ILs-3, 6 and 11 increase, but ILs-10 and 24 decrease stemness of human prostate cancer cells in vitro

PubMed Central

Yu, Dandan; Zhong, Yali; Li, Xiaoran; Li, Yaqing; Li, Xiaoli; Cao, Jing; Fan, Huijie; Yuan, Yuan; Ji, Zhenyu; Qiao, Baoping; Wen, Jian-Guo; Zhang, Mingzhi; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

2015-01-01

Cancer stem cells (CSCs) are associated with cancer recurrence and metastasis. Prostate cancer cells often metastasize to the bone with a complex microenvironment of cytokines favoring cell survival. In this study, the cell stemness influence of a group of interleukins including IL-3, 6, 10, 11 and 24 on human prostate cancer cell lines LNCaP and PC-3 was explored in vitro. Sulforhodamine B(SRB) and 5-ethynyl-2′-deoxyuridine (EdU) assays were applied to examine the effect on cell proliferation, and wound healing and transwell assays were used for migration and invasion studies, in addition to colony formation, Western blotting and flowcytometry for the expression of stemness factors and chemotherapy sensitivity. We observed that ILs-3, 6 and 11 stimulated while ILs-10 and 24 inhibited the growth, invasion and migration of both cell lines. Interestingly, ILs-3, 6 and 11 significantly promoted colony formation and increased the expression of SOX2, CD44 and ABCG2 in both prostate cancer cell lines. However, ILs-10 and 24 showed the opposite effect on the expression of these factors. In line with the above findings, treatment with either IL-3 or IL-6 or IL-11 decreased the chemosensitivity to docetaxel while treatment with either IL-10 or IL-24 increased the sensitivity of docetaxel chemotherapy. In conclusion, our results suggest that ILs-3, 6 and 11 function as tumor promoters while ILs-10 and 24 function as tumor suppressors in the prostate cancer cell lines PC-3 and LNCaP in vitro, and such differences may attribute to their different effect on the stemness of PCa cells. PMID:26528857

Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR-2721, rhIL-11 and rhG-CSF on radiation-injured mice

PubMed Central

Jiang, Shuqi; Shen, Xianrong; Liu, Yuming; He, Ying; Jiang, Dingwen; Chen, Wei

2015-01-01

This study investigated the radioprotective effect of Sipunculus nudus L. polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided into seven groups: the control group, the model group and five administration groups. All groups, except the control group, were exposed to a 5 Gy 60Co γ-ray beam. Blood parameters [including white blood cell (WBC), red blood cell (RBC) and platelet counts and hemoglobin level] were assessed three days before irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen, thymus and testicular indices, DNA contents of bone marrow cells, bone marrow nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and estradiol levels in the serum were assessed on the 14th day after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and platelet counts and hemoglobin levels in irradiated mice, and synergistic promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and sperm counts in irradiated mice. The synergistic administration increased the serum SOD activities and serum testosterone content of irradiated mice, but synergy decreased the content of serum MDA and estradiol in irradiated mice. These results suggest that the combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF should increase the efficacy of these drugs for acute radiation sickness, protect immunity, hematopoiesis and the reproductive organs of irradiated-damaged mice, and improve oxidation resistance in the body. PMID:25852150

Emerging roles for IL-11 signaling in cancer development and progression: Focus on breast cancer.

PubMed

Johnstone, Cameron N; Chand, Ashwini; Putoczki, Tracy L; Ernst, Matthias

2015-10-01

Interleukin (IL)-11 is a member of the IL-6 family of cytokines that is defined by the shared use of the GP130 signal transducing receptor subunit. In addition of its long recognized activities as a hemopoietic growth factor, IL-11 has an emerging role in epithelial cancer biology. Through the activation of the GP130-Janus kinase signaling cascade and associated transcription factor STAT3, IL-11 can confer many of the tumor intrinsic 'hallmark' capabilities to neoplastic cells, if they express the ligand-specific IL-11Rα receptor subunit. Accordingly, IL-11 signaling has recently been identified as a rate-limiting step for the growth tumors arising from the mucosa of the gastrointestinal tract. However, there is less appreciation for a potential role of IL-11 to support breast cancer progression, apart from its well documented capacity to facilitate bone metastasis. Here we review evidence that IL-11 expression in breast cancer correlates with poor disease outcome and discuss some of the molecular mechanisms that are likely to underpin these observations. These include the capacity of IL-11 to stimulate survival and proliferation of cancer cells alongside angiogenesis of the primary tumor and of metastatic progenies at distant organs. We review current strategies to interfere with IL-11 signaling and advocate that inhibition of IL-11 signaling may represent an emerging therapeutic opportunity for numerous cancers. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

MAPK regulation of IL-4/IL-13 receptors contributes to the synergistic increase in CCL11/eotaxin-1 in response to TGF-β1 and IL-13 in human airway fibroblasts.

PubMed

Zhou, Xiuxia; Hu, Haizhen; Balzar, Silvana; Trudeau, John B; Wenzel, Sally E

2012-06-15

CCL11/eotaxin-1 is a potent eosinophilic CC chemokine expressed by primary human fibroblasts. The combination of TGF-β1 and IL-13 synergistically increases CCL11 expression, but the mechanisms behind the synergy are unclear. To address this, human airway fibroblast cultures from normal and asthmatic subjects were exposed to IL-13 alone or TGF-β1 plus IL-13. Transcriptional (nuclear run-on) and posttranscriptional (mRNA stability) assays confirmed that transcriptional regulation is critical for synergistic expression of CCL11. TGF-β1 plus IL-13 synergistically increased STAT-6 phosphorylation, nuclear translocation, and binding to the CCL11 promoter as compared with IL-13 alone. STAT-6 small interfering RNA significantly knocked down both STAT-6 mRNA expression and phosphorylation and inhibited CCL11 mRNA and protein expression. Regulation of the IL-4Rα complex by TGF-β1 augmented IL-13 signaling by dampening IL-13Rα2 expression, overcoming IL-13's autoregulation of its pathway and enhancing the expression of CCL11. Our data suggest that TGF-β1 induced activation of the MEK/ERK pathway reduces IL-13Rα2 expression induced by IL-13. Thus, TGF-β1, a pleiotropic cytokine upregulated in asthmatic airways, can augment eosinophilic inflammation by interfering with IL-13's negative feedback autoregulatory loop under MEK/ERK-dependent conditions.

IL-11, IL-1α, IL-6, and TNF-α are induced by solar radiation in vitro and may be involved in facial subcutaneous fat loss in vivo.

