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

    PubMed Central

    Sawada, Yu; Hanakawa, Sho; Nakamizo, Satoshi; Murata, Teruasa; Ueharaguchi-Tanada, Yuri; Ono, Sachiko; Amano, Wataru; Nakajima, Saeko; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Kitoh, Akihiko; Dainichi, Teruki; Ogawa, Narihito; Kobayashi, Yuichi; Yokomizo, Takehiko; Arita, Makoto; Nakamura, Motonobu; Miyachi, Yoshiki

    2015-01-01

    Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID:26438363

  3. [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

  4. Management of allergic Olympic athletes.

    PubMed

    Fitch, K D

    1984-05-01

    Twenty percent of the recent Australian Olympic athletes have had an allergic disorder. Because of the ban on all sympathomimetic drugs except some beta 2-agonists. Olympic team physicians have a major responsibility to ensure that no competitor is disqualified for infringing on the antidoping rules of the Medical Commission of the International Olympic Committee. Inadvertent contravention of these regulations may occur because numerous banned sympathomimetics are available to athletes and their coaches without medical prescription and are frequently contained in combination preparations. The unbroken 24 yr in which asthmatics have won Olympic medals have been both before and after the introduction of drug tests. Currently a comprehensive range of preventive and therapeutic medications are available for asthmatics to compete with minimal respiratory disadvantage. It was, however, during a period of unnecessary restriction that an American swimmer forfeited his gold medal because of prerace ingestion of a banned sympathomimetic agent. Should adverse air quality be encountered during the Los Angeles Olympics, allergic competitors will be among the most inconvenienced . Athletes with allergic rhinitis and sinusitis will be the most disadvantaged because sympathomimetic vasoconstrictors remain banned. It is strongly recommended that the Medical Commission of the International Olympic Committee meet with an appropriate body of experts (i.e., the American Academy of Allergy and Immunology) to review this ban on vasoconstrictor agents. PMID:6715736

  5. Investigational drugs for allergic rhinitis.

    PubMed

    Passalacqua, Giovanni; Compalati, Enrico; Canonica, Giorgio Walter

    2010-01-01

    Allergic rhinitis (AR) is a high-prevalence disease, triggered by an IgE-mediated reaction, and sustained by a complex inflammatory network of cells, mediators, and cytokines. When the exposure to allergens persists, the inflammatory process becomes chronic. The current therapeutic strategy is based on allergen avoidance when possible, drugs and allergen immunotherapy. The main drugs are oral and topical antihistamines and nasal steroids. They are overall effective in controlling symptoms, but do not modify the immune background that leads to allergic inflammation. In addition, safety concerns may be present, especially for prolonged treatments. Thus, efforts are currently made to improve the existing molecules and to develop new drugs, in order to achieve greater clinical efficacy with a better tolerability. Also, attempts are made to selectively block relevant signal pathways of the allergic reaction by means of specific anti-mediators. Specific immunotherapy, in addition to the clinical effect, is capable of modifying the Th2-biased immune response. Thus, an intense research activity is presently ongoing with the aim of improving the characteristics and modes of action of this treatment. PMID:20001557

  6. Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations

    PubMed Central

    Iredahl, Fredrik; Löfberg, Andreas; Sjöberg, Folke; Farnebo, Simon; Tesselaar, Erik

    2015-01-01

    Introduction Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques. Method Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi. Results Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9±6.2 PU; 10-min 100±25 PU; p<0.001) and RBC concentration (TiVi: baseline 119±18; 10-min 150±41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0±4.4 PU; 10-min 38.9±5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6±11.8 AU; 10-min 54.4±13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8±3.6 PU; max 112±55 PU; p<0.001, LSCI: baseline 50.8±8.0 PU; max 151±22 PU; p<0.001) and RBC concentration (TiVi: baseline 49.2±32.9 AU; max 99.3±28.3 AU; p<0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: p<0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (p<0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses. Conclusion LSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline

  7. The importance of TSLP in allergic disease and its role as a potential therapeutic target

    PubMed Central

    Cianferoni, Antonella; Spergel, Jonathan

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine similar to IL- 7, whose gene is located on chromosome 5q22.1 and it exerts its biological function through the TSLP-Receptor (TSLP-R). TSLP is expressed primarily by epithelial cells at barrier surfaces such as the skin, gut and lung in response to danger signals. Since it was cloned in 1994, there has been accumulating evidence that TSLP is crucial for the maturation of antigen presenting cells and hematopoietic cells. TSLP genetic variants and its dysregulated expression have been linked to atopic diseases such as atopic dermatitis, asthma, allergic rhinitis and eosinophilic esophagitis. PMID:25340427

  8. [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. PMID:8115841

  9. The response of skin to applied stress: investigation of bitemark distortion in a cadaver model.

    PubMed

    Bush, Mary A; Thorsrud, Kyle; Miller, Raymond G; Dorion, Robert B J; Bush, Peter J

    2010-01-01

    Knowledge of distortional properties of skin is important in bitemark analysis. Thus, the response of skin to stress from bites was investigated. Four sets of models were created from the dentition of one individual. Anterior teeth were systematically removed to vary contact surface area. A biting apparatus was constructed with an integrated load cell. Forty-six bites were created perpendicular to Langer lines on six cadavers. Rate of force application and bite pressure were controlled. Metric/angular measurement and hollow volume overlays were employed. Distortion produced by each dentition was calculated and assessed. Results showed that as teeth impressed loose tissue, mesial/distal distance increased, angles of rotation flattened, and inter-canine distance lengthened. An opposite effect was seen in tight tissue. When the surface area of the dentition was reduced, a mixture of these effects was observed. Conclusions indicated that stiffness of the tissue was the most important variable in bitemark distortion. PMID:20002269

  10. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis.

    PubMed

    Chawes, Bo L K

    2011-05-01

    of the nasal mucosa in children already at age 6 years. Non-allergic rhinitis exhibited no change in the nasal airway patency, but some nasal eosinophilia albeit less than children with allergic rhinitis. These findings suggest different pathology in allergic- and non-allergic rhinitis which may have important clinical implications for early pharmacological treatment of rhinitis in young children. In paper II, we utilized the nasal airway patency end-points derived from paper I to examine whether upper and lower airway patency are associated. Upper airway patency was assessed by acoustic rhinometry before and after intranasal α-agonist and lower airway patency by spirometry before and after inhaled β2-agonist. Upper and lower airway patencies were strongly associated and independent of body size, rhinitis and asthma. The association was consistent for both baseline values and for decongested nasal airway patency and post-β2 FEV1. Blood and nasal eosinophilia were also associated with nasal airway obstruction. This suggests generalized diminished airway dimensions as a novel susceptibility factor for concurrent symptoms of asthma and rhinitis in early childhood and supports the notion of a common pathophysiology in asthma and rhinitis. The clinical interpretation of these findings is that all children presenting either rhinitis or asthma should be considered inflamed in the entire respiratory tract. In paper III, we aimed to describe asthma and intermediary asthma end-points associated with allergic- and non-allergic rhinitis in preschool-aged children. At age 7 years, we evaluated prevalence of asthma, eczema, food sensitization, and filaggrin mutations; levels of total IgE, FeNO, and blood-eosinophils; lung function and bronchial responsiveness to cold dry air. We found that asthma was similarly associated with allergic- and non-allergic rhinitis suggesting a link between upper and lower airway diseases beyond an allergy associated inflammation. Only children

  11. When Beauty Is Skin Deep: Regulation of the Wound Response by Caspase-8, RIPK3, and the Inflammasome.

    PubMed

    Vince, James E

    2015-08-01

    Caspase-8 downregulation is observed in the epidermis of wounded skin, whereas permanent epidermal caspase-8 deletion causes chronic skin inflammation, suggesting that caspase-8 is a critical regulator of skin homeostasis and, possibly, the wound response. In this issue, Lee et al. document how epidermal caspase-8 deletion, or cutaneous wounding, results in increased NF-κB activation to drive keratinocyte caspase-1 expression and subsequent secretion of the pro-inflammatory cytokines, IL-1β and IL-1α. Consequently, loss of NF-κB activity, caspase-1, or the IL-1 receptor delays wound healing. Previous studies have documented how chronic skin inflammation in caspase-8-deficient mice is rescued by RIPK3 co-deletion. Therefore, targeting caspase-1, IL-1, or RIPK3 itself may benefit treatment of chronic inflammatory skin diseases, or where an inappropriate inflammatory response proves detrimental to wound healing, such as in type 2 diabetes. PMID:26174535

  12. RESPIRATORY RESPONSES OF SUBJECTS WITH ALLERGIC RHINITIS TO OZONE EXPOSURE AND THEIR RELATIONSHIP TO NONSPECIFIC AIRWAY REACTIVITY

    EPA Science Inventory

    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 ozo...

  13. Allergic sensitization and the environment: latest update.

    PubMed

    Yoo, Young; Perzanowski, Matthew S

    2014-10-01

    The prevalence of asthma and other allergic diseases is still increasing both in developed and developing countries. Allergic sensitization against common inhalant allergens is common and, although not sufficient, a necessary step in the development of allergic diseases. Despite a small number of proteins from certain plants and animals being common allergens in humans, we still do not fully understand who will develop sensitization and to which allergens. Environmental exposure to these allergens is essential for the development of sensitization, but what has emerged clearly in the literature in the recent years is that the adjuvants to which an individual is exposed at the same time as the allergen are probably an equally important determinant of the immune response to the allergen. These adjuvants act on all steps in the development of sensitization from modifying epithelial barriers, to facilitating antigen presentation, to driving T-cell responses, to altering mast cell and basophil hyperreactivity. The adjuvants come from biogenic sources, including microbes and the plants and animals that produce the allergens, and from man-made sources (anthropogenic), including unintended by-products of combustion and chemicals now ubiquitous in modern life. As we better understand how individuals are exposed to these adjuvants and how the exposure influences the likelihood of an allergic response, we may be able to design individual and community-level interventions that will reverse the increase in allergic disease prevalence, but we are not there yet. PMID:25149167

  14. 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

  15. 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 ...

  16. 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

  17. 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 ...

  18. 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 ...

  19. Endothelial nitric oxide synthase G894T gene polymorphism and response to skin reactive hyperemia.

    PubMed

    Rasool, Aida Hanum Ghulam; Ghazali, Dzuzaini Mohd; Abdullah, Haswati; Halim, Ahmad Sukari; Wong, Abd Rahim

    2009-09-01

    Post occlusive skin reactive hyperemia (PORH) is a tool used to assess microcirculation. Endothelial nitric oxide synthase (eNOS) mediates nitric oxide (NO) production; polymorphism of the eNOS gene may affect response to the PORH process. This study aims to determine whether eNOS G894T gene polymorphism affects response to skin PORH. 230 normotensive male and females between 18 and 40 years participated in this cross-sectional study. 170 subjects were of the homozygous GG genotype, whereas 60 were of the GT genotype. Skin PORH was performed by occlusion of the upper arm at 200 mm Hg for 3 min. Skin perfusion and temperature were monitored before, during and after occlusion release using the laser Doppler fluximetry. There were no significant differences between genotypes in their baseline blood pressure, serum cholesterol, BMI and age. Maximum change in perfusion after occlusion release (PORHmax) for the GG and GT genotypes were not significantly different at 50.15+/-1.29 vs. 47.92+/-2.17 AU; ANCOVA, p=0.351. Peak perfusion (PORHpeak) were also not significantly different between the two genotypes (61.23+/-1.36 vs. 57.72+/-2.32 AU; p=0.169). Minimum baseline perfusion were however higher in the GG compared to the GT genotype (10.83+/-0.29 vs. 9.61+/-0.50, p=0.029). We conclude that microvascular reactivity, assessed by change in perfusion after temporary ischemia was not significantly different between the GG and GT genotypes of the eNOS G894T gene. eNOS 894T allele carriers however, have lower baseline perfusion compared to the homozygous G894 allele carrier. PMID:19481100

  20. Risk of allergic reactions to wine, in milk, egg and fish-allergic patients

    PubMed Central

    2011-01-01

    Background European legislators and wine producers still debate on the requirement for labeling of wines fined with potentially allergenic food proteins (casein, egg white or fish-derived isinglass). We investigated whether wines fined with known concentrations of these proteins have the potential to provoke clinical allergic reactions in relevant patients. Methods In-house wines were produced for the study, fined with different concentrations of casein (n = 7), egg albumin (n = 1) and isinglass (n = 3). ELISA and PCR kits specific for the respective proteins were used to identify the fining agents. Skin prick tests and basophil activation tests were performed in patients with confirmed IgE-mediated relevant food allergies (n = 24). A wine consumption questionnaire and detailed history on possible reactions to wine was obtained in a multinational cohort of milk, egg or fish allergic patients (n = 53) and patients allergic to irrelevant foods as controls (n = 13). Results Fining agents were not detectable in wines with the available laboratory methods. Nevertheless, positive skin prick test reactions and basophil activation to the relevant wines were observed in the majority of patients with allergy to milk, egg or fish, correlating with the concentration of the fining agent. Among patients consuming wine, reported reactions were few and mild and similar with the ones reported from the control group. Conclusion Casein, isinglass or egg, remaining in traces in wine after fining, present a very low risk for the respective food allergic consumers. Physician and patient awareness campaigns may be more suitable than generalized labeling to address this issue, as the latter may have negative impact on both non-allergic and allergic consumers. PMID:22409883

  1. [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

  2. Brief Report: "Allergic Symptoms" in Children with Autism Spectrum Disorders. More than Meets the Eye?

    ERIC Educational Resources Information Center

    Angelidou, Asimenia; Alysandratos, Konstantinos-Dionysios; Asadi, Shahrzad; Zhang, Bodi; Francis, Konstantinos; Vasiadi, Magdalini; Kalogeromitros, Dimitrios; Theoharides, Theoharis C.

    2011-01-01

    Many children with Autism Spectrum Disorders (ASD) have either family and/or personal history of "allergic symptomatology", often in the absence of positive skin or RAST tests. These symptoms may suggest mast cell activation by non-allergic triggers. Moreover, children with mastocytosis or mast cell activation syndrome (MCAS), a spectrum of rare…

  3. A study for characterization of IgE-mediated cutaneous immediate and late-phase reactions in non-allergic domestic cats.