PubMed

Li, Wen-Hwa; Pappas, Apostolos; Zhang, Li; Ruvolo, Eduardo; Cavender, Druie

2013-07-01

The loss of subcutaneous (sc) fat is associated with aging. Inflammatory cytokines, such as interleukin-1 α (IL-1α), interleukin-11 (IL-11) and tumor necrosis factor-α (TNF-α), are known to inhibit the differentiation of preadipocytes. This study investigated the potential role of inflammatory cytokines in solar-radiation-induced facial fat loss. Cultured fibroblasts, keratinocytes, and skin equivalents were exposed to various doses of radiation from a solar simulator. Inflammatory cytokines' mRNA production and protein secretion were examined by qRT-PCR and ELISA, respectively. In some experiments, epidermal-dermal equivalents were pretreated topically with a broad-spectrum sunscreen prior to solar simulated radiation (SSR). Human facial preadipocytes treated with recombinant IL-11 or with conditioned media from solar-irradiated equivalents were evaluated for the level of adipocyte differentiation by image analyses, Oil red O staining, and the expression of adipocyte differentiation markers. IL-11, IL-1α, IL-6, and TNF-α protein secretion were induced from epidermal-dermal equivalents by exposure to SSR. A sunscreen prevented SSR-induced inflammatory cytokines production from such equivalents. Exposure of facial preadipocytes to conditioned medium from solar-irradiated epidermal-dermal equivalents inhibited their differentiation into mature adipocytes. Consequently, conditioned medium from sunscreen-pretreated, solar-irradiated equivalents did not inhibit differentiation of preadipocytes. A cocktail of neutralizing antibodies to IL-11, IL-1α, IL-6 and TNF-α significantly reduced the SSR-induced inhibition of preadipocyte differentiation. These results support the hypothesis that SSR-induced inflammatory cytokine may be involved in the photoaging-induced loss of facial subcutaneous fat. Inhibition of this process, e.g. by sunscreens, might slow or prevent photoaging-induced changes in facial contouring. Copyright © 2013 Japanese Society for Investigative

Inactivation of IL11 Signaling Causes Craniosynostosis, Delayed Tooth Eruption, and Supernumerary Teeth

PubMed Central

Nieminen, Pekka; Morgan, Neil V.; Fenwick, Aimée L.; Parmanen, Satu; Veistinen, Lotta; Mikkola, Marja L.; van der Spek, Peter J.; Giraud, Andrew; Judd, Louise; Arte, Sirpa; Brueton, Louise A.; Wall, Steven A.; Mathijssen, Irene M.J.; Maher, Eamonn R.; Wilkie, Andrew O.M.; Kreiborg, Sven; Thesleff, Irma

2011-01-01

Craniosynostosis and supernumerary teeth most often occur as isolated developmental anomalies, but they are also separately manifested in several malformation syndromes. Here, we describe a human syndrome featuring craniosynostosis, maxillary hypoplasia, delayed tooth eruption, and supernumerary teeth. We performed homozygosity mapping in three unrelated consanguineous Pakistani families and localized the syndrome to a region in chromosome 9. Mutational analysis of candidate genes in the region revealed that all affected children harbored homozygous missense mutations (c.662C>G [p.Pro221Arg], c.734C>G [p.Ser245Cys], or c.886C>T [p.Arg296Trp]) in IL11RA (encoding interleukin 11 receptor, alpha) on chromosome 9p13.3. In addition, a homozygous nonsense mutation, c.475C>T (p.Gln159X), and a homozygous duplication, c.916_924dup (p.Thr306_Ser308dup), were observed in two north European families. In cell-transfection experiments, the p.Arg296Trp mutation rendered the receptor unable to mediate the IL11 signal, indicating that the mutation causes loss of IL11RA function. We also observed disturbed cranial growth and suture activity in the Il11ra null mutant mice, in which reduced size and remodeling of limb bones has been previously described. We conclude that IL11 signaling is essential for the normal development of craniofacial bones and teeth and that its function is to restrict suture fusion and tooth number. The results open up the possibility of modulation of IL11 signaling for the treatment of craniosynostosis. PMID:21741611

Association of IL-12p70 and IL-6:IL-10 ratio with autism-related behaviors in 22q11.2 deletion syndrome: a preliminary report.

PubMed

Ross, Heather E; Guo, Ying; Coleman, Karlene; Ousley, Opal; Miller, Andrew H

2013-07-01

22q11.2 deletion syndrome (22q11DS) is a genetic disorder that conveys a significant risk for the development of social behavior disorders, including autism and schizophrenia. Also known as DiGeorge syndrome, 22q11DS is the second most common genetic disorder and is characterized by an elevated risk for immune dysfunction, up to 77% of individuals have an identifiable immune deficiency. We hypothesize that this immune dysfunction could contribute to the elevated risk of impaired social behavior seen in 22q11DS. The current study begins to elucidate these immune deficits and link them with the behavioral alterations associated with the disorder. Serum concentrations of a series of cytokines were examined, using a multiplex immunoassay, in sixteen individuals with 22q11DS and screened for autism-related behavior using the Autism Diagnostic Interview-Revised (ADI-R). This preliminary study examined correlations between specific immune proteins and each of the ADI-R algorithm scores (social, communication, and repetitive behavior). The inflammatory cytokine IL-1β, as well as the ratio between the inflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10, were correlated with social scores (r=0.851, p=0.004; r=0.580, p=0.018). In addition, the inflammatory cytokines interferon gamma and IL-12p70 were correlated with repetitive behaviors (r=0.795, p=0.033; r=0.774, p=0.002). Interestingly, IL-12 has been reported to be increased in autistic children. These data show a positive association between severity of autism-related behaviors and level of serum concentrations of inflammatory cytokines in individuals with 22q11DS, providing a basis for further inquiry. Copyright © 2013 Elsevier Inc. All rights reserved.

Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon-like craniosynostosis

PubMed Central

Keupp, Katharina; Li, Yun; Vargel, Ibrahim; Hoischen, Alexander; Richardson, Rebecca; Neveling, Kornelia; Alanay, Yasemin; Uz, Elif; Elcioğlu, Nursel; Rachwalski, Martin; Kamaci, Soner; Tunçbilek, Gökhan; Akin, Burcu; Grötzinger, Joachim; Konas, Ersoy; Mavili, Emin; Müller-Newen, Gerhard; Collmann, Hartmut; Roscioli, Tony; Buckley, Michael F; Yigit, Gökhan; Gilissen, Christian; Kress, Wolfram; Veltman, Joris; Hammerschmidt, Matthias; Akarsu, Nurten A; Wollnik, Bernd

2013-01-01

We have characterized a novel autosomal recessive Crouzon-like craniosynostosis syndrome in a 12-affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next-generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice-site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon-like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11-mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon-like craniosynostosis. PMID:24498618

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Zhong-Ze; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showedmore » that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.« less

U.S. EPA, Pesticide Product Label, SCOTTS "ALL-OUT" SPOT WEEDER, 03/15/1968

EPA Pesticide Factsheets

2011-04-14

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Where to Find It. Information Resource Centers, ’A Quick Reference Booklet’,

DTIC Science & Technology

1983-09-01

BROWN SEP 83 UNCLASSIFIED F,’G 5 /2 N EEmhohmoEEoiI I lw lll.f... LEE .. 5 .. 0 .L 1L. IL 1111L5 111111.4 1 6 MICROCOPY RESOLUTION TEST CHART NATIONAL...KEY WORDS (Continue on reverse side it necessay and identiy by block num~ber) Information, Find, Data, and Resource. 5 24L AfNrAC? (Cmhueen erm a t... 5 Central Intelligence Agency (CIA) Publications ............... 6 Data Item Description (DID) .................................. 7 Defense

MAPK Regulation of IL-4/-13 Receptors Contributes to the Synergistic Increase in CCL11/Eotaxin-1 in Response to TGF-β1 and IL-13 in Human Airway Fibroblasts

PubMed Central

Zhou, Xiuxia; Hu, Haizhen; Balzar, Silvana; Trudeau, John B.; Wenzel, Sally E.

2012-01-01

CCL11/eotaxin-1 is a potent eosinophilic CC chemokine expressed by primary human fibroblasts. The combination of TGF-β1 and IL-13 synergistically increases CCL11 expression, but the mechanisms behind the synergy are unclear. To address this, human airway fibroblast cultures from normal and asthmatic subjects were exposed to IL-13 alone or TGF-β1 plus IL-13. Transcriptional (nuclear run-on) and post-transcriptional (mRNA stability) assays confirmed that transcriptional regulation is critical for synergistic expression of CCL11. TGF-β1 plus IL-13 synergistically increased STAT-6 phosphorylation, nuclear translocation and binding to the CCL11 promoter as compared to IL-13 alone. STAT-6 siRNA significantly knocked down both STAT-6 mRNA expression and phosphorylation, and inhibited CCL11 mRNA and protein expression. Regulation of the IL-4 receptor α (IL-4Rα) complex by TGF-β1 augmented IL-13 signaling by dampening IL-13 receptor α2 (IL-13Rα2) expression, overcoming IL-13's autoregulation of its pathway and enhancing the expression of CCL11. Our data suggest that TGF-β1 induced activation of the MEK-ERK pathway reduces IL-13Rα2 expression induced by IL-13. Thus, TGF-β1, a pleiotropic cytokine upregulated in asthmatic airways, can augment eosinophilic inflammation by interfering with IL-13's negative feedback autoregulatory loop under MEK/ERK dependent conditions. PMID:22573806

Impact of caspase-1/11, -3, -7, or IL-1β/IL-18 deficiency on rabies virus-induced macrophage cell death and onset of disease.

PubMed

Kip, E; Nazé, F; Suin, V; Vanden Berghe, T; Francart, A; Lamoral, S; Vandenabeele, P; Beyaert, R; Van Gucht, S; Kalai, M

2017-01-01

Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn-Rotnycki-Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals. Infection of Mf4/4 macrophages with both strains led to caspase-1 activation and IL-1 β and IL-18 production, as well as activation of caspases-3, -7, -8, and -9. Moreover, absence of caspase-3, but not of caspase-1 and -11 or -7, partially inhibited virus-induced cell death of bone marrow-derived macrophages. Intranasal inoculation with CVS-11 of mice deficient for either caspase-1 and -11 or -7 or both IL-1 β and IL-18 led to general brain infection and lethal disease similar to wild-type mice. Deficiency of caspase-3, on the other hand, significantly delayed the onset of disease, but did not prevent final lethal outcome. Interestingly, deficiency of caspase-1/11, the key executioner of pyroptosis, aggravated disease severity caused by ERA virus, whereas wild-type mice or mice deficient for either caspase-3, -7, or both IL-1 β and IL-18 presented the typical mild symptoms associated with ERA virus. In conclusion, rabies virus infection of macrophages induces caspase-1- and caspase-3-dependent cell death. In vivo caspase-1/11 and caspase-3 differently affect disease development in response to infection with the attenuated ERA strain or the virulent CVS-11 strain, respectively. Inflammatory caspases seem to control attenuated rabies virus infection, while caspase-3 aggravates virulent rabies virus infection.

The structure of free L11 and functional dynamics of L11 in free, L11-rRNA(58 nt) binary and L11-rRNA(58 nt)-thiostrepton ternary complexes.

PubMed

Lee, Donghan; Walsh, Joseph D; Yu, Ping; Markus, Michelle A; Choli-Papadopoulou, Theodora; Schwieters, Charles D; Krueger, Susan; Draper, David E; Wang, Yun-Xing

2007-04-06

The L11 binding site is one of the most important functional sites in the ribosome. The N-terminal domain of L11 has been implicated as a "reversible switch" in facilitating the coordinated movements associated with EF-G-driven GTP hydrolysis. The reversible switch mechanism has been hypothesized to require conformational flexibility involving re-orientation and re-positioning of the two L11 domains, and warrants a close examination of the structure and dynamics of L11. Here we report the solution structure of free L11, and relaxation studies of free L11, L11 complexed to its 58 nt RNA recognition site, and L11 in a ternary complex with the RNA and thiostrepton antibiotic. The binding site of thiostrepton on L11 was also defined by analysis of structural and dynamics data and chemical shift mapping. The conclusions of this work are as follows: first, the binding of L11 to RNA leads to sizable conformation changes in the regions flanking the linker and in the hinge area that links a beta-sheet and a 3(10)-helix-turn-helix element in the N terminus. Concurrently, the change in the relative orientation may lead to re-positioning of the N terminus, as implied by a decrease of radius of gyration from 18.5 A to 16.2 A. Second, the regions, which undergo large conformation changes, exhibit motions on milliseconds-microseconds or nanoseconds-picoseconds time scales. Third, binding of thiostrepton results in more rigid conformations near the linker (Thr71) and near its putative binding site (Leu12). Lastly, conformational changes in the putative thiostrepton binding site are implicated by the re-emergence of cross-correlation peaks in the spectrum of the ternary complex, which were missing in that of the binary complex. Our combined analysis of both the chemical shift perturbation and dynamics data clearly indicates that thiostrepton binds to a pocket involving residues in the 3(10)-helix in L11.