    PubMed

    Seals, Shanna L; Kearney, Michael; Del Piero, Fabio; Hammerberg, Bruce; Pucheu-Haston, Cherie M

    2014-05-15

    Immunoglobulin-E (IgE) mediated reactions can be induced by intradermal injection of anti-IgE antibodies in both humans and dogs. These reactions grossly and histologically mimic changes seen in naturally occurring allergic dermatitis in these species. Similar studies have not been conducted in the cat. Purified polyclonal rabbit-origin IgG specific for canine IgE (anti-IgE) and rabbit immunoglobulin G (IgG) were injected intradermally in 7 non-allergic laboratory colony cats. Wheal measurements were obtained and biopsies collected before injection and at injection sites after 20 min, 6, 24, and 48 h. Injection of anti-IgE induced an immediate wheal response which was significantly larger than that seen after injection of rabbit IgG. Anti-IgE injected skin was also significantly thicker than IgG-injected skin. This corresponded with a significant increase in number of visibly degranulated mast cells in anti-IgE samples when compared to IgG samples. Injection of anti-IgE was associated with the rapid recruitment of inflammatory cells to the injected dermis. The number of inflammatory cells and mononuclear cells were significantly elevated after the injection of anti-IgE when compared to IgG-injected skin. Both eosinophils and neutrophils were significantly increased in anti-IgE samples relative to IgG, although neutrophils were only transiently increased. The high eosinophil and relatively low neutrophil cell counts in these samples were consistent with previously documented histologic features of naturally occurring feline allergic skin disease. Immunohistochemistry identified a significantly overall increased CD1a(+) cells after the intradermal injection of anti-IgE when compared to IgG and non-injected skin. CD3(+), CD8(+) and CD4(+) were also significantly increased overall in anti-IgE injected skin relative to IgG injected skin. These data document the gross and cellular response to injection of anti-IgE in the skin of healthy, non-allergic cats and support a

  4. Propranolol, a beta-adrenergic antagonist, retards response to MSH in skin of Anolis carolinensis.

    PubMed

    Vaughan, G L; Greenberg, N

    1987-01-01

    Lacking sympathetic innervation, the skin of A. carolinensis, an iguanid lizard, darkens within minutes in response to circulating melanocyte stimulating hormone (MSH) or beta adrenergic agonists such as epinephrine (EPI). This change is produced by dispersion of melanin from a perinculear position within dermal melanophores into superficial dendritic processes. These melanophores possess alpha-2 and beta-2 adrenergic as well as MSH receptors except in a patch of skin behind the eye, the eyespot, which lacks alpha receptors. Activation of beta or MSH receptors leads to stimulation of adenyl cyclase whereas alpha stimulation inhibits the enzyme to override the others. In a series of trials, injection of saline or propranolol was followed after 30 minutes by saline, EPI, or MSH. Propranolol inhibited chromatophore response to EPI. It also, unexpectedly, retarded the response to MSH, increasing latency to eyespot formation and body color change as well as the duration of darkening for both. Alteration of MSH response by a beta blocker could be explained by linkage of both adrenergic receptors and the MSH receptor to a common adenyl cyclase molecule to form a functional unit in the membrane of the melanophore. PMID:3671516

  5. Exposure to inhomogeneous static magnetic field beneficially affects allergic inflammation in a murine model

    PubMed Central

    Csillag, Anikó; Kumar, Brahma V.; Szabó, Krisztina; Szilasi, Mária; Papp, Zsuzsa; Szilasi, Magdolna E.; Pázmándi, Kitti; Boldogh, István; Rajnavölgyi, Éva; Bácsi, Attila; László, János F.

    2014-01-01

    Previous observations suggest that static magnetic field (SMF)-exposure acts on living organisms partly through reactive oxygen species (ROS) reactions. In this study, we aimed to define the impact of SMF-exposure on ragweed pollen extract (RWPE)-induced allergic inflammation closely associated with oxidative stress. Inhomogeneous SMF was generated with an apparatus validated previously providing a peak-to-peak magnetic induction of the dominant SMF component 389 mT by 39 T m−1 lateral gradient in the in vivo and in vitro experiments, and 192 mT by 19 T m−1 in the human study at the 3 mm target distance. Effects of SMF-exposure were studied in a murine model of allergic inflammation and also in human provoked skin allergy. We found that even a single 30-min exposure of mice to SMF immediately following intranasal RWPE challenge significantly lowered the increase in the total antioxidant capacity of the airways and decreased allergic inflammation. Repeated (on 3 consecutive days) or prolonged (60 min) exposure to SMF after RWPE challenge decreased the severity of allergic responses more efficiently than a single 30-min treatment. SMF-exposure did not alter ROS production by RWPE under cell-free conditions, while diminished RWPE-induced increase in the ROS levels in A549 epithelial cells. Results of the human skin prick tests indicated that SMF-exposure had no significant direct effect on provoked mast cell degranulation. The observed beneficial effects of SMF are likely owing to the mobilization of cellular ROS-eliminating mechanisms rather than direct modulation of ROS production by pollen NAD(P)H oxidases. PMID:24647908

  6. Do mouse models of allergic asthma mimic clinical disease?

    PubMed

    Epstein, Michelle M

    2004-01-01

    Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing (1). the factors influencing the pathophysiological responses during

  7. γ-Tocopherol supplementation of allergic female mice augments development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates.

    PubMed

    Abdala-Valencia, Hiam; Soveg, Frank; Cook-Mills, Joan M

    2016-04-15

    γ-Tocopherol increases responses to allergen challenge in allergic adult mice, but it is not known whether γ-tocopherol regulates the development of allergic disease. Development of allergic disease often occurs early in life. In clinical studies and animal models, offspring of allergic mothers have increased responsiveness to allergen challenge. Therefore, we determined whether γ-tocopherol augments development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with γ-tocopherol starting at mating. The pups from allergic mothers developed allergic lung responses, whereas pups from saline-treated mothers did not respond to allergen challenge. The γ-tocopherol supplementation of allergic female mice increased the numbers of eosinophils twofold in the pup bronchoalveolar lavage and lungs after allergen challenge. There was also about a twofold increase in pup lung CD11b(+) subsets of CD11c(+) dendritic cells and in numbers of these dendritic cells expressing the transcription factor IRF4. There was no change in several CD11b(-) dendritic cell subsets. Furthermore, maternal supplementation with γ-tocopherol increased the number of fetal liver CD11b(+)CD11c(+) dendritic cells twofold in utero. In the pups, γ-tocopherol increased lung expression of the inflammatory mediators CCL11, amphiregulin, activin A, and IL-5. In conclusion, maternal supplementation with γ-tocopherol increased fetal development of subsets of dendritic cells that are critical for allergic responses and increased development of allergic responses in pups from allergic mothers. These results have implications for supplementation of allergic mothers with γ-tocopherol in prenatal vitamins. PMID:26801566

  8. Raman spectroscopy: in vivo quick response code of skin physiological status

    NASA Astrophysics Data System (ADS)

    Vyumvuhore, Raoul; Tfayli, Ali; Piot, Olivier; Le Guillou, Maud; Guichard, Nathalie; Manfait, Michel; Baillet-Guffroy, Arlette

    2014-11-01

    Dermatologists need to combine different clinically relevant characteristics for a better understanding of skin health. These characteristics are usually measured by different techniques, and some of them are highly time consuming. Therefore, a predicting model based on Raman spectroscopy and partial least square (PLS) regression was developed as a rapid multiparametric method. The Raman spectra collected from the five uppermost micrometers of 11 healthy volunteers were fitted to different skin characteristics measured by independent appropriate methods (transepidermal water loss, hydration, pH, relative amount of ceramides, fatty acids, and cholesterol). For each parameter, the obtained PLS model presented correlation coefficients higher than R2=0.9. This model enables us to obtain all the aforementioned parameters directly from the unique Raman signature. In addition to that, in-depth Raman analyses down to 20 μm showed different balances between partially bound water and unbound water with depth. In parallel, the increase of depth was followed by an unfolding process of the proteins. The combinations of all these information led to a multiparametric investigation, which better characterizes the skin status. Raman signal can thus be used as a quick response code (QR code). This could help dermatologic diagnosis of physiological variations and presents a possible extension to pathological characterization.

  9. Raman spectroscopy: in vivo quick response code of skin physiological status.

    PubMed

    Vyumvuhore, Raoul; Tfayli, Ali; Piot, Olivier; Le Guillou, Maud; Guichard, Nathalie; Manfait, Michel; Baillet-Guffroy, Arlette

    2014-01-01

    Dermatologists need to combine different clinically relevant characteristics for a better understanding of skin health. These characteristics are usually measured by different techniques, and some of them are highly time consuming. Therefore, a predicting model based on Raman spectroscopy and partial least square (PLS) regression was developed as a rapid multiparametric method. The Raman spectra collected from the five uppermost micrometers of 11 healthy volunteers were fitted to different skin characteristics measured by independent appropriate methods (transepidermal water loss, hydration, pH, relative amount of ceramides, fatty acids, and cholesterol). For each parameter, the obtained PLS model presented correlation coefficients higher than R2=0.9. This model enables us to obtain all the aforementioned parameters directly from the unique Raman signature. In addition to that, in-depth Raman analyses down to 20 μm showed different balances between partially bound water and unbound water with depth. In parallel, the increase of depth was followed by an unfolding process of the proteins. The combinations of all these information led to a multiparametric investigation, which better characterizes the skin status. Raman signal can thus be used as a quick response code (QR code). This could help dermatologic diagnosis of physiological variations and presents a possible extension to pathological characterization. PMID:24839943

  10. RasGRP1 Transgenic Mice Develop Cutaneous Squamous Cell Carcinomas in Response to Skin Wounding

    PubMed Central

    Diez, Federico R.; Garrido, Ann A.; Sharma, Amrish; Luke, Courtney T.; Stone, James C.; Dower, Nancy A.; Cline, J. Mark; Lorenzo, Patricia S.

    2009-01-01

    Models of epidermal carcinogenesis have demonstrated that Ras is a critical molecule involved in tumor initiation and progression. Previously, we have shown that RasGRP1 increases the susceptibility of mice to skin tumorigenesis when overexpressed in the epidermis by a transgenic approach, related to its ability to activate Ras. Moreover, RasGRP1 transgenic mice develop spontaneous papillomas and cutaneous squamous cell carcinomas, some of which appear to originate in sites of injury, suggesting that RasGRP1 may be responding to signals generated during the wound-healing process. In this study, we examined the response of the RasGRP1 transgenic animals to full-thickness incision wounding of the skin, and demonstrated that they respond by developing tumors along the wounded site. The tumors did not present mutations in the H-ras gene, but Rasgrp1 transgene dosage correlated with tumor susceptibility and size. Analysis of serum cytokines showed increased levels of granulocyte colony-stimulating factor in transgenic animals after wounding. Furthermore, in vitro experiments with primary keratinocytes showed that granulocyte colony-stimulating factor stimulated Ras activation, although RasGRP1 was dispensable for this effect. Since granulocyte colony-stimulating factor has been recently associated with proliferation of skin cancer cells, our results may help in the elucidation of pathways that activate Ras in the epidermis during tumorigenesis in the absence of oncogenic ras mutations. PMID:19497993

  11. Host responses in human skin after conventional intradermal injection or microneedle administration of virus-like-particle influenza vaccine

    PubMed Central

    Pearton, Marc; Pirri, Daniela; Kang, Sang-Moo; Compans, Richard W; Birchall, James C

    2014-01-01

    Miniaturized microneedle devices are being developed for painlessly targeting vaccines to the immune cell populations in skin. As skin immunization studies are generally restricted to animal models however, where skin architecture and immunity is greatly different to human, surprisingly little is known about the local human response to intradermal (ID) vaccines. Here we use surgically excised human skin to explore for the first time the complex molecular and cellular host responses to a candidate influenza vaccine comprising nanoparticulate virus-like-particles (VLPs), administered via conventional hypodermic injection or reduced scale microneedles. Responses at the molecular level are determined by microarray analysis (47,296 discrete transcripts) and validated by quantitative PCR (96 genes). Cellular response is probed through monitoring migration of dendritic cells in viable skin tissue. Gene expression mapping, ontological analysis and qPCR reveal up-regulation of a host of genes responsible for key immunomodulatory processes and host viral response, including cell recruitment, activation, migration and T cell interaction following both ID and microneedle injection of VLPs; the response from the microneedles being more subtle. Significant morphological and migratory changes to skin dendritic cells are also apparent following microneedle VLP delivery. This is the first study displaying the global, multifaceted immunological events that occur at the site of vaccine deposition in human skin and will subsequently influence the degree and nature of innate and adaptive immune responses. An increased understanding of the detailed similarities and differences in response against antigen administered via different delivery modalities will inform the development of improved vaccines and vaccine delivery systems. PMID:23564440

  12. Impact of skin temperature and hydration on plasma volume responses during exercise.

    PubMed

    Kenefick, Robert W; Sollanek, Kurt J; Charkoudian, Nisha; Sawka, Michael N

    2014-08-15

    Heat stress and hydration may both alter plasma volume (PV) responses during acute exercise; potential interactions have not been fully studied. The purpose of this study was to determine the effect of graded elevations in skin temperature (Tsk) on PV changes during steady-state exercise under conditions of euhydration (EU) and hypohydration (HYPO, -4% of body mass). Thirty-two men (22 ± 4 yr) were divided into four cohorts (n = 8 each) and completed EU and HYPO trials in one environment [ambient temperature (Ta) 10, 20, 30, and 40°C]. Thirty minutes of cycle ergometry (50% V̇o2peak) was performed. Core (Tre) and mean skin (Tsk) temperatures were measured; changes in PV, total circulating protein (TCP), and mean arterial pressure (MAP) were calculated; and skin blood flow (SkBF) was estimated. Hypohydration decreased (P < 0.05) PV by 200 ml (-5.7%) but did not alter TCP. Plasma loss was not different between EU and HYPO during exercise at any Ta. Plasma losses were greater (P < 0.05) with elevated Ta with an average -130, -174, -294, and -445 ml losses during the 10, 20, 30, and 40°C trials, respectively. Significant (P < 0.05) correlations (r = 0.50 to 0.84) were found between ΔTCP and ΔPV during exercise when Tsk was cool/warm (<33°C; Ta 10, 20, and 30°C), but not at 40°C (high Tsk). We conclude that 1) graded skin warming proportionally accentuated plasma loss; 2) plasma loss was associated with plasma protein efflux at lower Tsk and SkBF; 3) at high Tsk, additional plasma loss likely results from increased net filtration at the capillaries; and 4) HYPO did not alter vascular fluid loss during exercise in any environment. PMID:24994888

  13. Biological and metabolic response in STS-135 space-flown mouse skin.

    PubMed

    Mao, X W; Pecaut, M J; Stodieck, L S; Ferguson, V L; Bateman, T A; Bouxsein, M L; Gridley, D S