The Structure of Free L11 and Functional Dynamics of L11 in Free, L11-rRNA(58nt) Binary and L11-rRNA(58nt)-thiostrepton Ternary Complexes

PubMed Central

Lee, Donghan; Walsh, Joseph D.; Yu, Ping; Markus, Michelle A.; Choli-Papadopoulou, Theodora; Schwieters, Charles D.; Krueger, Susan; Draper, David E.; Wang, Yun-Xing

2007-01-01

Summary The L11 binding site is one of the most important functional sites in the ribosome. The N-terminal domain of L11 has been implicated as a “reversible switch” in facilitating the coordinated movements associated with EF-G–driven GTP hydrolysis. The “reversible switch” mechanism has been hypothesized to require conformational flexibility involving re-orientation and re-positioning of the two L11 domains, and warrants a close examination of the structure and dynamics of L11. Here we report the solution structure of free L11, and relaxation studies of free L11, L11complexed to its 58 nt RNA recognition site, and L11 in a ternary complex with the RNA and thiostrepton antibiotic. The binding site of thiostrepton on L11 was also defined by analysis of structural and dynamics data and chemical shift mapping. The conclusions of this work are as follows: First, the binding of L11 to RNA leads to sizable conformation changes in the regions flanking the linker and in the hinge area that links a β-sheets and a 310-helix-turn-helix element in the N-terminus. Concurrently, the change in the relative orientation may lead to re-positioning of the N-terminus, as implied by a decrease of radius of gyration from 18.5 Å to 16.2 Å. Second, the regions, which undergo large conformation changes, exhibit motions on ms-μs or ns-ps time scales. Third, binding of thiostrepton results in more rigid conformations near the linker (Thr71) and near its putative binding site (Leu12). Lastly, conformational changes in the putative thiostrepton binding site are implicated by the re-emergence of cross-correlation peaks in the spectrum of the ternary complex, which were missing in that of the binary complex. Our combined analysis of both the chemical shift perturbation and dynamics data clearly indicates that thiostrepton binds to a pocket involving residues in the 310-helix in L11. PMID:17292917

CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells.

PubMed

Haas, Jan D; González, Frano H Malinarich; Schmitz, Susanne; Chennupati, Vijaykumar; Föhse, Lisa; Kremmer, Elisabeth; Förster, Reinhold; Prinz, Immo

2009-12-01

Gammadelta T cells are a potent source of innate IL-17A and IFN-gamma, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24(low) CD44(high) effector gammadelta T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ gammadelta T cells produced IL-17A, while NK1.1+ gammadelta T cells were efficient producers of IFN-gamma but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ gammadelta T cells. Accordingly, both gammadelta T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-gamma in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-gamma and IL-23 induced IL-17A production by NK1.1+ or CCR6+ gammadelta T cells, respectively. Importantly, we show that CCR6+ gammadelta T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL-17A-producing gammadelta T cells derive from less TCR-dependent selection events than IFN-gamma-producing NK1.1+ gammadelta T cells.

TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population

PubMed Central

García-Ramírez, Román Alejandro; Ramírez-Venegas, Alejandra; Quintana-Carrillo, Roger; Camarena, Ángel Eduardo; Falfán-Valencia, Ramcés; Mejía-Aranguré, Juan Manuel

2015-01-01

Background Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection. Methods 145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100. Results The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05–11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p  =  0.007) levels. Conclusions The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were

BIP induces mice CD19(hi) regulatory B cells producing IL-10 and highly expressing PD-L1, FasL.

PubMed

Tang, Youfa; Jiang, Qing; Ou, Yanghui; Zhang, Fan; Qing, Kai; Sun, Yuanli; Lu, Wenjie; Zhu, Huifen; Gong, Feili; Lei, Ping; Shen, Guanxin

2016-01-01

Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions. Copyright © 2015. Published by Elsevier Ltd.

IL-11 and CCL-1: Novel Protein Diagnostic Biomarkers of Lung Adenocarcinoma in Bronchoalveolar Lavage Fluid (BALF).

PubMed

Pastor, Maria Delores; Nogal, Ana; Molina-Pinelo, Sonia; Quintanal-Villalonga, Álvaro; Meléndez, Ricardo; Ferrer, I; Romero-Romero, Beatrice; De Miguel, Maria José; López-Campos, José Luis; Corral, Jesús; García-Carboner, Rocío; Carnero, Amancio; Paz-Ares, Luis

2016-12-01

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are smoking-related diseases, with the presence of COPD itself increasing the risk for development of LC, probably owing to underlying inflammation. LC is typically detected at late stages of the disease and carries a poor prognosis. There is an unmet need for methods to facilitate the early detection of LC in high-risk subjects such as smokers. The expression of inflammatory proteins in bronchoalveolar lavage fluid (BALF) samples was studied by antibody arrays in a prospective cohort of 60 smokers of more than 30 pack-years divided into four groups (control, patients with LC, patients with COPD, and patients with LC plus COPD). Relevant biomarkers were validated by Western blot. Additional validation with enzyme-linked immunosorbent assay (ELISA) was carried out on two independent controlled cohorts of 139 patients (control, patients with LC, patients with COPD, and patients with LC plus COPD) and 160 patients (control and patients with LC of all histological types). A total of 16 differentially expressed proteins in samples from patients with LC, COPD, and LC plus COPD were identified by antibody arrays and validated by Western blot and ELISA. C-C motif chemokine ligand 1 (CCL-1) and interleukin-11 (IL)-11 were selectively expressed in samples from patients with adenocarcinoma with or without COPD (p < 0.005). These proteins exhibited a remarkable diagnostic performance for lung adenocarcinoma in an independent cohort of 139 patients. Receiver operating characteristic curves showed that the optimum diagnostic cutoff value for IL-11 was 42 pg/mL (area under the curve = 0.93 [95% confidence interval: 0.896-0.975], sensitivity 90%, specificity 86%), whereas for CCL-1 it was 39.5 pg/mL (0.83 [95% confidence interval: 0.749-0.902], sensitivity 83%, and specificity 74%). Further validation of the ELISA biomarkers at the aforementioned cutoffs was performed in an additional cohort of 160 patients (20

SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

PubMed

Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

2010-01-01

Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

[Cytokines and malaria. A study of TNF-alpha, IL1-beta, IL6 and IL2R in 28 patients].

PubMed

Nicolas, P; Hovette, P; Merouze, F; Touze, J E; Martet, G

1994-01-01

Authors have studied TNF alpha, IL1 bêta, IL6 and RIL2s in 28 malaria illness patients. Increased levels of TNF, IL1 bêta and RIL2s in serum, are observed on admission to hospital. These cytokine levels are decreased, eight days later, after patients are treated. In discussion, TNF levels as a prognosis component is evocated.

U.S. EPA, Pesticide Product Label, MYCOTROL ES, 11/13/2008

EPA Pesticide Factsheets

2011-04-21

... rL"plr~iI,'r Ille·l·tillg .\\iII)SI I sl~llldards nfa( kast R-'):'i or Pl)5. Rq)~alCd L'XpOSUI\\' III hit!h l'PllcL'llIr:lliull:' pI" 1l1l .... Ttihl:!I 111"1)IL'II1:-. (:llll';ltl:-'l' alh . ...

Causes and Corrections for Propeller-Excited Airborne Noise on a Naval Auxiliary Oiler.