    2014-08-01

    There is evidence that space flight condition-induced biological damage is associated with increased oxidative stress and extracellular matrix (ECM) remodeling. To explore possible mechanisms, changes in gene expression profiles implicated in oxidative stress and in ECM remodeling in mouse skin were examined after space flight. The metabolic effects of space flight in skin tissues were also characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Female C57BL/6 mice were flown in the STS-135 using animal enclosure modules (AEMs). Within 3-5 h after landing, the mice were euthanized and skin samples were harvested for gene array analysis and metabolic biochemical assays. Many genes responsible for regulating production and metabolism of reactive oxygen species (ROS) were significantly (p < 0.05) altered in the flight group, with fold changes >1.5 compared to AEM control. For ECM profile, several genes encoding matrix and metalloproteinases involved in ECM remodeling were significantly up-/down-regulated following space flight. To characterize the metabolic effects of space flight, global biochemical profiles were evaluated. Of 332 named biochemicals, 19 differed significantly (p < 0.05) between space flight skin samples and AEM ground controls, with 12 up-regulated and 7 down-regulated including altered amino acid, carbohydrate metabolism, cell signaling, and transmethylation pathways. Collectively, the data demonstrated that space flight condition leads to a shift in biological and metabolic homeostasis as the consequence of increased regulation in cellular antioxidants, ROS production, and tissue remodeling. This indicates that astronauts may be at increased risk for pathophysiologic damage or carcinogenesis in cutaneous tissue. PMID:24796731

  14. Effects and dose-response relationships of skin cancer and blackfoot disease with arsenic

    PubMed Central

    Tseng, Wen-Ping

    1977-01-01

    In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this “endemic” area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose–response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease. ImagesFIGURE 1.FIGURE 2. PMID:908285

  15. Biochemical and galvanic skin responses to music stimuli by college students in biology and music.

    PubMed

    VanderArk, S D; Ely, D

    1992-06-01

    The purpose of this study was to examine biochemical and physiological responses to musical stimuli. Specifically, university music and biology students' plasma levels of norepinephrine, endorphin, and cortisol, and their galvanic skin responses were measured before and after listening to two different musical selections in an anechoic chamber and during controlled silence. The results indicated that biochemical variables changed significantly in both groups during listening to music but were not different during the controlled silence. These data suggest that music majors may listen more analytically to music. GSR responses were significantly higher for music majors than biology majors, and plasma cortisol increased in music students but decreased in biology students. Music which elicits specific emotions induces physiological changes which may be beneficial to relaxation and behavioral therapies. PMID:1501973

  16. Regulating inflammation using acid-responsive electrospun fibrous scaffolds for skin scarless healing.

    PubMed

    Yuan, Ziming; Zhao, Jingwen; Chen, Yigang; Yang, Zhili; Cui, Wenguo; Zheng, Qi

    2014-01-01

    Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing. PMID:24795507

  17. Regulating Inflammation Using Acid-Responsive Electrospun Fibrous Scaffolds for Skin Scarless Healing

    PubMed Central

    Yuan, Ziming; Zhao, Jingwen; Chen, Yigang; Yang, Zhili; Zheng, Qi

    2014-01-01

    Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing. PMID:24795507

  18. Histone H3 Phosphorylation in Human Skin Histoculture as a Tool to Evaluate Patient’s Response to Antiproliferative Drugs

    PubMed Central

    Ugarte, Fernando; Porth, Katherine; Sadekova, Svetlana

    2015-01-01

    Evaluation of patient’s response to chemotherapeutic drugs is often difficult and time consuming. Skin punch biopsies are easily accessible material that can be used for the evaluation of surrogate biomarkers of a patient’s response to a drug. In this study, we hypothesized that assessment of phosphorylated histone H3 in human skin punch biopsies could be used as a pharmacodynamics biomarker of patient’s response to the kinesin spindle protein inhibitor SCH2047069. To test this hypothesis, we used a human skin histoculture technique that allows culturing intact human skin in the presence of the drug. Human melanoma and skin histocultures were treated with SCH2047069, and the effect of the drug was assessed by increasing histone H3 phosphorylation using immunohistochemistry. Our results demonstrate that SCH2047069 has a significant effect on cell proliferation in human melanoma and skin histoculture and justify using human skin punch biopsies for evaluation of the pharmacodynamic changes induced by SCH2047069. ACRONYMS Histone subunit H3 (H3), Kinesin spindle protein (KSP), 5-ethynyl-2′-deoxyuridine (EDU), Dimethyl sulfoxide (DMSO), Formalin-fixed paraffin embedded (FFPE). PMID:26917945

  19. Immediate skin responses to laser and light treatments: Warning endpoints: How to avoid side effects.

    PubMed

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Anderson, R Rox

    2016-05-01

    Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints. PMID:27085227

  20. Macrophage- and Neutrophil-Derived TNF-α Instructs Skin Langerhans Cells to Prime Antiviral Immune Responses

    PubMed Central

    Epaulard, Olivier; Adam, Lucille; Poux, Candice; Zurawski, Gerard; Salabert, Nina; Rosenbaum, Pierre; Dereuddre-Bosquet, Nathalie; Zurawski, Sandra; Flamar, Anne-Laure; Oh, Sangkon; Romain, Gabrielle; Chapon, Catherine; Banchereau, Jacques; Lévy, Yves; Le Grand, Roger; Martinon, Frédéric

    2014-01-01

    Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime immune responses. However, the roles of skin resident Langerhans cells (LCs) in eliciting immune responses have not been fully understood. We here demonstrate for the first time that LCs in cynomolgus macaque skin are capable of inducing antiviral-specific immune responses in vivo. Targeting HIV-Gag or influenza hemagglutinin antigens to skin LCs using recombinant fusion proteins of anti-Langerin antibody and antigens resulted in the induction of the viral antigen-specific responses. We further demonstrated that such antigen-specific immune responses elicited by skin LCs were greatly enhanced by TLR ligands (TLR-Ls), polyriboinosinic polyribocytidylic acid (poly(I:C)) and R848. These enhancements were not due to the direct actions of TLR-Ls on LCs, but mainly dependent on TNF-α secreted from macrophages and neutrophils recruited to local tissues. Skin LC activation and migration out of the epidermis are associated with macrophage and neutrophil infiltration into the tissues. More importantly, blocking TNF-α abrogated the activation and migration of skin LCs. This study highlights that the cross-talk between innate immune cells in local tissues is an important component for the establishment of adaptive immunity. Understanding the importance of local immune networks will help us to design new and effective vaccines against microbial pathogens. PMID:25057007

  1. Similar nociceptive afferents mediate psychophysical and electrophysiological responses to heat stimulation of glabrous and hairy skin in humans

    PubMed Central

    Iannetti, G D; Zambreanu, L; Tracey, I

    2006-01-01

    The ability to perceive and withdraw rapidly from noxious environmental stimuli is crucial for survival. When heat stimuli are applied to primate hairy skin, first pain sensation is mediated by type-II A-fibre nociceptors (II-AMHs). In contrast, the reported absence of first pain and II-AMH microneurographical responses when heat stimuli are applied to the hand palm has led to the notion that II-AMHs are lacking in this primate glabrous skin. The aim of this study was to assess the effect of hairy and glabrous skin stimulation on neural transmission of nociceptive inputs elicited by different kinds of thermal heating. We recorded psychophysical and EEG brain responses to radiant (laser-evoked potentials, LEPs) and contact heat stimuli (contact heat-evoked potentials, CHEPs) delivered to the dorsum and the palm of the hand in normal volunteers. Brain responses were analysed at a single-trial level, using an automated approach based on multiple linear regression. Laser stimulation of hairy and glabrous skin at the same energy elicited remarkably similar psychophysical ratings and LEPs. This finding provides strong evidence that first pain to heat does exist in glabrous skin, and suggests that similar nociceptive afferents, with the physiological properties of II-AMHs, mediate first pain to heat stimulation of glabrous and hairy skin in humans. In contrast, when contact heat stimuli were employed, a significantly higher nominal temperature had to be applied to glabrous skin in order to achieve psychophysical ratings similar to those obtained following hairy skin stimulation, and CHEPs following glabrous skin stimulation had significantly longer latencies (N2 wave, +25%; P2 wave, +24%) and smaller amplitudes (N2 wave, −40%; P2 wave, −44%) than CHEPs following hairy skin stimulation. Irrespective of the stimulated territory, CHEPs always had significantly longer latencies (hairy skin N2 wave, +75%; P2 wave, +56%) and smaller amplitudes (hairy skin N2 wave, −42%; P

  2. [Allergic bronchopulmonary aspergillosis. A report of a case and literature review].

    PubMed

    Meza Brítez, Ricardo L; del Río Navarro, Blanca E; Ochoa López, Georgina; Pietropaolo Cienfuegos, Dino; del Río Chivardi, Jaime M; Rosas Vargas, Miguel A

    2008-01-01

    Allergic bronchopulmonary aspergillosis is a world rare disease with a prevalence between 1 and 2%. It presents in moderate-severe asthma and cistic fibrosis patients. The diagnosis is made in the basis of Rossenberg and Greenberg criteria that can be essential or non essential. We present the case of a 3-year-old boy with allergic bronchopulmonary aspergillosis without bronchiectasies and with a good response to corticosteroids. His mother complained of two years of nasal obstruction, purulent rinorrea, nasal pruritus, sneezing, chronic cough and recurrent wheezing, twice to thrice a month. He also occasionally had vomits and diarrhea in relation with strawberries, banana, cow's milk and chocolate. We made the diagnosis of asthma, allergic rhinitis, sinusitis, and probably food allergy. We treated him with step approach of ICS according to GINA 2006, albuterol PRN, and elimination diet, with bad response. Laboratory exams: Blood white cells with eosinophilia (6%), total serum IgE: 1684 ng/L, aspergillus skin prick test: 4mm, serum IgG-Aspergillus fumigatus: 2.3 mcg/mL, serum IgE-Aspergillus fumigatus: negative, chest roentgenographic parahiliar and apical infiltrates, and chest computed tomography without bronchiectasies. We added prednisone to the treatment for four months, and we observed a very good response; he is now in treatment as mild persistent asthma with ICS low doses. ABPA must be suspected in patients with moderate-severe persistent asthma and a skin prick test positive to Aspergillus fumigatus regardless the age. The treatment with oral corticosteroids is the mainstream of management, and most of the patients have a good response, as we observed with this patient. PMID:19058490

  3. Allergic Rhinitis: Mechanisms and Treatment.

    PubMed

    Bernstein, David I; Schwartz, Gene; Bernstein, Jonathan A

    2016-05-01

    The prevalence of allergic rhinitis (AR) has been estimated at 10% to 40%, and its economic burden is substantial. AR patients develop specific immunoglobulin E (IgE) antibody responses to indoor and outdoor environmental allergens with exposure over time. These specific IgE antibodies bind to high-affinity IgE receptors on mast cells and basophils. Key outcome measures of therapeutic interventions include rhinitis symptom control, rescue medication requirements, and quality-of-life measures. A comprehensive multiple modality treatment plan customized to the individual patient can optimize outcomes. PMID:27083101

  4. In Vivo Assessment of Acute UVB Responses in Normal and Xeroderma Pigmentosum (XP-C) Skin-Humanized Mouse Models

    PubMed Central

    García, Marta; Llames, Sara; García, Eva; Meana, Alvaro; Cuadrado, Natividad; Recasens, Mar; Puig, Susana; Nagore, Eduardo; Illera, Nuria; Jorcano, José Luis; Del Rio, Marcela; Larcher, Fernando

    2010-01-01

    In vivo studies of UVB effects on human skin are precluded by ethical and technical arguments on volunteers and inconceivable in cancer-prone patients such as those affected with Xeroderma Pigmentosum (XP). Establishing reliable models to address mechanistic and therapeutic matters thus remains a challenge. Here we have used the skin-humanized mouse system that circumvents most current model constraints. We assessed the UVB radiation effects including the sequential changes after acute exposure with respect to timing, dosage, and the relationship between dose and degree-sort of epidermal alteration. On Caucasian-derived regenerated skins, UVB irradiation (800 J/m2) induced DNA damage (cyclobutane pyrimidine dimers) and p53 expression in exposed keratinocytes. Epidermal disorganization was observed at higher doses. In contrast, in African descent–derived regenerated skins, physiological hyperpigmentation prevented tissue alterations and DNA photolesions. The acute UVB effects seen in Caucasian-derived engrafted skins were also blocked by a physical sunscreen, demonstrating the suitability of the system for photoprotection studies. We also report the establishment of a photosensitive model through the transplantation of XP-C patient cells as part of a bioengineered skin. The inability of XP-C engrafted skin to remove DNA damaged cells was confirmed in vivo. Both the normal and XP-C versions of the skin-humanized mice proved proficient models to assess UVB-mediated DNA repair responses and provide a strong platform to test novel therapeutic strategies. PMID:20558577

  5. Cooling reduces the cutaneous afferent firing response to vibratory stimuli in glabrous skin of the human foot sole.

    PubMed

    Lowrey, Catherine R; Strzalkowski, Nicholas D J; Bent, Leah R

    2013-02-01

    Skin on the foot sole plays an important role in postural control. Cooling the skin of the foot is often used to induce anesthesia to determine the role of skin in motor and balance control. The effect of cooling on the four classes of mechanoreceptor in the skin is largely unknown, and thus the aim of the present study was to characterize the effects of cooling on individual skin receptors in the foot sole. Such insight will better isolate individual receptor contributions to balance control. Using microneurography, we recorded 39 single nerve afferents innervating mechanoreceptors in the skin of the foot sole in humans. Afferents were identified as fast-adapting (FA) or slowly adapting (SA) type I or II (FA I n = 16, FA II n = 7, SA I n = 6, SA II n = 11). Receptor response to vibration was compared before and after cooling of the receptive field (2-20 min). Overall, firing response was abolished in 30% of all receptors, and this was equally distributed across receptor type (P = 0.69). Longer cooling times were more likely to reduce firing response below 50% of baseline; however, some afferent responses were abolished with shorter cooling times (2-5 min). Skin temperature was not a reliable indicator of the level of receptor activation and often became uncoupled from receptor response levels, suggesting caution in the use of this parameter as an indicator of anesthesia. When cooled, receptors preferentially coded lower frequencies in response to vibration. In response to a sustained indentation, SA receptors responded more like FA receptors, primarily coding "on-off" events. PMID:23155170

  6. Optimisation of gelatin extraction from Unicorn leatherjacket (Aluterus monoceros) skin waste: response surface approach.

    PubMed

    Hanjabam, Mandakini Devi; Kannaiyan, Sathish Kumar; Kamei, Gaihiamngam; Jakhar, Jitender Kumar; Chouksey, Mithlesh Kumar; Gudipati, Venkateshwarlu

    2015-02-01

    Physical properties of gelatin extracted from Unicorn leatherjacket (Aluterus monoceros) skin, which is generated as a waste from fish processing industries, were optimised using Response Surface Methodology (RSM). A Box-Behnken design was used to study the combined effects of three independent variables, namely phosphoric acid (H3PO4) concentration (0.15-0.25 M), extraction temperature (40-50 °C) and extraction time (4-12 h) on different responses like yield, gel strength and melting point of gelatin. The optimum conditions derived by RSM for the yield (10.58%) were 0.2 M H3PO4 for 9.01 h of extraction time and hot water extraction of 45.83 °C. The maximum achieved gel strength and melting point was 138.54 g and 22.61 °C respectively. Extraction time was found to be most influencing variable and had a positive coefficient on yield and negative coefficient on gel strength and melting point. The results indicated that Unicorn leatherjacket skins can be a source of gelatin having mild gel strength and melting point. PMID:25694708

  7. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    SciTech Connect

    Ogami, M; Kulkarni, R; Wang, H; Reif, R; Wang, R K

    2014-08-31

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing. (laser biophotonics)

  8. Responses in rectal and skin temperatures to centrifugal forces in rats of different ambient temperatures

    NASA Astrophysics Data System (ADS)

    Ohara, K.; Sato, H.; Okuda, N.; Makino, Y.; Isobe, Y.

    1982-03-01

    Effects of centrifugation upon rectal (Tre) and tail skin temperatures (Ts) were studied in male Wistar rats at varying ambient temperature (Ta) using a centrifuge which was placed in a climatic chamber. Centrifugal forces of Gz of 3.0 were imposed on rats which were suspended at horizontal body position using a newly developed mesh suits holding method in the animal box placed on the rotating arm of the centrifuge. Headwards or tailwards forces were applied according to the experimental design. No significant difference of the responses was observed between the two force directions. Centrifugations imposed at different Ta of 15, 20, 25, 30 and 32.5‡C resulted in falls in Tre accompanied by rises in tail Ts at the cooler environments, while rises in Tre accompanied by falls in Ts in the warmer environments. The Ta at which the response pattern of Tre and Ts was reversed (critical ambient temperature) was 26.8±2.3 (mean and SE) and 27.9±2.8‡C, respectively. Tolerance to centrifugation was markedly increased in cooler environments than in wanner ones. It was suggested that the increased skin pressure due to centrifugation exerted some inhibitory effects upon central thermoregulatory ability.

  9. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    NASA Astrophysics Data System (ADS)

    Ogami, M.; Kulkarni, R.; Wang, H.; Reif, R.; Wang, R. K.

    2014-08-01

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing.

  10. Effect of 6'-acetylpaeoniflorin on dinitrochlorobenzene-induced allergic contact dermatitis in BALB/c mice.

    PubMed

    Zhou, Peng; Yang, Xiaodan; Jia, Xiaoyi; Yu, Jun; Asenso, James; Xiao, Feng; Wang, Chun; Wei, Wei

    2016-08-01

    Allergic contact dermatitis (ACD) is a classical experimental model of allergic inflammatory skin disease, which is a delayed-type hypersensitivity reaction that is mediated by hapten-specific T lymphocytes. The goal of this study was to investigate the pharmacokinetic profiles of 6'-acetylpaeoniflorin (6-AP) and the effect of 6-AP on the ACD model. 6-AP was synthesized from paeoniflorin (Pae) via acetylation, and the structure was confirmed. There were statistically significant differences in the pharmacokinetic parameters including t 1/2α , t 1/2β , AUC, MRT and C max among the animals that were orally administered Pae and 6-AP. An ACD model was induced using immunization with dinitrochlorobenzene (DNCB) in BALB/c mice. The mice were orally administered 6-AP (35, 70 and 140 mg/kg/d), Pae (70 mg/kg/d) and prednisone (Pre, 5 mg/kg/d) from day 1 to day 7 after immunization. The results indicated that the topical application of DNCB to the skin provoked obvious inflammatory responses. 6-AP significantly inhibited ear swelling and decreased inflammatory cell infiltration and epidermal keratinization. Additionally, 6-AP observably alleviated the hyperplasia of red pulp and germinal center appearance, decreased the spleen index and inhibited splenocyte proliferation in the ACD model compared to that of Pae. Furthermore, the study indicated that 6-AP could increase the IL-10 level, while simultaneously reducing the IL-17 level in splenocytes. In summary, these results suggest that 6-AP has a significantly higher anti-inflammatory effect than Pae and that 6-AP might be a candidate for the treatment of allergic skin diseases. PMID:26798038

  11. Allergic rhinitis - self-care

    MedlinePlus

    ... in something you are allergic to, such as dust mites, animal dander, or pollen. Allergic rhinitis is ... your or your child's exposure to them. Reduce dust and dust mites in the home. Control molds ...

  12. 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 ...

  13. Eosinophilic pleural effusion complicating allergic bronchopulmonary aspergillosis.

    PubMed

    Kirschner, Austin N; Kuhlmann, Erica; Kuzniar, Tomasz J

    2011-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is primarily a disease of patients with cystic fibrosis or asthma, who typically present with bronchial obstruction, fever, malaise, and expectoration of mucus plugs. We report a case of a young man with a history of asthma who presented with cough, left-sided pleuritic chest pain and was found to have lobar atelectasis and an eosinophilic, empyematous pleural effusion. Bronchoscopy and sputum cultures grew Aspergillus fumigatus, and testing confirmed strong allergic response to this mold, all consistent with a diagnosis of ABPA. This novel and unique presentation of ABPA expands on the differential diagnosis of eosinophilic pleural effusions. PMID:21311176

  14. 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

  15. Molecular genetic response of Xiphophorus maculatus-X. couchianus interspecies hybrid skin to UVB exposure.

    PubMed

    Lu, Yuan; Bowswell, Mikki; Bowswell, William; Yang, Kuan; Schartl, Manfred; Walter, Ronald B

    2015-12-01

    The phenotypic and genetic similarities between Xiphophorus and human melanoma render Xiphophorus a useful animal model for studying the genetic basis of melanoma etiology. In the Xiphophorus model, melanoma has been shown to be inducible by ultraviolet light (UVB) exposure among interspecies hybrids, but not in parental line fish similarly treated. This leads to questions of what genes are responsive to UVB exposure in the skin of the interspecies hybrids, as well as how parental alleles in hybrids may be differentially regulated and the potential roles they may play in induced melanomagenesis. To address these questions, we produced X. maculatus Jp 163 B×X. couchianus (Sp-Couch) F1 hybrid fish, exposed both hybrid and parental fish to UVB, and performed gene expression profiling of the skin using RNA-Seq methodology. We characterized a group of unique UVB-responsive genes in Sp-Couch hybrid including dct, pmela, tyr, tyrp1a, slc2a11b, rab38a, rab27, tspan10, slc45a2, oca2, slc24a5, ptn and mitfa. These genes are associated with melanin production and melanocyte proliferation. They were also up-regulated in Sp-Couch hybrid, indicating that their UVB response is hybridization initiated. In the hybrid, several melanin production and pigmentation related genes, including slc45a2, tspan10, dct, slc2a11b and ptn showed either X. couchianus or X. maculatus allele specific expression. The finding that these genes exhibit allele specific expression regulatory mechanisms in Sp-Couch hybrids, but do not exhibit a corresponding UVB response in either one of the parental fishes, may suggest UVB targets and imply mechanisms regarding the susceptibility of Sp-Couch to induced melanomagenesis. PMID:26254713

  16. Report of a patient with complex composites of hepatitis B virus, allergic asthma and diabetes

    PubMed Central

    Athari, Seyyed Shamsadin; Omidi, Razie

    2014-01-01

    HBV is a non-cytopathic virus and cell mediated immune response against this. Humoral mediated immune response are responsible for allergic diseases. Balance between these two subsets of Th CD4+ cells are result of the immune system response. A 56 year old woman presented with chronic HBV infection, allergic asthma, type 2 diabetes mellitus and high blood pressure and high blood lipid. Patients should be followed for the allergic and autoimmune diseases along with their viral reactivation. PMID:25183147

  17. Salicylic acid derivatives as potential anti asthmatic agents using disease responsive drug delivery system for prophylactic therapy of allergic asthma.

    PubMed

    Raju, Kalidhindi Rama Satyanarayana; Ambhore, Nilesh S; Mulukutla, Shashank; Gupta, Saurabh; Murthy, Vishakantha; Kumar, M N Kiran; Madhunapantula, Subba Rao V; Kuppuswamy, Gowthamarajan; Elango, Kannan

    2016-02-01

    Asthma is a multi-factorial and complicated lung disorder of the immune system which has expanded to a wider ambit unveiling its etiology to be omnipresent at both ends of the spectrum involving basic pharmacology and in-depth immunology. As asthma occurs through triggered activation of various immune cells due to different stimuli, it poses a great challenge to uncover specific targets for therapeutic interventions. Recent pharmacotherapeutic approaches for asthma have been focused on molecular targeting of transcription factors and their signaling pathways; mainly nucleus factor kappa B (NFκB) and its associated pathways which orchestrate the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, GM-CSF), chemokines (RANTES, MIP-1a, eotaxin), adhesion molecules (ICAM-1, VCAM-1) and inflammatory enzymes (cyclooxygenase-2 and iNOS). 5-aminosalicylic acid (5-ASA) and sodium salicylate are known to suppress NFκB activation by inhibiting inhibitor of kappa B kinase (IKκB). In order to target the transcription factor, a suitable carrier system for delivering the drug to the intracellular space is essential. 5-ASA and sodium salicylate loaded liposomes incorporated into PEG-4-acrylate and CCRGGC microgels (a polymer formed by crosslinking of trypsin sensitive peptide and PEG-4-acrylate) could probably suit the needs for developing a disease responsive drug delivery system which will serve as a prophylactic therapy for asthmatic patients. PMID:26643666

  18. Pollen Lipidomics: Lipid Profiling Exposes a Notable Diversity in 22 Allergenic Pollen and Potential Biomarkers of the Allergic Immune Response

    PubMed Central

    Bashir, Mohamed Elfatih H.; Lui, Jan Hsi; Palnivelu, Ravishankar; Naclerio, Robert M.; Preuss, Daphne

    2013-01-01

    lipids vary greatly among allergenic species and contain many molecules that have stimulatory or regulatory effects on immune responses. PMID:23469025

  19. Skin-colour changes i the lizard, Anolis carolinensis, in response to localized electrical stimulation and lesions in the diencephalon.

    PubMed

    Hemer, J H; Salas, M A; LaPointe, J L

    1981-05-01

    A study was made of changes in skin colour in the lizard, Anolis carolinensis, in response to deep electrical stimulation at 0.2 mm intervals throughout the periventricular region of the diencephalon and the anterior brain stem. Double-barrelled glass microelectrodes with tip diameters of 3 microns were used. A 20 microA pulse-train consisting of a 500 Hz signal lasting for 1 s yielded localized responses. Skin darkening occurred only in response to stimulation delivered in the anterior and dorsal region of the diencephalon and skin lightening only in response to stimulation in a small area in the posterior and ventral region of the hypothalamus. Electrical lesions in the latter region resulted in permanent skin darkening. Surgical interruption of the hypothalamo-hypophysial neurosecretory tract did not block skin-colour change in response to dark or light backgrounds. It was concluded that MSH release is under tonic inhibitory control by hypothalamic neurones in Anolis. Both inhibitory and stimulatory neurones can be localized stereotaxically in the diencephalon and neither type corresponds with the neurosecretory neurones of the hypothalamo-hypophysial tract. The functional relationship between the stimulatory neurones and the inhibitory neurones and pars intermedia remains unclear. PMID:7017054

  20. Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow’s Milk Proteins

    PubMed Central

    Ibañez, Andrés E.; Smaldini, Paola; Coria, Lorena M.; Delpino, María V.; Pacífico, Lucila G. G.; Oliveira, Sergio C.; Risso, Gabriela S.; Pasquevich, Karina A.; Fossati, Carlos Alberto; Giambartolomei, Guillermo H.; Docena, Guillermo H.; Cassataro, Juliana

    2013-01-01

    The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow’s Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations. PMID:23861971

  1. Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.

    PubMed Central

    Burns, Fredric J; Uddin, Ahmed N; Wu, Feng; Nádas, Arthur; Rossman, Toby G

    2004-01-01

    The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experiment ended at 182 days. Untreated mice and mice fed only arsenite developed no tumors. In the remaining groups a total of 322 locally invasive squamous carcinomas occurred. The carcinoma yield in mice exposed only to UVR was 2.4 +/- 0.5 cancers/mouse at 182 days. Dietary arsenite markedly enhanced the UVR-induced cancer yield in a pattern consistent with linearity up to a peak of 11.1 +/- 1.0 cancers/mouse at 5.0 mg/L arsenite, representing a peak enhancement ratio of 4.63 +/- 1.05. A decline occurred to 6.8 +/- 0.8 cancers/mouse at 10.0 mg/L arsenite. New cancer rates exhibited a consistent-with-linear dependence on time beginning after initial cancer-free intervals ranging between 88 and 95 days. Epidermal hyperplasia was elevated by arsenite alone and UVR alone and was greater than additive for the combined exposures as were growth rates of the cancers. These results demonstrate the usefulness of a new animal model for studying the carcinogenic action of dietary arsenite on skin exposed to UVR and should contribute to understanding how to make use of animal data for assessment of human cancer risks in tissues exposed to mixtures of carcinogens and cancer-enhancing agents. PMID:15064167

  2. Evidence for humoral effects on the radiation response of rat foot skin.

    PubMed

    Rezvani, M; Ross, G A; Wilkinson, J H; Bywaters, A

    2002-01-01

    The influence of perturbation of the physiologic state of the whole body on the outcome of radiation exposure has been examined in a rat foot model. Irradiation was carried out using 60Co gamma-rays. Moist desquamation was used as an endpoint. Rats were given a priming dose of 2 Gy, 4 Gy or 7 Gy to their whole body except their hind feet (partial body priming dose). After a variable time period both hind feet of these animals were irradiated with graded doses of 60Co gamma-rays. The incidence of moist desquamation in the irradiated feet of these animals was compared with the incidence of moist desquamation in animals that had not received the initial partial body priming dose. It was noticed that the incidence of moist desquamation in the rat foot skin of animals that received 7 Gy partial body priming dose 4 h prior to irradiation of their hind feet was significantly less than moist desquamation in control animals. The ED(50) value of 22.53+/-0.16 Gy for moist desquamation of the foot skin of control animals was significantly lower (p<0.01) than the value of 25.25+/-0.29 Gy obtained for animals that received a partial body priming dose of 7 Gy 4 h prior to irradiation of their hind feet. It was concluded that the response of rat foot skin to radiation was not purely the result of epidermal stem cell kill and that it can be modified by alterations in the overall physiological state of the animal's body brought about by a priming dose to the whole of the animal's body except the hind feet. PMID:11806958

  3. In vivo analysis of THz wave irradiation induced acute inflammatory response in skin by laser-scanning confocal microscopy.