DTIC Science & Technology

1983-11-01

17 1 sas ri-IMFUtei tii llaii tilt- a,, D) = 01519 (at tip)) ~it., eptalil 1iii0i Ik-%(b ,I all 1 .11 Ill Ill MWi gisi I(il/il \\ ifiratioII Isi ’,~t...slipi aind suet Scopue iii, ltinil. ts r li. 1 It,,Aso, -i trl-rar- ratiorr ii. 𔃻 ) = 12 Thui prirs I it( ,fi - i t l-sigt intiirf riat ioin Ifor I i...gir, rimi- tri isi -tatritr pririlrtii 12:1. ililt-atlios:ii, 11 111 iG-, Ir411ir and %tiiii i il lttfr loi- -2 1 , .11"l tin.1 dtriri ot prrii-livr

Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens.

PubMed

Karjalainen, Katja; Jaalouk, Diana E; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H P; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J; O'Brien, Susan; Kantarjian, Hagop M; Cortes, Jorge E; Calin, George A; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-07-01

The IL11 receptor (IL11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors, such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here, we evaluated the IL11R as a candidate therapeutic target in human leukemia and lymphoma. First, we show that the IL11R protein is expressed in a variety of human leukemia- and lymphoma-derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, whereas expression is absent from nonmalignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analogue with an apparent improved antileukemia cell profile. These results indicate (i) that the IL11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. ©2015 American Association for Cancer Research.

U.S. EPA, Pesticide Product Label, , 12/14/1982

EPA Pesticide Factsheets

2011-04-21

... l \\. , • t • ,. • • r , J L 1I.I:~dlll:;, '1\\\\ 1111111,111: .. \\1111 1>I\\II1(,:;t i~' .\\111111.11· DANGER I!armful if sw.lllow,·d. I,void I".·"lhillq v.ll"»·"

Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway.

PubMed

Cook, Ian H; Evans, Jemma; Maldonado-Pérez, David; Critchley, Hilary O; Sales, Kurt J; Jabbour, Henry N

2010-03-01

Prokineticin-1 (PROK1) is a multifunctional secreted protein which signals via the G-protein coupled receptor, PROKR1. Previous data from our laboratory using a human genome survey microarray showed that PROK1-prokineticin receptor 1 (PROKR1) signalling regulates numerous genes important for establishment of early pregnancy, including the cytokine interleukin (IL)-11. Here, we have shown that PROK1-PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua via the calcium-calcineurin signalling pathway in a guanine nucleotide-binding protein (G(q/11)), extracellular signal-regulated kinases, Ca(2+) and calcineurin-nuclear factor of activated T cells dependent manner. Conversely, treatment of human decidua with a lentiviral miRNA to abolish endogenous PROK1 expression results in a significant reduction in IL-11 expression and secretion. Importantly, we have also shown a regulatory role for the regulator of calcineurin 1 isoform 4 (RCAN1-4). Overexpression of RCAN1-4 in PROKR1 Ishikawa cells using an adenovirus leads to a reduction in PROK1 induced IL-11 indicating that RCAN1-4 is a negative regulator in the calcineurin-mediated signalling to IL-11. Finally, we have shown the potential for both autocrine and paracrine signalling in the human endometrium by co-localizing IL-11, IL-11Ralpha and PROKR1 within the stromal and glandular epithelial cells of non-pregnant endometrium and first trimester decidua. Overall we have identified and characterized the signalling components of a novel PROK1-PROKR1 signalling pathway regulating IL-11.

Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway

PubMed Central

Cook, Ian H.; Evans, Jemma; Maldonado-Pérez, David; Critchley, Hilary O.; Sales, Kurt J.; Jabbour, Henry N.

2010-01-01

Prokineticin-1 (PROK1) is a multifunctional secreted protein which signals via the G-protein coupled receptor, PROKR1. Previous data from our laboratory using a human genome survey microarray showed that PROK1–prokineticin receptor 1 (PROKR1) signalling regulates numerous genes important for establishment of early pregnancy, including the cytokine interleukin (IL)-11. Here, we have shown that PROK1–PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua via the calcium–calcineurin signalling pathway in a guanine nucleotide-binding protein (Gq/11), extracellular signal-regulated kinases, Ca2+ and calcineurin–nuclear factor of activated T cells dependent manner. Conversely, treatment of human decidua with a lentiviral miRNA to abolish endogenous PROK1 expression results in a significant reduction in IL-11 expression and secretion. Importantly, we have also shown a regulatory role for the regulator of calcineurin 1 isoform 4 (RCAN1-4). Overexpression of RCAN1-4 in PROKR1 Ishikawa cells using an adenovirus leads to a reduction in PROK1 induced IL-11 indicating that RCAN1-4 is a negative regulator in the calcineurin-mediated signalling to IL-11. Finally, we have shown the potential for both autocrine and paracrine signalling in the human endometrium by co-localizing IL-11, IL-11Rα and PROKR1 within the stromal and glandular epithelial cells of non-pregnant endometrium and first trimester decidua. Overall we have identified and characterized the signalling components of a novel PROK1–PROKR1 signalling pathway regulating IL-11. PMID:19801577

Antibody-based delivery of tumor necrosis factor (L19-TNFα) and interleukin-2 (L19-IL2) to tumor-associated blood vessels has potent immunological and anticancer activity in the syngeneic J558L BALB/c myeloma model.

PubMed

Menssen, Hans D; Harnack, Ulf; Erben, Ulrike; Neri, Dario; Hirsch, Burkhard; Dürkop, Horst

2018-03-01

To analyze the impact of TNFα or IL2 on human lymphocytes in vitro and the anti-tumor and immune-modifying effects of L19-IL2 and L19-TNFα on subcutaneously growing J558L myeloma in immunocompetent mice. PBMCs from three healthy volunteers were incubated with IL2, TNFα, or with IL2 plus addition of TNFα (final 20 h). BALB/c J558L mice with subcutaneous tumors were treated with intravenous L19-TNFα plus L19-IL2, or controls. Tumor growth and intra- and peri-tumoral tissues were analyzed for micro-vessel density, necrosis, immune cell composition, and PD1 or PD-L1 expressing cells. Exposure of PBMC in vitro to IL2, TNFα, or to IL2 over 3 and 5 days plus TNFα for the final 20 h resulted in an approximately 50 and 75% reduction of the CD25low effector cell/CD25high Treg cell ratio, respectively, compared to medium control. IL2 or TNFα increased the proportion of CD4- CD25low effector lymphocytes while reducing the proportion of CD4+ CD25low Teff cells. In the J558L myeloma model, tumor eradication was observed in 58, 42, 25, and 0% of mice treated with L19-TNFα plus L19-IL2, L19-TNFα, L19-IL2, and PBS, respectively. L19-TNFα/L19-IL2 combination caused tumor necrosis, capillary density doubling, peri-tumoral T cell and PD1+ T cell reduction (- 50%), and an increase in PD-L1+ myeloma cells. IL2, TNFα, or IL2 plus TNFα (final 20 h) increased the proportion of CD4- CD25low effector lymphocytes possibly indicating immune activation. L19-TNFα/L19-IL2 combination therapy eradicated tumors in J558L myeloma BALB/c mice likely via TNFα-induced tumor necrosis and L19-TNFα/L19-IL2-mediated local cellular immune reactions.