    PubMed

    Hwang, Yoonha; Ahn, Jinhyo; Mun, Jungho; Bae, Sangyoon; Jeong, Young Uk; Vinokurov, Nikolay A; Kim, Pilhan

    2014-05-19

    The recent development of THz sources in a wide range of THz frequencies and power levels has led to greatly increased interest in potential biomedical applications such as cancer and burn wound diagnosis. However, despite its importance in realizing THz wave based applications, our knowledge of how THz wave irradiation can affect a live tissue at the cellular level is very limited. In this study, an acute inflammatory response caused by pulsed THz wave irradiation on the skin of a live mouse was analyzed at the cellular level using intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 μs pulsewidth, 61.4 μJ per pulse, 3Hz repetition), generated using compact FEL, was used to irradiate an anesthetized mouse's ear skin with an average power of 260 mW/cm(2) for 30 minutes using a high-precision focused THz wave irradiation setup. In contrast to in vitro analysis using cultured cells at similar power levels of CW THz wave irradiation, no temperature change at the surface of the ear skin was observed when skin was examined with an IR camera. To monitor any potential inflammatory response, resident neutrophils in the same area of ear skin were repeatedly visualized before and after THz wave irradiation using a custom-built laser-scanning confocal microscopy system optimized for in vivo visualization. While non-irradiated control skin area showed no changes in the number of resident neutrophils, a massive recruitment of newly infiltrated neutrophils was observed in the THz wave irradiated skin area after 6 hours, which suggests an induction of acute inflammatory response by the pulsed THz wave irradiation on the skin via a non-thermal process. PMID:24921268

  4. Optimising a model-based approach to inferring fear learning from skin conductance responses

    PubMed Central

    Staib, Matthias; Castegnetti, Giuseppe; Bach, Dominik R.

    2015-01-01

    Anticipatory sympathetic arousal is often inferred from skin conductance responses (SCR) and used to quantify fear learning. We have previously provided a model-based approach for this inference, based on a quantitative Psychophysiological Model (PsPM) formulated in non-linear dynamic equations. Here we seek to optimise the inversion of this PsPM. Using two independent fear conditioning datasets, we benchmark predictive validity as the sensitivity to separate the likely presence or absence of the unconditioned stimulus. Predictive validity is optimised across both datasets by (a) using a canonical form of the SCR shape (b) filtering the signal with a bi-directional band-pass filter with cut off frequencies 0.0159 and 5 Hz, (c) simultaneously inverting two trials (d) explicitly modelling skin conductance level changes between trials (e) the choice of the inversion algorithm (f) z-scoring estimates of anticipatory sympathetic arousal from each participant across trials. The original model-based method has higher predictive validity than conventional peak-scoring or an alternative model-based method (Ledalab), and benefits from constraining the model, optimised data preconditioning, and post-processing of ensuing parameters. PMID:26291885

  5. Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

    NASA Astrophysics Data System (ADS)

    Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

    2015-09-01

    Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

  6. Leukotriene B(4) mediates sphingosylphosphorylcholine-induced itch-associated responses in mouse skin.

    PubMed

    Andoh, Tsugunobu; Saito, Ayumi; Kuraishi, Yasushi

    2009-12-01

    In atopic dermatitis, the concentration in the skin of sphingosylphosphorylcholine (SPC), which is produced from sphingomyelin by sphingomyelin deacylase, is increased. In the present study, we investigated the itch-eliciting activity of SPC and related substances and the mechanisms of SPC action in mice. An intradermal injection of SPC, but not sphingomyelin and sphingosine, induced scratching, an itch-associated response, which was not suppressed by a deficiency in mast cells or the H(1) histamine receptor antagonist terfenadine. The action of SPC was inhibited by the mu-opioid receptor antagonist naltrexone. SPC action also was inhibited by the 5-lipoxygenase inhibitor zileuton and the leukotriene B(4) antagonist ONO-4057, but not by the cyclooxygenase inhibitor indomethacin. Moreover, SPC action was inhibited by the antiallergic agent azelastine, which suppresses the action and production of leukotriene B(4). Administration of SPC to the skin and to primary cultures of keratinocytes increased leukotriene B(4) production. SPC increased intracellular Ca(2+) ion concentration in primary cultures of dorsal root ganglion neurons and keratinocytes. These results suggest that SPC induces itching through a direct action on primary afferents and leukotriene B(4) production of keratinocytes. Sphingomyelin deacylase and SPC receptors may be previously unreported targets for antipruritic drugs. PMID:19657356

  7. Response of human skin to ultraviolet radiation: dissociation of erythema and metabolic changes following sunscreen protection

    SciTech Connect

    Pearse, A.D.; Marks, R.

    1983-03-01

    After UV irradiation of human skin there is an increase in epidermal and stratum corneum thickness and an increase in the thymidine autoradiographic labeling index. Previously we have demonstrated that persistent exposure to ultraviolet radiation (UVR) alters the distribution and activities of glucose-6-phosphate dehydrogenase (G-6-PDH) and succinic dehydrogenase (SDH) within the epidermis; G-6-PDH activity is increased over the whole epidermis and SDH activity is diminished in the granular cell area but increased in the basal layer. When skin is protected by an efficient sunscreen and irradiated with UVB, there is almost complete inhibition of the erythema normally seen following UVR exposure. In this study we have investigated the cytochemical, cell kinetic, and histometric changes that take place in the epidermis after UVB irradiation, with and without two different types of sunscreen. Some of the histometric and metabolic changes associated with UVB exposure were still evident despite sunscreen protection and the successful blocking of the erythema response. The implications of these findings are discussed together with the use of sunscreens to prevent development of solar damage.

  8. Imaging immune response of skin mast cells in vivo with two-photon microscopy

    NASA Astrophysics Data System (ADS)

    Li, Chunqiang; Pastila, Riikka K.; Lin, Charles P.

    2012-02-01

    Intravital multiphoton microscopy has provided insightful information of the dynamic process of immune cells in vivo. However, the use of exogenous labeling agents limits its applications. There is no method to perform functional imaging of mast cells, a population of innate tissue-resident immune cells. Mast cells are widely recognized as the effector cells in allergy. Recently their roles as immunoregulatory cells in certain innate and adaptive immune responses are being actively investigated. Here we report in vivo mouse skin mast cells imaging with two-photon microscopy using endogenous tryptophan as the fluorophore. We studied the following processes. 1) Mast cells degranulation, the first step in the mast cell activation process in which the granules are released into peripheral tissue to trigger downstream reactions. 2) Mast cell reconstitution, a procedure commonly used to study mast cells functioning by comparing the data from wild type mice, mast cell-deficient mice, and mast-cell deficient mice reconstituted with bone marrow-derived mast cells (BMMCs). Imaging the BMMCs engraftment in tissue reveals the mast cells development and the efficiency of BMMCs reconstitution. We observed the reconstitution process for 6 weeks in the ear skin of mast cell-deficient Kit wsh/ w-sh mice by two-photon imaging. Our finding is the first instance of imaging mast cells in vivo with endogenous contrast.

  9. Optimising a model-based approach to inferring fear learning from skin conductance responses.

    PubMed

    Staib, Matthias; Castegnetti, Giuseppe; Bach, Dominik R

    2015-11-30

    Anticipatory sympathetic arousal is often inferred from skin conductance responses (SCR) and used to quantify fear learning. We have previously provided a model-based approach for this inference, based on a quantitative Psychophysiological Model (PsPM) formulated in non-linear dynamic equations. Here we seek to optimise the inversion of this PsPM. Using two independent fear conditioning datasets, we benchmark predictive validity as the sensitivity to separate the likely presence or absence of the unconditioned stimulus. Predictive validity is optimised across both datasets by (a) using a canonical form of the SCR shape (b) filtering the signal with a bi-directional band-pass filter with cut off frequencies 0.0159 and 5 Hz, (c) simultaneously inverting two trials (d) explicitly modelling skin conductance level changes between trials (e) the choice of the inversion algorithm (f) z-scoring estimates of anticipatory sympathetic arousal from each participant across trials. The original model-based method has higher predictive validity than conventional peak-scoring or an alternative model-based method (Ledalab), and benefits from constraining the model, optimised data preconditioning, and post-processing of ensuing parameters. PMID:26291885

  10. [Genetic study of allergic diseases].

    PubMed

    Zhang, Yuan; Zhang, Luo

    2012-09-01

    Allergic diseases mentioned in this review is regarding to I type allergic inflammation induced by an IgE-mediated reaction, including asthma, allergic rhinitis, atopic dermatitis and food allergy. It is convinced that allergic diseases belong to multiple genes diseases and are controlled by both genetic and environmental factors. Meanwhile there exists gene-gene as well as gene-environment interactions during the development of the disease. The aim of this review is to summarize the toolkit, advance, inherent difficulties and future clinical application prospect in genetic studies of allergic disease. PMID:23214325

  11. Diagnosing Allergic Rhinitis.

    PubMed

    Scadding, Glenis K; Scadding, Guy W

    2016-05-01

    Allergic rhinitis (AR) is the most common immunologic disease in industrialized societies and has a significant impact on quality of life. Most asthmatics also have rhinitis. AR may present with comorbidities, including chronic otitis media with effusion, cough, and pollen-food cross-reactivity. AR may occur in isolation or be part of a mixed rhinitis. PMID:27083100

  12. Religious Allergic Contact Dermatitis.

    PubMed

    Goldenberg, Alina; Matiz, Catalina; Eichenfield, Lawrence F

    2015-01-01

    Henna, derived from a combination of natural leaves and coloring additives, is a common decorative dye traditionally used in many Islamic religious celebrations. Para-phenylenediamine (PPD), a major component of black henna tattoo, is a strong sensitizer and common allergen. We report a case of severe connubial allergic contact dermatitis after black henna heterotransfer in a girl. PMID:25968562

  13. Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment.

    PubMed

    Hosoki, Koa; Aguilera-Aguirre, Leopoldo; Brasier, Allan R; Kurosky, Alexander; Boldogh, Istvan; Sur, Sanjiv

    2016-01-01

    Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate pollen-induced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways. Deletion of Toll-like receptor 4 (TLR4) abolishes CXCL chemokine secretion and neutrophil recruitment induced by a single RWPE challenge and inhibits induction of allergic sensitization and airway inflammation after repeated exposures to RWPE. Forced induction of CXCL chemokine secretion and neutrophil recruitment in mice lacking TLR4 also reconstitutes the ability of multiple challenges of RWPE to induce allergic airway inflammation. Blocking RWPE-induced neutrophil recruitment in wild-type mice by administration of a CXCR2 inhibitor inhibits the ability of repeated exposures to RWPE to stimulate allergic sensitization and airway inflammation. Administration of neutrophils derived from naive donor mice into the airways of Tlr4 knockout recipient mice after each repeated RWPE challenge reconstitutes allergic sensitization and inflammation in these mice. Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation. Inhibiting pollen-induced recruitment of neutrophils, such as by administration of CXCR2 antagonists, may be a novel strategy to prevent initiation of pollen-induced allergic airway inflammation. PMID:26086549

  14. Character of skin on photo-thermal response and its regeneration process using second-harmonic generation microscopy.

    PubMed

    Wu, Shu-lian; Li, Hui; Zhang, Xiao-man; Chen, Wei R; Wang, Yun-Xia

    2014-01-01

    Quantitative characterization of skin collagen on photo-thermal response and its regeneration process is an important but difficult task. In this study, morphology and spectrum characteristics of collagen during photo-thermal response and its light-induced remodeling process were obtained by second-harmonic generation microscope in vivo. The texture feature of collagen orientation index and fractal dimension was extracted by image processing. The aim of this study is to detect the information hidden in skin texture during the process of photo-thermal response and its regeneration. The quantitative relations between injured collagen and texture feature were established for further analysis of the injured characteristics. Our results show that it is feasible to determine the main impacts of phototherapy on the skin. It is important to understand the process of collagen remodeling after photo-thermal injuries from texture feature. PMID:23508280

  15. Cortisol, biochemical, and galvanic skin responses to music stimuli of different preference values by college students in biology and music.

    PubMed

    VanderArk, S D; Ely, D

    1993-08-01

    The purpose of this study was to examine biochemical and galvanic skin responses to music stimuli. Specifically, 30 university biology and 30 music students' plasma levels of norepinephrine and cortisol and their galvanic skin responses were measured before and after listening to two different musical selections, one of which was preferred (liked) by the music students and not preferred (disliked) by the biology students. The music-listening sessions and the controlled silent sessions were done in an anechoic chamber. 30 biology majors and 30 music majors were in the experimental groups; 14 biology and 17 music majors comprised the control group. Analysis indicated that the cortisol levels and galvanic skin responses were significantly higher for the music majors than the biology majors. The data indicate that music majors listen more critically and analytically to music than biology majors, and cortisol levels are associated with this as increases in music majors and decreases in biology majors after the music. PMID:8367245

  16. Recent Patents and Emerging Therapeutics in the Treatment of Allergic Conjunctivitis

    PubMed Central

    Mishra, Gyan P.; Tamboli, Viral; Jwala, Jwala; Mitra, Ashim K.

    2011-01-01

    Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, non-steroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. PMID:21171952

  17. A stress sensor based on Galvanic Skin Response (GSR) controlled by ZigBee.

    PubMed

    Villarejo, María Viqueira; Zapirain, Begoña García; Zorrilla, Amaia Méndez

    2012-01-01

    Sometimes, one needs to control different emotional situations which can lead the person suffering them to dangerous situations, in both the medium and short term. There are studies which indicate that stress increases the risk of cardiac problems. In this study we have designed and built a stress sensor based on Galvanic Skin Response (GSR), and controlled by ZigBee. In order to check the device's performance, we have used 16 adults (eight women and eight men) who completed different tests requiring a certain degree of effort, such as mathematical operations or breathing deeply. On completion, we appreciated that GSR is able to detect the different states of each user with a success rate of 76.56%. In the future, we plan to create an algorithm which is able to differentiate between each state. PMID:22778631

  18. Analysis of skin conductance response during evaluation of preferences for cosmetic products

    PubMed Central

    Ohira, Hideki; Hirao, Naoyasu

    2015-01-01

    We analyzed skin conductance response (SCR) as a psychophysiological index to evaluate affective aspects of consumer preferences for cosmetic products. To examine the test-retest reliability of association between preferences and SCR, we asked 33 female volunteers to complete two experimental sessions approximately 1 year apart. The participants indicated their preferences in a typical paired comparison task by choosing the better option from a combination of two products among four products. We measured anticipatory SCR prior to expressions of the preferences. We found that the mean amplitude of the SCR elicited by the preferred products was significantly larger than that elicited by the non-preferred products. The participants' preferences and corresponding SCR patterns were well preserved at the second session 1 year later. Our results supported cumulating findings that SCR is a useful index of consumer preferences that has future potential, both in laboratory and marketing settings. PMID:25709593

  19. Distinct roles of prostaglandin D2 receptors in chronic skin inflammation.

    PubMed

    Matsushima, Yuki; Satoh, Takahiro; Yamamoto, Yoshihiro; Nakamura, Masataka; Yokozeki, Hiroo

    2011-10-01

    Prostaglandin D2 (PGD2) is a prostanoid implicated in allergic inflammation. However, the roles of PGD2 in immune and allergic responses remain controversial. PGD2 exerts its effect through the CRTH2 and DP receptors. To elucidate functional differences of PGD2 and its receptors in chronic skin inflammation, chronic contact hypersensitivity (chronic CHS) and IgE-mediated chronic allergic skin inflammation (IgE-CAI) were induced in mice deficient in the CRTH2 and/or DP genes. DP (-/-) mice and CRTH2 (-/-)/DP (-/-) mice showed exacerbated chronic CHS, and conversely, CRTH2 (-/-) mice exhibited diminished skin responses. Skin responses correlated with local levels of IL-13, CCL11, and CCL22. These phenotypic changes in chronic CHS of mutant mice were similar to those in acute CHS despite the differences in the cytokine milieus; chronic CHS and acute CHS were mediated by Th2 and Th1/Th17 immunity, respectively. However, in IgE-CAI, DP (-/-) mice showed comparable skin responses to wild-type mice. Alleviation of IgE-CAI was observed in CRTH2 (-/-) mice, and as a consequence, CRTH2 (-/-)/DP (-/-) mice exhibited diminished IgE-CAI compared with wild-type mice. IgE-CAI in mutant mice correlated with local IL-4 and CCL22 production. Consistent with these results, a CRTH2-specific antagonist exerted inhibitory effects in both chronic CHS and IgE-CAI. The present study demonstrates that functional roles of PGD2 and its receptors appear to depend on the nature of the inflammation. Nevertheless, tools targeted against PGD2-CRTH2 signals could offer therapeutic potential for both types of chronic skin inflammation. PMID:21943706

  20. Skin Metabolite, Farnesyl Pyrophosphate, Regulates Epidermal Response to Inflammation, Oxidative Stress, and Migration.

    PubMed

    Pastar, Irena; Stojadinovic, Olivera; Sawaya, Andrew P; Stone, Rivka C; Lindley, Linsey E; Ojeh, Nkemcho; Vukelic, Sasa; Samuels, Herbert H; Tomic-Canic, Marjana

    2016-11-01

    Skin produces cholesterol and a wide array of sterols and non-sterol mevalonate metabolites, including isoprenoid derivative farnesyl pyrophosphate (FPP). To characterize FPP action in epidermis, we generated transcriptional profiles of primary human keratinocytes treated with zaragozic acid (ZGA), a squalene synthase inhibitor that blocks conversion of FPP to squalene resulting in endogenous accumulation of FPP. The elevated levels of intracellular FPP resulted in regulation of epidermal differentiation and adherens junction signaling, insulin growth factor (IGF) signaling, oxidative stress response and interferon (IFN) signaling. Immunosuppressive properties of FPP were evidenced by STAT-1 downregulation and prominent suppression of its nuclear translocation by IFNγ. Furthermore, FPP profoundly downregulated genes involved in epidermal differentiation of keratinocytes in vitro and in human skin ex vivo. Elevated levels of FPP resulted in induction of cytoprotective transcriptional factor Nrf2 and its target genes. We have previously shown that FPP functions as ligand for the glucocorticoid receptor (GR), one of the major regulator of epidermal homeostasis. Comparative microarray analyses show significant but not complete overlap between FPP and glucocorticoid regulated genes, suggesting that FPP may have wider transcriptional impact. This was further supported by co-transfection and chromatin immunoprecipitation experiments where we show that upon binding to GR, FPP recruits β-catenin and, unlike glucocorticoids, recruits co-repressor GRIP1 to suppress keratin 6 gene. These findings have many clinical implications related to epidermal lipid metabolism, response to glucocorticoid therapy as well as pleiotropic effects of cholesterol lowering therapeutics, statins. J. Cell. Physiol. 231: 2452-2463, 2016. © 2016 Wiley Periodicals, Inc. PMID:26916741

  1. Thin-skinned salt tectonics as a response to crustal movements in a recent convergent setting

    NASA Astrophysics Data System (ADS)

    Vendeville, Bruno; Gaullier, Virginie; Deverchere, Jacques; Sage, Françoise

    2014-05-01

    Published data from the seismic survey "MARADJA 1" conducted in August and September 2003 offshore the Algerian coast have imaged the Messinian salt response to tectonic activity within the basement. This helps to understand how the vertical movements of basement blocks have been recorded by thin-skinned salt tectonics. The area is undergoing crustal convergence, as attested by the Boumerdes earthquake (magnitude 6.8), which happened in 2003. The seismic data have revealed the presence of an elevated plateau, forming a 3D promontory restricted to the area offshore Algiers and is absent west and east of that area. The promontory is likely related to the contractional reactivation of the margin, as was recorded by subsalt thrusts mapped by Domzig et al. (2006). The data provided additional information on the deformation of the Messinian mobile evaporite unit and its Plio-Quaternary overburden. Margin-perpendicular profiles show mostly compressional features (anticlines and synclines) that had little or no activity during Messinian times. By contrast, margin-parallel profiles clearly show that extensional, reactive salt diapiric ridges formed early, as early as the time of deposition of the Messinian Upper Unit, as recorded by fan-shaped strata. These ridges have recorded E-W, thin-skinned gravity gliding above the Messinian salt, as a response to the rise of the basement plateau. We tested this hypothesis using analogue models. Indeed, the rise of the plateau generated preferential E-W extension above the salt, rather than N-S, which was prevented by the compressional regional tectonic stresses related to the convergence of the African and European plates.

  2. The effect of body temperature on the hunting response of the middle finger skin temperature.

    PubMed

    Daanen, H A; Van de Linde, F J; Romet, T T; Ducharme, M B

    1997-01-01

    The relationship between body temperature and the hunting response (intermittent supply of warm blood to cold exposed extremities) was quantified for nine subjects by immersing one hand in 8 degree C water while their body was either warm, cool or comfortable. Core and skin temperatures were manipulated by exposing the subjects to different ambient temperatures (30, 22, or 15 degrees C), by adjusting their clothing insulation (moderate, light, or none), and by drinking beverages at different temperatures (43, 37 and 0 degrees C). The middle finger temperature (Tfi) response was recorded, together with ear canal (Tear), rectal (Tre), and mean skin temperature (Tsk). The induced mean Tear changes were -0.34 (0.08) and +0.29 (0.03) degrees C following consumption of the cold and hot beverage, respectively. Tsk ranged from 26.7 to 34.5 degrees C during the tests. In the warm environment after a hot drink, the initial finger temperature (T(fi,base)) was 35.3 (0.4) degrees C, the minimum finger temperature during immersion (T(fi,min)) was 11.3 (0.5) degrees C, and 2.6 (0.4) hunting waves occurred in the 30-min immersion period. In the neutral condition (thermoneutral room and beverage) T(fi,base) was 32.1 (1.0) degrees C, T(fi,min) was 9.6 (0.3) degrees C, and 1.6 (0.2) waves occurred. In the cold environment after a cold drink, these values were 19.3 (0.9) degrees C, 8.7 (0.2) degrees C, and 0.8 (0.2) waves, respectively. A colder body induced a decrease in the magnitude and frequency of the hunting response. The total heat transferred from the hand to the water, as estimated by the area under the middle finger temperature curve, was also dependent upon the induced increase or decrease in Tear and Tsk. We conclude that the characteristics of the hunting temperature response curve of the finger are in part determined by core temperature and Tsk. Both T(fi,min) and the maximal finger temperature during immersion were higher when the core temperature was elevated; Tsk

  3. Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum.

    PubMed

    Smit, Cornelis H; Kies, Christiaan L; McWilliam, Hamish E G; Meeusen, Els N T; Hokke, Cornelis H; van Diepen, Angela

    2016-01-01

    Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted N-glycans with terminal mannose residues, Galβ1-4GlcNAc (LacNAc) and Galβ1-4(Fucα1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAcβ1-4(GlcNAcβ1)n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAcβ1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage- and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection

  4. Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

    PubMed Central

    Smit, Cornelis H.; Kies, Christiaan L.; McWilliam, Hamish E. G.; Meeusen, Els N. T.; Hokke, Cornelis H.

    2015-01-01

    Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted N-glycans with terminal mannose residues, Galβ1-4GlcNAc (LacNAc) and Galβ1-4(Fucα1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAcβ1-4(GlcNAcβ1)n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAcβ1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage- and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection

  5. Differences in allergic inflammatory responses between urban PM2.5 and fine particle derived from desert-dust in murine lungs.

    PubMed

    He, Miao; Ichinose, Takamichi; Kobayashi, Makoto; Arashidani, Keiichi; Yoshida, Seiichi; Nishikawa, Masataka; Takano, Hirohisa; Sun, Guifan; Shibamoto, Takayuki

    2016-04-15

    The biological and chemical natures of materials adsorbed onto fine particulate matter (PM2.5) vary by origin and passage routes. The exacerbating effects of the two samples-urban PM2.5 (U-PM2.5) collected during the hazy weather in a Chinese city and fine particles (ASD-PM2.5) collected during Asian sand dust (ASD) storm event days in Japan-on murine lung eosinophilia were compared to clarify the role of toxic materials in PM2.5. The amounts of β-glucan and mineral components were higher in ASD-PM2.5 than in U-PM2.5. On the other hand, organic chemicals, including polycyclic aromatic hydrocarbons (PAHs), were higher in U-PM2.5 than in ASD-PM2.5. When BALB/c mice were intratracheally instilled with U-PM2.5 and ASD-PM2.5 (total 0.4 mg/mouse) with or without ovalbumin (OVA), various biological effects were observed, including enhancement of eosinophil recruitment induced by OVA in the submucosa of the airway, goblet cell proliferation in the bronchial epithelium, synergic increase of OVA-induced eosinophil-relevant cytokines and a chemokine in bronchoalveolar lavage fluid, and increase of serum OVA-specific IgG1 and IgE. Data demonstrate that U-PM2.5 and ASD-PM2.5 induced allergic inflammatory changes and caused lung pathology. U-PM2.5 and ASD-PM2.5 increased F4/80(+) CD11b(+) cells, indicating that an influx of inflammatory and exudative macrophages in lung tissue had occurred. The ratio of CD206 positive F4/80(+) CD11b(+) cells (M2 macrophages) in lung tissue was higher in the OVA+ASD-PM2.5 treated mice than in the OVA+U-PM2.5 treated mice. These results suggest that the lung eosinophilia exacerbated by both PM2.5 is due to activation of a Th2-associated immune response along with induced M2 macrophages and the exacerbating effect is greater in microbial element (β-glucan)-rich ASD-PM2.5 than in organic chemical-rich U-PM2.5. PMID:26917405

  6. TSLP is differentially regulated by vitamin D3 and cytokines in human skin

    PubMed Central

    Landheer, Janneke; Giovannone, Barbara; Sadekova, Svetlana; Tjabringa, Sandra; Hofstra, Claudia; Dechering, Koen; Bruijnzeel-Koomen, Carla; Chang, Charlie; Ying, Yu; de Waal Malefyt, Rene; Hijnen, DirkJan; Knol, Edward

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases and is highly expressed in keratinocytes in human lesional atopic dermatitis (AD) skin. In nonlesional AD skin TSLP expression can be induced by applying house dust mite allergen onto the skin in the atopy patch test. Several studies have demonstrated that the induction of TSLP expression in mouse skin does not only lead to AD-like inflammation of the skin, but also predisposes to severe inflammation of the airways. In mice, TSLP expression can be induced by application of the 1,25-dihydroxyvitamin D3 (VD3) analogue calcipotriol and results in the development of eczema-like lesions. The objective is to investigate the effect of VD3 (calcitriol) or calcipotriol on TSLP expression in normal human skin and skin from AD patients. Using multiple ex vivo experimental setups, the effects of calci(po)triol on TSLP expression by normal human skin, and skin from AD patients were investigated and compared to effects of calcipotriol on mouse and non-human primates (NHP) skin. No induction of TSLP expression (mRNA or protein) was observed in human keratinocytes, normal human skin, nonlesional AD skin, or NHP skin samples after stimulation with calcipotriol or topical application of calcitriol. The biological activity of calci(po)triol in human skin samples was demonstrated by the increased expression of the VD3-responsive Cyp24a1 gene. TSLP expression was induced by cytokines (IL-4, IL-13, and TNF-α) in skin samples from all three species. In contrast to the findings in human and NHP, a consistent increase in TSLP expression was confirmed in mouse skin biopsies after stimulation with calcipotriol. VD3 failed to induce expression of TSLP in human or monkey skin in contrast to mouse, implicating careful extrapolation of this often-used mouse model to AD patients. PMID:25866638

  7. A Survey of Clinical Features of Allergic Rhinitis in Adults

    PubMed Central

    Frati, Franco; Dell’Albani, Ilaria; Passalacqua, Giovanni; Bonini, Sergio; Rossi, Oliviero; Senna, Gianenrico; Incorvaia, Cristoforo

    2014-01-01

    Background Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18–45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. Conclusions These findings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed. PMID:25366169

  8. Allergic rhinitis and asthma in the athlete.

    PubMed

    Randolph, Christopher C

    2006-01-01

    The pathogenesis, epidemiology, presentation, diagnosis, and management of allergic rhinitis and asthma in the recreational and elite athlete are discussed in this study. There is an increased prevalence of allergic rhinitis and asthma in the elite athlete related to the enhanced ventilation with entrainment of inhalants including allergens as well as irritants such as pollutants in the urban athlete, chlorine in the swimmer, and cold air in the hockey player in the training environment. The history as well as objective exercise challenge and skin-prick tests to inhalants or in vitro allergen testing are essential in conjunction with a comprehensive physical exam to diagnosis of allergic rhinitis and/or asthma in the athlete. This is particularly necessary for the elite or competitive athlete who often has poor insight into the symptoms. Management is with appropriate inhaled steroids and/or leukotriene antagonists for the upper (nasal) and lower airways with avoidance of inhaled allergens and/or appropriate immunotherapy where relevant. The optimal management of the athlete results in minimum medication with minimum adverse side effects and optimal outcome. Proper adherence to antidoping regulations and application for use exemption in competitive athletes is recommended. The athlete should be encouraged to pursue the selected sports activity without limitations. PMID:16724626