The X11L/X11{beta}/MINT2 and X11L2/X11{gamma}/MINT3 scaffold proteins shuttle between the nucleus and cytoplasm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumioka, Akio; Saito, Yuhki; Sakuma, Megumi

2008-03-10

The X11/MINT family proteins are adaptor scaffolding proteins involved in formation of multiprotein complexes, and trafficking and metabolism of membrane proteins such as the beta-amyloid precursor protein. We found that a significant portion of X11L and X11L2 are recovered in nuclear fraction of mouse brain homogenates. EGFP-X11s were not detected in the nucleus of N2a neuroblastoma cells; however, administration of leptomycin B (LMB) induced substantial nuclear accumulation of EGFP-X11L and EGFP-X11L2, while EGFP-X11 showed little accumulation. Fluorescence loss in photobleaching (FLIP) analysis indicated that EGFP-X11L2 and EGFP-X11L are shuttled between the cytoplasm and nucleus, the former more effectively than themore » latter. We identified a nuclear export signal (NES) in the N-terminus of X11L2, mutation of which induces nuclear accumulation of EGFP-X11L2 in the absence of LMB. X11L2 fused to the Gal4 DNA binding domain (DBD) showed transcriptional activity, suggesting that X11L2 could function as a transcriptional activator if tethered near a promoter. Interestingly, attenuation of the nucleo-cytoplasmic shuttling of GAL4-DBD-X11L2 by mutating the NES or attaching the SV40 nuclear localization signal significantly decreased the apparent transcriptional activity. Our observations suggest that X11L2 functions in the nucleus by a mechanism distinct from conventional transactivators.« less

STAT3 and STAT1 mediate IL-11–dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice

PubMed Central

Ernst, Matthias; Najdovska, Meri; Grail, Dianne; Lundgren-May, Therese; Buchert, Michael; Tye, Hazel; Matthews, Vance B.; Armes, Jane; Bhathal, Prithi S.; Hughes, Norman R.; Marcusson, Eric G.; Karras, James G.; Na, Songqing; Sedgwick, Jonathon D.; Hertzog, Paul J.; Jenkins, Brendan J.

2008-01-01

Deregulated activation of STAT3 is frequently associated with many human hematological and epithelial malignancies, including gastric cancer. While exaggerated STAT3 signaling facilitates an antiapoptotic, proangiogenic, and proproliferative environment for neoplastic cells, the molecular mechanisms leading to STAT3 hyperactivation remain poorly understood. Using the gp130Y757F/Y757F mouse model of gastric cancer, which carries a mutated gp130 cytokine receptor signaling subunit that cannot bind the negative regulator of cytokine signaling SOCS3 and is characterized by hyperactivation of the signaling molecules STAT1 and STAT3, we have provided genetic evidence that IL-11 promotes chronic gastric inflammation and associated tumorigenesis. Expression of IL-11 was increased in gastric tumors in gp130Y757F/Y757F mice, when compared with unaffected gastric tissue in wild-type mice, while gp130Y757F/Y757F mice lacking the IL-11 ligand–binding receptor subunit (IL-11Rα) showed normal gastric STAT3 activation and IL-11 expression and failed to develop gastric tumors. Furthermore, reducing STAT3 activity in gp130Y757F/Y757F mice, either genetically or by therapeutic administration of STAT3 antisense oligonucleotides, normalized gastric IL-11 expression and alleviated gastric tumor burden. Surprisingly, the genetic reduction of STAT1 expression also reduced gastric tumorigenesis in gp130Y757F/Y757F mice and coincided with reduced gastric inflammation and IL-11 expression. Collectively, our data have identified IL-11 as a crucial cytokine promoting chronic gastric inflammation and associated tumorigenesis mediated by excessive activation of STAT3 and STAT1. PMID:18431520

Lnk adaptor suppresses radiation resistance and radiation-induced B-cell malignancies by inhibiting IL-11 signaling

PubMed Central

Louria-Hayon, Igal; Frelin, Catherine; Ruston, Julie; Gish, Gerald; Jin, Jing; Kofler, Michael M.; Lambert, Jean-Philippe; Adissu, Hibret A.; Milyavsky, Michael; Herrington, Robert; Minden, Mark D.; Dick, John E.; Gingras, Anne-Claude; Iscove, Norman N.; Pawson, Tony

2013-01-01

The Lnk (Sh2b3) adaptor protein dampens the response of hematopoietic stem cells and progenitors (HSPCs) to a variety of cytokines by inhibiting JAK2 signaling. As a consequence, Lnk−/− mice develop hematopoietic hyperplasia, which progresses to a phenotype resembling the nonacute phase of myeloproliferative neoplasm. In addition, Lnk mutations have been identified in human myeloproliferative neoplasms and acute leukemia. We find that Lnk suppresses the development of radiation-induced acute B-cell malignancies in mice. Lnk-deficient HSPCs recover more effectively from irradiation than their wild-type counterparts, and this resistance of Lnk−/− HSPCs to radiation underlies the subsequent emergence of leukemia. A search for the mechanism responsible for radiation resistance identified the cytokine IL-11 as being critical for the ability of Lnk−/− HSPCs to recover from irradiation and subsequently become leukemic. In IL-11 signaling, wild-type Lnk suppresses tyrosine phosphorylation of the Src homology region 2 domain-containing phosphatase-2/protein tyrosine phosphatase nonreceptor type 11 and its association with the growth factor receptor-bound protein 2, as well as activation of the Erk MAP kinase pathway. Indeed, Src homology region 2 domain-containing phosphatase-2 has a binding motif for the Lnk Src Homology 2 domain that is phosphorylated in response to IL-11 stimulation. IL-11 therefore drives a pathway that enhances HSPC radioresistance and radiation-induced B-cell malignancies, but is normally attenuated by the inhibitory adaptor Lnk. PMID:24297922

Identification of an IL-17–producing NK1.1neg iNKT cell population involved in airway neutrophilia

PubMed Central

Michel, Marie-Laure; Keller, Alexandre Castro; Paget, Christophe; Fujio, Masakazu; Trottein, François; Savage, Paul B.; Wong, Chi-Huey; Schneider, Elke; Dy, Michel; Leite-de-Moraes, Maria C.

2007-01-01

Invariant natural killer T (iNKT) cells are an important source of both T helper type 1 (Th1) and Th2 cytokines, through which they can exert beneficial, as well as deleterious, effects in a variety of inflammatory diseases. This functional heterogeneity raises the question of how far phenotypically distinct subpopulations are responsible for such contrasting activities. In this study, we identify a particular set of iNKT cells that lack the NK1.1 marker (NK1.1neg) and secrete high amounts of interleukin (IL)-17 and low levels of interferon (IFN)-γ and IL-4. NK1.1neg iNKT cells produce IL-17 upon synthetic (α-galactosylceramide [α-GalCer] or PBS-57), as well as natural (lipopolysaccharides or glycolipids derived from Sphingomonas wittichii and Borrelia burgdorferi), ligand stimulation. NK1.1neg iNKT cells are more frequent in the lung, which is consistent with a role in the natural immunity to inhaled antigens. Indeed, airway neutrophilia induced by α-GalCer or lipopolysaccharide instillation was significantly reduced in iNKT-cell–deficient Jα18−/− mice, which produced significantly less IL-17 in their bronchoalveolar lavage fluid than wild-type controls. Furthermore, airway neutrophilia was abolished by a single treatment with neutralizing monoclonal antibody against IL-17 before α-GalCer administration. Collectively, our findings reveal that NK1.1neg iNKT lymphocytes represent a new population of IL-17–producing cells that can contribute to neutrophil recruitment through preferential IL-17 secretion. PMID:17470641

Increased serum levels of eotaxin/CCL11 in late-stage patients with bipolar disorder: An accelerated aging biomarker?

PubMed

Panizzutti, B; Gubert, C; Schuh, A L; Ferrari, P; Bristot, G; Fries, G R; Massuda, R; Walz, J; Rocha, N P; Berk, M; Teixeira, A L; Gama, C S

2015-08-15

Bipolar disorder (BD) is commonly comorbid with many medical disorders including atopy, and appears characterized by progressive social, neurobiological, and functional impairment associated with increasing number of episodes and illness duration. Early and late stages of BD may present different biological features and may therefore require different treatment strategies. Consequently, the aim of this study was to evaluate serum levels of eotaxin/CCL11, eotaxin-2/CCL24, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFNγ, BDNF, TBARS, carbonyl, and GPx in a sample of euthymic patients with BD at early and late stages compared to controls. Early-stage BD patients, 12 late-stage patients, and 25 controls matched for sex and age were selected. 10mL of peripheral blood was drawn from all subjects by venipuncture. Serum levels of BDNF, TBARS, carbonyl content, glutathione-peroxidase activity (GPx), cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFNγ), and chemokines (eotaxin/CCL11 and eotaxin-2/CCL24) were measured. There were no demographic differences between patients and controls. No significant differences were found for any of the biomarkers, except chemokine eotaxin/CCL11, whose serum levels were higher in late-stage patients with BD when compared to controls (p=0.022; Mann-Whitney U test). Small number of subjects and use of medication may have influenced in our results. The present study suggests a link between biomarkers of atopy and eosinophil function and bipolar disorder. These findings are also in line with progressive biological changes partially mediated by inflammatory imbalance, a process referred to as neuroprogression. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated IL-17A and IL-22 regulate expression of inducible CD38 and Zap-70 in chronic lymphocytic leukemia.

PubMed

Kouzegaran, Samaneh; Siroosbakht, Soheila; Farsad, Bahram Fariborz; Rezakhaniha, Bijan; Dormanesh, Banafshe; Behnod, Vahid; Tanha, Amir Saber

2018-01-01

In this study, we investigated the role and expression of interleukin (IL)-17A and IL-22 in chronic lymphocytic leukemia. We evaluated the expression of markers above on CLL by ELISA, qRT-PCR, flow cytometric analysis and nonparametric Kruskal-Wallis test. Quantitative RT-PCR revealed that the mRNA levels of IL-17A and IL-22 in PBMCs of CLL patients were upregulated compared with those from healthy subjects (mean ± SD: 1.96 ± 0.232 vs.0.72 ± 0.15, P < 0.001 and mean ± SD: 2.45 ± 0.534 vs.0.81 ± 0.26, P < 0.001, respectivily). In addition, findings showed that the IL-17A and IL-22 plasma level was significantly elevated than that from healthy control group (P  < 0.001). The median IL-17A and IL-22 in CLL patients and healthy control group were 48.28 ± 17.2 pg mL -1 ; 20.01 ± 11.16 pg mL -1 and 58.68 ± 23.4 pg mL -1 ;16.47 ± 10.31 P < 0.001, respectively. The levels of IL-17A and IL-22 was not significantly associated with the different stages of disease (Rai stages; Kruskal-Wallis test P > 0.05).No significant relationship was found between expression of CD38 and higher median serum levels of IL-17A in patients, but patients with negative expression of ZAP-70 showed a significant association with higher median serum levels of IL-17A compared with healthy subjects. (57.84 pg mL -1 vs. 31.67 pg mL -1 ; P = 0.016). IL-22 is elevated and associated with CD38 and Zap-70 expression in patients with CLL. No significant correlation was found between expression of CD38 and increased levels of IL-17A, negative expression of ZAP-70 showed a significant association with increased levels of IL-17A. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

A Novel Mechanism of γ-Irradiation-Induced IL-6 Production Mediated by P2Y11 Receptor in Epidermal Keratinocytes.

PubMed

Ohsaki, Airi; Miyano, Yuki; Tanaka, Rei; Tanuma, Sei-Ichi; Kojima, Shuji; Tsukimoto, Mitsutoshi

2018-06-01

Skin inflammation is caused by excessive production of cytokines and chemokines in response to an external stimulus, such as radiation, but the mechanisms involved are not completely understood. Here, we report a novel mechanism of γ-irradiation-induced interleukin-6 (IL-6) production mediated by P2Y11 receptors in epidermal cells. After irradiation of HaCaT cells derived from human epidermal keratinocytes with 5 Gy of γ-rays ( 137 Cs: 0.78 Gy/min), IL-6 production was unchanged at 24 h after γ-irradiation, but was increased at 48 h. IL-6 mRNA was increased at 30 h, and IL-6 production was increased at 33 h after irradiation. The production of IL-6 was sustained at least for 4 d after irradiation. P2Y11 receptor antagonist NF157 inhibited IL-6 production in irradiated cells. Treatment with ATP, a ligand of P2Y11 receptor caused IL-6 production within 24 h. ATP-induced IL-6 production was also suppressed by NF157. Extracellular ATP level was increased after irradiation. The p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling was involved in the production of IL-6 at the downstream of P2Y11 receptor activation. In addition, the cell cycle was arrested at the G2/M phase, and DNA repair foci were not disappeared at 48 h after γ-irradiation. The protein level of histone methylation enzyme G9a, which inhibits IL-6 production, was decreased after γ-irradiation. In conclusion, we suggest that γ-irradiation induces sustained IL-6 production in HaCaT cells from 33 h after irradiation, which is mediated through P2Y11 receptor-p38 MAPK-NF-κB signaling pathway and G9a degradation. This is a novel mechanism of cytokine production in γ-irradiated cells.

[Effects of lipopolysaccharides extracted from Porphyromonas endodontalis on the expression of IL-1beta mRNA and IL-6 mRNA in osteoblasts].