  9. Rupatadine in allergic rhinitis and chronic urticaria.

    PubMed

    Mullol, J; Bousquet, J; Bachert, C; Canonica, W G; Gimenez-Arnau, A; Kowalski, M L; Martí-Guadaño, E; Maurer, M; Picado, C; Scadding, G; Van Cauwenberge, P

    2008-04-01

    overall well-being of patients with allergic rhinitis or CIU based on findings from quality of life questionnaires and patient global rating scores in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of histamine H(1)- and PAF-receptors, which has been shown to be an effective and generally well-tolerated treatment for allergic rhinitis and chronic urticaria. It possesses a broader profile of anti-inflammatory properties inhibiting both inflammatory cells and a range of mediators involved in the early- and late-phase inflammatory response, but the clinical relevance of these effects remain to be clarified. PMID:18339040

  10. 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

  11. Topical anaesthesia does not affect cutaneous vasomotor or sudomotor responses in human skin.

    PubMed

    Metzler-Wilson, K; Wilson, T E

    2013-10-01

    (1) The effects of local sensory blockade (topical anaesthesia) on eccrine sweat glands and cutaneous circulation are not well understood. This study aimed to determine whether topical lidocaine/prilocaine alters eccrine sweat gland and cutaneous blood vessel responses. (2) Sweating (capacitance hygrometry) was induced via forearm intradermal microdialysis of five acetylcholine (ACh) doses (1 × 10(-4) to 1 × 10(0) m, 10-fold increments) in control and treated forearm sites in six healthy subjects. Nitric oxide-mediated vasodilatory (sodium nitroprusside) and adrenergic vasoconstrictor (noradrenaline) agonists were iontophoresed in lidocaine/prilocaine-treated and control forearm skin in nine healthy subjects during blood flow assessment (laser Doppler flowmetry, expressed as% from baseline cutaneous vascular conductance; CVC; flux/mean arterial pressure). (3) Non-linear regression curve fitting identified no change in the ED50 of ACh-induced sweating after sensory blockade (-1.42 ± 0.23 logM) compared to control (-1.27 ± 0.23 logM; P > .05) or in Emax (0.43 ± 0.08 with, 0.53 ± 0.16 mg cm(-2) min(-1) without lidocaine/prilocaine; P > .05). Sensory blockade did not alter the vasodilator response to sodium nitroprusside (1280 ± 548% change from baseline CVC with, 1204 ± 247% without lidocaine/prilocaine) or vasoconstrictor response to noradrenaline (-14 ± 4% change from baseline CVC with, -22 ± 14% without lidocaine/prilocaine; P > 0.05). (4) Cutaneous sensory blockade does not appear to alter nitric oxide-mediated vasodilation, adrenergic vasoconstriction, or cholinergic eccrine sweating dose-response sensitivity or responsiveness to maximal dose. Thus, lidocaine/prilocaine treatment should not affect sweat gland function or have blood flow implications for subsequent research protocols or clinical procedures. PMID:23663206

  12. 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. PMID:25000234

  13. Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand.

    PubMed Central

    Macefield, G; Gandevia, S C; Burke, D

    1990-01-01

    1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty-five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty-five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant-voltage positive pulses (0.3-0.8 V, 0.1-0.2 ms, 1-100 Hz) or constant-current biphasic pulses (0.4-13.0 microA, 0.2 ms, 1-100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73%) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88%) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88%) microstimulation evoked sensations of 'flutter-vibration', and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of 'sustained pressure'. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83%) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the

  14. Skin surface lipids of the domestic chicken, and neutral lipid standards as stimuli for the penetration response of Austrobilharzia variglandis cercariae.

    PubMed

    Zibulewsky, J; Fried, B; Bacha, W J

    1982-10-01

    Lipids were extracted from the skin of 2-wk-old domestic chickens using sterile cotton gauze dampened with chloroform:methanol (2:1). Preparative thin-layer chromatography separated the skin lipids into six major fractions: phospholipids, free sterols, free fatty acids, triglycerides, methyl esters, sterol esters. The penetration response of the marine avian schistosome cercaria, Austrobilharzia variglandis, to chicken skin lipid fractions, and to neutral lipid standards, was tested by coating lipids on agar in a Petri dish containing a seawater overlay. All neutral lipids tested produced significantly greater penetration responses than the chloroform control. The phospholipid skin fraction killed cercariae. Lipid from whole chicken skin produced the greatest penetration response, followed by free fatty acids and free sterol skin fractions. Of the standards tested, the whole neutral lipid standard, containing cholesterol, oleic acid, triolein, methyl oleate, and cholesteryl oleate, produced the greatest response, followed by the cholesterol standard and the oleic acid standard. PMID:7131196

  15. 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

  16. [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

  17. Divergent metabolic responses of Apostichopus japonicus suffered from skin ulceration syndrome and pathogen challenge.

    PubMed

    Shao, Yina; Li, Chenghua; Ou, Changrong; Zhang, Peng; Lu, Yali; Su, Xiurong; Li, Ye; Li, Taiwu

    2013-11-13

    Skin ulceration syndrome (SUS) is the main limitation in the development of Apostichopus japonicus culture industries, in which Vibrio splendidus has been well documented as one of the major pathogens. However, the intrinsic mechanisms toward pathogen challenge and disease outbreak remain largely unknown at the metabolic level. In this work, the metabolic responses were investigated in muscles of sea cucumber among natural SUS-diseased and V. splendidus-challenged samples. The pathogen did not induce obvious biological effects in A. japonicus samples after infection for the first 24 h. An enhanced energy storage (or reduced energy demand) and immune responses were observed in V. splendidus-challenged A. japonicus samples at 48 h, as marked by increased glucose and branched chain amino acids, respectively. Afterward, infection of V. splendidus induced significant increases in energy demand in A. japonicus samples at both 72 and 96 h, confirmed by decreased glucose and glycogen, and increased ATP. Surprisingly, high levels of glycogen and glucose and low levels of threonine, alanine, arginine, glutamate, glutamine, taurine and ATP were founded in natural SUS-diseased sea cucumber. Our present results provided essential metabolic information about host-pathogen interaction for sea cucumber, and informed that the metabolic biomarkers induced by V. splendidus were not usable for the prediction of SUS disease in practice. PMID:24127639

  18. Body visual discontinuity affects feeling of ownership and skin conductance responses

    PubMed Central

    Tieri, Gaetano; Tidoni, Emmanuele; Pavone, Enea Francesco; Aglioti, Salvatore Maria

    2015-01-01

    When we look at our hands we are immediately aware that they belong to us and we rarely doubt about the integrity, continuity and sense of ownership of our bodies. Here we explored whether the mere manipulation of the visual appearance of a virtual limb could influence the subjective feeling of ownership and the physiological responses (Skin Conductance Responses, SCRs) associated to a threatening stimulus approaching the virtual hand. Participants observed in first person perspective a virtual body having the right hand-forearm (i) connected by a normal wrist (Full-Limb) or a thin rigid wire connection (Wire) or (ii) disconnected because of a missing wrist (m-Wrist) or a missing wrist plus a plexiglass panel positioned between the hand and the forearm (Plexiglass). While the analysis of subjective ratings revealed that only the observation of natural full connected virtual limb elicited high levels of ownership, high amplitudes of SCRs were found also during observation of the non-natural, rigid wire connection condition. This result suggests that the conscious embodiment of an artificial limb requires a natural looking visual body appearance while implicit reactivity to threat may require physical body continuity, even non-naturally looking, that allows the implementation of protective reactions to threat. PMID:26602036

  19. One night of partial sleep deprivation affects habituation of hypothalamus and skin conductance responses.

    PubMed

    Peters, Anja C; Blechert, Jens; Sämann, Philipp G; Eidner, Ines; Czisch, Michael; Spoormaker, Victor I

    2014-09-15

    Sleep disturbances are prevalent in clinical anxiety, but it remains unclear whether they are cause and/or consequence of this condition. Fear conditioning constitutes a valid laboratory model for the acquisition of normal and pathological anxiety. To explore the relationship between disturbed sleep and anxiety in more detail, the present study evaluated the effect of partial sleep deprivation (SD) on fear conditioning in healthy individuals. The neural correlates of 1) nonassociative learning and physiological processing and 2) associative learning (differential fear conditioning) were addressed. Measurements entailed simultaneous functional MRI, EEG, skin conductance response (SCR), and pulse recordings. Regarding nonassociative learning, partial SD resulted in a generalized failure to habituate during fear conditioning, as evidenced by reduced habituation of SCR and hypothalamus responses to all stimuli. Furthermore, SCR and hypothalamus activity were correlated, supporting their functional relationship. Regarding associative learning, effects of partial SD on the acquisition of conditioned fear were weaker and did not reach statistical significance. The hypothalamus plays an integral role in the regulation of sleep and autonomic arousal. Thus sleep disturbances may play a causal role in the development of normal and possibly pathological fear by increasing the susceptibility of the sympathetic nervous system to stressful experiences. PMID:24920020

  20. Quantification of sympathetic vascular responses in skin by laser Doppler flowmetry.

    PubMed

    Khan, F; Spence, V A; Wilson, S B; Abbot, N C

    1991-05-01

    An improved physiological test of focal sympathetic nervous function using a laser Doppler flowmeter is presented. The test evaluates rapid reflex changes in skin blood flow at the finger tip where there are abundant arteriovenous anastomoses with dense sympathetic innervation. Indirect body heating was employed in all subjects to induce central vasodilation and to obtain stable comparable finger tip blood flows prior to stimulus. The reflex vasoconstriction which occurs following inspiratory gasp and contralateral hand cold challenge was quantified and its reproducibility investigated on three separate occasions in 20 young subjects. The variability in responses both within and between young subjects was small. The test was applied to 10 diabetic patients with autonomic neuropathy and to 10 age-matched control subjects. Vasoconstrictor reflexes were significantly lower in the diabetic group (p less than 0.005) with responses lower than 2 SD from the mean for age-matched controls. In conclusion, the test provides an assessment of focal autonomic damage which can be applied to other regions of the body rich in arteriovenous anastomoses and may have application in clinical studies investigating autonomic activity. PMID:2060997

  1. Instructions and the Orienting Reflex in "Semantic Conditioning" of the Galvanic Skin Response in an Innocuous Situation

    ERIC Educational Resources Information Center

    Pendery, Mary; Maltzman, Irving

    1977-01-01

    Concerns the effects of instructions on classical conditioning of the GSR (galvanic skin response). It demonstrates that verbal conditioning of the GSR can be obtained using an innocuous unconditioned stimulus (UCS). Discusses implications for theories of human classical conditioning. (Editor/RK)

  2. Associations between Language Development and Skin Conductance Responses to Faces and Eye Gaze in Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Stagg, Steven D.; Davis, Robert; Heaton, Pamela

    2013-01-01

    Attention to social stimuli is associated with language development, and arousal is associated with the increased viewing of stimuli. We investigated whether skin conductance responses (SCRs) are associated with language development in autism spectrum disorder (ASD): a population that shows abnormalities in both attention to others and language…

  3. Skin turgor

    MedlinePlus

    Doughy skin; Poor skin turgor; Good skin turgor; Decreased skin turgor ... Call your health care provider if: Poor skin turgor occurs with vomiting, diarrhea, or fever. The skin is very slow to return to normal, or the skin "tents" up ...

  4. 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.

  5. Bilastine: in allergic rhinitis and urticaria.

    PubMed

    Carter, Natalie J

    2012-06-18

    Bilastine is an orally administered, second-generation antihistamine used in the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria. In two well designed phase III trials, 14 days' treatment with bilastine was associated with a significantly lower area under the effect curve (AUEC) for the reflective total symptom score (TSS) than placebo in patients with symptomatic seasonal allergic rhinitis. Additionally, reflective nasal symptom scores were significantly lower in bilastine than placebo recipients in patients with a history of seasonal allergic rhinitis who were challenged with grass pollen allergen in a single-centre, phase II study. Neither bilastine nor cetirizine was effective in the treatment of perennial allergic rhinitis with regard to the mean AUEC for reflective TSS in another well designed phase III trial. However, results may have been altered by differences in some baseline characteristics and placebo responses between study countries. In another well designed phase III trial, compared with placebo, bilastine was associated with a significantly greater change from baseline to day 28 in the mean reflective daily urticaria symptom score in patients with chronic urticaria. There were no significant differences in primary endpoint results between bilastine and any of the active comparators used in these trials (i.e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials. PMID:22686617

  6. Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

    PubMed Central

    De Benedetto, Anna; Yoshida, Takeshi; Fridy, Sade; Park, Joo-Eun S.; Kuo, I.-Hsin; Beck, Lisa A.

    2015-01-01

    Atopic Dermatitis (AD), the most common chronic inflammatory skin disease, is characterized by an overactive immune response to a host of environmental allergens and dry, itchy skin. Over the past decade important discoveries have demonstrated that AD develops in part from genetic and/or acquired defects in the skin barrier. Histamine is an aminergic neurotransmitter involved in physiologic and pathologic processes such as pruritus, inflammation, and vascular leak. Enhanced histamine release has been observed in the skin of patients with AD and antihistamines are often prescribed for their sedating and anti-itch properties. Recent evidence suggests that histamine also inhibits the terminal differentiation of keratinocytes and impairs the skin barrier, raising the question whether histamine might play a role in AD barrier impairment. This, coupled with the notion that histamine’s effects mediated through the recently identified histamine receptor H4R, may be important in allergic inflammation, has renewed interest in this mediator in allergic diseases. In this paper we summarize the current knowledge on histamine and histamine receptor antagonists in AD and skin barrier function. PMID:26239353

  7. Power source effects of soft plasma jet and the differential response of skin cancer and normal cells

    NASA Astrophysics Data System (ADS)

    Taylor, Nathaniel; Dobrynin, Danil; Fridman, Alexander; Choi, Eun Ha

    2014-10-01

    The effects of pulsed power direct current energy sources were compared using an indirect discharge plasma jet applied to treat cancerous and normal skin cells. Two power supplies with different voltage and current profiles were compared and optimized through the measurement of physical parameters and evaluated through the treatment of skin cells using an atmospheric pressure nitrogen gas plasma jet. Plasma density and temperature, power output, gas output temperature, and reactive species production were measured. Cell morphology, viability, and ROS generation were investigated using staining. A differential response has been shown between the normal and cancerous cell lines. The cancer cells viability reduced while normal cells did not over the same treatment time.

  8. The Lancet Weight Determines Wheal Diameter in Response to Skin Prick Testing with Histamine

    PubMed Central

    Andersen, Hjalte H.; Elberling, Jesper; Arendt-Nielsen, Lars

    2016-01-01

    Background Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in suboptimal diagnosis of sensitization. Objective Although not previously assessed qualitatively, lancet weight is hypothesized to be important when performing SPT to minimize the frequency of false positives, false negatives, and unwanted discomfort. Methods Accurate weight-controlled SPT was performed on the volar forearms and backs of 20 healthy subjects. Four predetermined lancet weights were applied (25 g, 85 g, 135 g and 265 g) using two positive control histamine solutions (1 mg/mL and 10 mg/mL) and one negative control (saline). A total of 400 SPTs were conducted. The outcome parameters were: wheal size, neurogenic inflammation (measured by superficial blood perfusion), frequency of bleeding, and the lancet provoked pain response. Results The mean wheal diameter increased significantly as higher weights were applied to the SPT lancet, e.g. from 3.2 ± 0.28 mm at 25 g to 5.4 ± 1.7 mm at 265 g (p<0.01). Similarly, the frequency of bleeding, the provoked pain, and the neurogenic inflammatory response increased significantly. At 265 g saline evoked two wheal responses (/160 pricks) below 3 mm. Conclusion and clinical relevance The applied weight of the lancet during the SPT-procedure is an important factor. Higher lancet weights precipitate significantly larger wheal reactions with potential diagnostic implications. This warrants additional research of the optimal lancet weight in relation to SPT-guidelines to improve the specificity and sensitivity of the procedure. PMID:27213613

  9. Peptide Reactivity of Isothiocyanates - Implications for Skin Allergy.

    PubMed

    Karlsson, Isabella; Samuelsson, Kristin; Ponting, David J; Törnqvist, Margareta; Ilag, Leopold L; Nilsson, Ulrika

    2016-01-01

    Skin allergy is a chronic condition that affects about 20% of the population of the western world. This disease is caused by small reactive compounds, haptens, able to penetrate into the epidermis and modify endogenous proteins, thereby triggering an immunogenic reaction. Phenyl isothiocyanate (PITC) and ethyl isothiocyanate (EITC) have been suggested to be responsible for allergic skin reactions to chloroprene rubber, the main constituent of wetsuits, orthopedic braces, and many types of sports gear. In the present work we have studied the reactivity of the isothiocyanates PITC, EITC, and tetramethylrhodamine-6-isothiocyanate (6-TRITC) toward peptides under aqueous conditions at physiological pH to gain information about the types of immunogenic complexes these compounds may form in the skin. We found that all three compounds reacted quickly with cysteine moieties. For PITC and 6-TRITC the cysteine adducts decomposed over time, while stable adducts with lysine were formed. These experimental findings were verified by DFT calculations. Our results may suggest that the latter are responsible for allergic reactions to isothiocyanates. The initial adduct formation with cysteine residues may still be of great importance as it prevents hydrolysis and facilitates the transport of isothiocyanates into epidermis where they can form stable immunogenic complexes with lysine-containing proteins. PMID:26883070

  10. Peptide Reactivity of Isothiocyanates – Implications for Skin Allergy

    PubMed Central

    Karlsson, Isabella; Samuelsson, Kristin; Ponting, David J.; Törnqvist, Margareta; Ilag, Leopold L.; Nilsson, Ulrika

    2016-01-01

    Skin allergy is a chronic condition that affects about 20% of the population of the western world. This disease is caused by small reactive compounds, haptens, able to penetrate into the epidermis and modify endogenous proteins, thereby triggering an immunogenic reaction. Phenyl isothiocyanate (PITC) and ethyl isothiocyanate (EITC) have been suggested to be responsible for allergic skin reactions to chloroprene rubber, the main constituent of wetsuits, orthopedic braces, and many types of sports gear. In the present work we have studied the reactivity of the isothiocyanates PITC, EITC, and tetramethylrhodamine-6-isothiocyanate (6-TRITC) toward peptides under aqueous conditions at physiological pH to gain information about the types of immunogenic complexes these compounds may form in the skin. We found that all three compounds reacted quickly with cysteine moieties. For PITC and 6-TRITC the cysteine adducts decomposed over time, while stable adducts with lysine were formed. These experimental findings were verified by DFT calculations. Our results may suggest that the latter are responsible for allergic reactions to isothiocyanates. The initial adduct formation with cysteine residues may still be of great importance as it prevents hydrolysis and facilitates the transport of isothiocyanates into epidermis where they can form stable immunogenic complexes with lysine-containing proteins. PMID:26883070

  11. DOSE-RESPONSE FOR UV-INDUCED IMMUNE SUPPRESSION IN PEOPLE OF COLOR: DIFFERENCES BASED ON ERYTHEMAL REACTIVITY RATHER THAN SKIN PIGMENTATION

    EPA Science Inventory

    Ultraviolet radiation (UVR) is known to suppress immune responses in human subjects. The purpose of this study was to develop dose responses across a broad range of skin pigmentation in order to facilitate risk assessment. UVR was administered using FS 20 bulbs. Skin pigmentation...

  12. ATP in human skin elicits a dose-related pain response which is potentiated under conditions of hyperalgesia.

    PubMed

    Hamilton, S G; Warburton, J; Bhattacharjee, A; Ward, J; McMahon, S B

    2000-06-01

    minimal erythymic dose) resulted in double the pain rating of normal skin, increasing from 15.3 +/- 4.1 to 32.7 +/- 4.1. The pain response to saline was not significantly altered after UV irradiation at any time-point studied. We conclude that ATP produces pain by activating capsaicin-sensitive nociceptive afferents when applied to skin. The possibility that ATP activates nociceptors indirectly via its degradation products cannot be ruled out. The effects of ATP are dose-dependent and responses desensitize only slowly. In inflammatory conditions, ATP may be a potent activator of nociceptors and an endogenous mediator of pain. PMID:10825361

  13. Skin physiology and textiles - consideration of basic interactions.

    PubMed

    Wollina, U; Abdel-Naser, M B; Verma, S

    2006-01-01

    The skin exerts a number of essential protective functions ensuring homeostasis of the whole body. In the present review barrier function of the skin, thermoregulation, antimicrobial defence and the skin-associated immune system are discussed. Barrier function is provided by the dynamic stratum corneum structure composed of lipids and corneocytes. The stratum corneum is a conditio sine qua non for terrestrial life. Impairment of barrier function can be due to injury and inflammatory skin diseases. Textiles, in particular clothing, interact with skin functions in a dynamic pattern. Mechanical properties like roughness of fabric surface are responsible for non-specific skin reactions like wool intolerance or keratosis follicularis. Thermoregulation, which is mediated by local blood flow and evaporation of sweat, is an important subject for textile-skin interactions. There are age-, gender- and activity-related differences in thermoregulation of skin that should be considered for the development of specifically designed fabrics. The skin is an important immune organ with non-specific and specific activities. Antimicrobial textiles may interfere with non-specific defence mechanisms like antimicrobial peptides of skin or the resident microflora. The use of antibacterial compounds like silver, copper or triclosan is a matter of debate despite their use for a very long period. Macromolecules with antimicrobial activity like chitosan that can be incorporated into textiles or inert material like carbon fibres or activated charcoal seem to be promising agents. Interaction of textiles with the specific immune system of skin is a rare event but may lead to allergic contact dermatitis. Electronic textiles and other smart textiles offer new areas of usage in health care and risk management but bear their own risks for allergies. PMID:16766877

  14. Immunosuppression of the trimellitic anhydride-induced th2 response by novel nonanatural products mixture in mice.

    PubMed

    Bae, Min-Jung; Shin, Hee Soon; Shon, Dong-Hwa

    2013-01-01

    Many natural dietary products prevent or cure allergic inflammation; however, the ability of mixtures of these natural medicinals to suppress allergic skin inflammation is unknown. We examined the inhibitory effects of nonanatural products mixture (NPM-9), which provides immunoregulatory activation, on Th2-mediated skin allergic inflammation. Oral administration of NPM-9 in mice reduced ear thickness and specific IgE production in trimellitic anhydride- (TMA-)induced contact hypersensitivity (CHS). NPM-9 also suppressed IL-4 and IL-1β production in splenocytes but prevented only TMA-induced IL-1β production in inflamed ears. To characterize the mechanism of this effect, we examined NPM-9 immunosuppression on an OVA-induced Th2 allergic state. Oral administration of NPM-9 inhibited Th2-mediated serum IgE overproduction. NPM-9 also downregulated the polarized Th2 response, whereas it upregulated Th1 response in splenocytes. These data suggest that NPM-9 may be a useful therapeutic agent for allergic inflammatory diseases through its suppression of the Th2-mediated allergic response. PMID:24348718

  15. The Seed Biotinylated Protein of Soybean (Glycine max): A Boiling-Resistant New Allergen (Gly m 7) with the Capacity To Induce IgE-Mediated Allergic Responses.

    PubMed

    Riascos, John J; Weissinger, Sandra M; Weissinger, Arthur K; Kulis, Michael; Burks, A Wesley; Pons, Laurent

    2016-05-18

    Soybean is a common allergenic food; thus, a comprehensive characterization of all the proteins that cause allergy is crucial to the development of effective diagnostic and immunotherapeutic strategies. A cDNA library was constructed from seven stages of developing soybean seeds to investigate candidate allergens. We searched the library for cDNAs encoding a seed-specific biotinylated protein (SBP) based on its allergenicity in boiled lentils. A full-length cDNA clone was retrieved and expressed as a 75.6-kDa His-tagged recombinant protein (rSBP) in Escherichia coli. Western immunoblotting of boiled bacterial extracts demonstrated specific IgE binding to rSBP, which was further purified by metal affinity and anion exchange chromatographies. Of the 23 allergic sera screened by ELISA, 12 contained IgEs specific to the purified rSBP. Circular dichroism spectroscopy revealed a predominantly unordered structure consistent with SBP's heat stability. The natural homologues (nSBP) were the main proteins isolated from soybean and peanut embryos after streptavidin affinity purification, yet they remained low-abundance proteins in the seed as confirmed by LC-MS/MS. Using capture ELISAs, the soybean and peanut nSBPs were bound by IgEs in 78 and 87% of the allergic sera tested. The soybean nSBP was purified to homogeneity and treatments with different denaturing agents before immunoblotting highlighted the diversity of its IgE epitopes. In vitro activation of basophils was assessed by flow cytometry in a cohort of peanut-allergic children sensitized to soybean. Stronger and more frequent (38%) activations were induced by nSBP-soy compared to the major soybean allergen, Gly m 5. SBPs may represent a novel class of biologically active legume allergens with the structural resilience to withstand many food-manufacturing processes. PMID:27108990

  16. DOSE-RESPONSE STUDIES OF SODIUM ARSENITE IN THE SKIN OF K6/ODC TRANSGENIC MOUSE

    EPA Science Inventory

    It has previously been observed that chronic exposure to inorganic arsenic and/or its metabolites increase(s) tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, gene expression profiles w...

  17. A novel arctigenin-containing latex glove prevents latex allergy by inhibiting type I/IV allergic reactions.

    PubMed

    Wang, Yong-Xin; Xue, Dan-Ting; Liu, Meng; Zhou, Zheng-Min; Shang, Jing

    2016-03-01

    The present study aimed at developing a natural compound with anti-allergic effect and stability under latex glove manufacturing conditions and investigating whether its anti-allergic effect is maintained after its addition into the latex. The effects of nine natural compounds on growth of the RBL-2H3 cells and mouse primary spleen lymphocytes were determined using MTT assay. The compounds included glycyrrhizin, osthole, tetrandrine, tea polyphenol, catechin, arctigenin, oleanolic acid, baicalin and oxymatrine. An ELISA assay was used for the in vitro anti-type I/IV allergy screening; in this process β-hexosaminidase, histamine, and IL-4 released from RBL-2H3 cell lines and IFN-γ and IL-2 released from mouse primary spleen lymphocytes were taken as screening indices. The physical stability of eight natural compounds and the dissolubility of arctigenin, selected based on the in vitro pharnacodynamaic screening and the stability evaluation, were detected by HPLC. The in vivo pharmacodynamic confirmation of arctigenin and final latex product was evaluated with a passive cutaneous anaphylaxis (PCA) model and an allergen-specific skin response model. Nine natural compounds showed minor growth inhibition on RBL-2H3 cells and mouse primary spleen lymphocytes. Baicalin and arctigenin had the best anti-type I and IV allergic effects among the natural compounds based on the in vitro pharmacodynamic screening. Arctigenin and catechin had the best physical stability under different manufacturing conditions. Arctigenin was the selected for further evaluation and proven to have anti-type I and IV allergic effects in vivo in a dose-dependent manner. The final product of the arctigenin-containing latex glove had anti-type I and IV allergic effects in vivo which were mainly attributed to arctigenin as proved from the dissolubility results. Arctigenin showed anti-type I and IV allergic effects in vitro and in vivo, with a good stability under latex glove manufacturing conditions

  18. Epidermal and dermal changes in response to various skin rejuvenation methods.

    PubMed

    Helbig, D; Simon, J C; Paasch, U

    2010-12-01

    During the last years, a number of new devices have been developed to improve the dermal and epidermal signs of photo- and chronological skin ageing. There are well-established ablative and non-ablative skin resurfacing options using different lasers and light sources, but side effects have been observed frequently. A recently developed photorejuvenation method using non-thermal stimulation of skin cells with low energy and narrow band light has been termed photomodulation. Light emitting diodes are the ideal source of this kind of light that stimulate mitochondrial cell organelles leading to up-regulation of cytochrome electron transport pathway leading to mitochondrial DNA gene modulation. This paper reviews the most current knowledge of intrinsic and extrinsic changes of ageing and summarizes different systems for skin rejuvenation with focus on non-thermal non-ablative skin rejuvenation modalities. PMID:20572891

  19. Skin Barrier Disruption - A Requirement for Allergen Sensitization?

    PubMed Central

    De Benedetto, Anna; Kubo, Akiharu; Beck, Lisa A.

    2011-01-01

    For at least half a century, noninvasive techniques have been available to quantify skin barrier function, and these have shown that a number of human skin conditions and disorders are associated with defects in skin permeability. In the last decade, several genes responsible for skin barrier defects observed in both monogenetic and complex, polygenic disorders have been elucidated and functionally characterized. This has led to an explosion of work in the last six years that has identified pathways connecting epidermal barrier disruption and antigen uptake as well as the quality and/or magnitude of the antigen-specific adaptive immune response. This review will introduce the notion that diseases arise from the dynamic crosstalk that occurs between the skin barrier and immune system using atopic dermatitis or eczema as the disease prototype. Nevertheless, the concepts put forth are highly relevant to a number of antigen-driven disorders for which skin barrier is at least transiently compromised such as psoriasis, allergic contact dermatitis and blistering disorders. PMID:22217737

  20. [The gene or genes of allergic asthma?].

    PubMed

    Demoly, P; Bousquet, J; Godard, P; Michel, F B

    1993-05-15