PubMed

Yang, Di; Li, Ren; Qiu, Li-Hong; Li, Chen

2009-04-01

To quantify the IL-1 beta mRNA and IL-6 mRNA expression induced by lipopolysaccharides (LPS)extracted from Porphyromonas endodontalis(P.e) in osteoblasts, and to relate P.e-LPS to bone absorption pathogenesis in lesions of chronical apical periodontitis. MG63 was treated with different concentrations of P.e-LPS(0-50 microg/mL) for different hours(0-24h). The expression of IL-1 beta mRNA and IL-6 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR).Statistical analysis was performed using one- way ANOVA and Dunnett t test with SPSS11.0 software package. The level of IL-1 beta mRNA and IL-6 mRNA increased significantly after treatment with P.e-LPS at more than 5 microg/mL (P<0.01)and for more than 1 hour (P<0.01), which indicated that P.e-LPS induced osteoblasts to express IL-1 beta mRNA and IL-6 mRNA in dose and time dependent manners. P.e-LPS may promote bone resorption in lesions of chronical apical periodontitis by inducing IL-1 beta mRNA and IL-6 mRNA expression in osteoblasts.

U.S. EPA, Pesticide Product Label, FRUIT BUILDER'S FISH OIL PESTICIDE/STICKER-SPREADER, 11/06/1981

EPA Pesticide Factsheets

2011-04-21

... 'E;'<1 .... : f''':.l ':, • 'l I,) ,Ih':i I:, th •. (~"I:"L'd t!:,..rl,;,]nt ~ldge of l)lLJ d·. Jt'icprnt..!It ,)! tll'~ ute of IL) ,) iLl" ·n~, ;)1 Olt I'f" 'I' J.JI!,Jr': .. 'j' .... n (j hi! ...

Exercise Prevents Mental Illness

NASA Astrophysics Data System (ADS)

Purnomo, K. I.; Doewes, M.; Giri, M. K. W.; Setiawan, K. H.; Wibowo, I. P. A.

2017-03-01

Multiple current studies show that neuroinflammation may contribute to mental illness such as depression, anxiety, and mood disorder. Chronic inflammation in peripheral tissues is indicated by the increase of inflammatory marker like cytokine IL-6, TNF-α, and IL-1β. Pro-inflammatory cytokine in peripheral tissues can reach brain tissues and activate microglia and it causes neuroinflammation. Psychological stress may led peripheral and central inflammation. Activated microglia will produce pro-inflammatory cytokine, ROS, RNS, and tryptophan catabolizes. This neuroinflammation can promote metabolism changes of any neurotransmitter, such as serotonin, dopamine, and glutamate that will influence neurocircuit in the brain including basal ganglia and anterior cingulated cortex. It leads to mental illness. Exercise give contribution to reduce tissue inflammation. When muscle is contracting in an exercise, muscle will produce the secretion of cytokine like IL-6, IL-1ra, and IL-10. It will react as anti-inflammation and influence macrophage, T cell, monosit, protein Toll-Like Receptor (TLR), and then reduce neuroinflammation, characterised by the decrease of pro-inflammatory cytokine and prevent the activation of microglia in the brain. The objective of the present study is to review scientific articles in the literature related to the contribution of exercise to prevent and ease mental illness.

Inflammatory cytokines IL-17 and TNF-α up-regulate PD-L1 expression in human prostate and colon cancer cells.

PubMed

Wang, Xun; Yang, Lingyun; Huang, Feng; Zhang, Qiuyang; Liu, Sen; Ma, Lin; You, Zongbing

2017-04-01

Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) are co-expressed by T helper 17 (T H 17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-α may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells. TNF-α induced PD-L1 mRNA and protein expression in both cell lines. Neither IL-17 nor TNF-α induced PD-L2 mRNA or protein expression. IL-17 and TNF-α acted individually rather than cooperatively in induction of PD-L1 expression. IL-17 and/or TNF-α activated AKT, nuclear factor-κB (NF-κB), and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways in HCT116 cells, whereas only NF-κB signaling was activated in LNCaP cells. NF-κB inhibitor could diminish PD-L1 protein expression induced by IL-17 and/or TNF-α in both HCT116 and LNCaP cell lines. ERK1/2 inhibitor could also reduce PD-L1 protein expression induced by IL-17 and/or TNF-α in HCT116 cells, while AKT inhibitor could abolish PD-L1 protein expression induced by IL-17 and/or TNF-α in LNCaP cells. These results suggest that IL-17 and TNF-α act individually rather than cooperatively through activation of NF-κB and ERK1/2 signaling to up-regulate PD-L1 expression in HCT116 cells, while the two inflammatory cytokines act through activation of NF-κB signaling, in the presence of AKT activity, to up-regulate PD-L1 expression in LNCaP cells. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Inflammatory cytokines IL-17 and TNF-α up-regulate PD-L1 expression in human prostate and colon cancer cells

PubMed Central

Wang, Xun; Yang, Lingyun; Huang, Feng; Zhang, Qiuyang; Liu, Sen; Ma, Lin; You, Zongbing

2017-01-01

Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) are co-expressed by T helper 17 (TH17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-α may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells. TNF-α induced PD-L1 mRNA and protein expression in both cell lines. Neither IL-17 nor TNF-α induced PD-L2 mRNA or protein expression. IL-17 and TNF-α acted individually rather than cooperatively in induction of PD-L1 expression. IL-17 and/or TNF-α activated AKT, nuclear factor-κB (NF-κB), and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways in HCT116 cells, whereas only NF-κB signaling was activated in LNCaP cells. NF-κB inhibitor could diminish PD-L1 protein expression induced by IL-17 and/or TNF-α in both HCT116 and LNCaP cell lines. ERK1/2 inhibitor could also reduce PD-L1 protein expression induced by IL-17 and/or TNF-α in HCT116 cells, while AKT inhibitor could abolish PD-L1 protein expression induced by IL-17 and/or TNF-α in LNCaP cells. These results suggest that IL-17 and TNF-α act individually rather than cooperatively through activation of NF-κB and ERK1/2 signaling to up-regulate PD-L1 expression in HCT116 cells, while the two inflammatory cytokines act through activation of NF-κB signaling, in the presence of AKT activity, to up-regulate PD-L1 expression in LNCaP cells. PMID:28223102

L-FABP and IL-6 as markers of chronic kidney damage in children after hemolytic uremic syndrome.

PubMed

Lipiec, Katarzyna; Adamczyk, Piotr; Świętochowska, Elżbieta; Ziora, Katarzyna; Szczepańska, Maria

2018-06-13

Hemolytic-uremic syndrome (HUS) is a form of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). From a clinical point of view, it is important to search for markers that allow for early identification of patients at risk of a poor prognosis. The study evaluated the serum and urine levels of liver-type fatty acid binding protein (L-FABP) and interleukin 6 (IL-6). The study was conducted in 29 children with a history of HUS. The relationship between L-FABP and IL-6 and anthropometric measurements, the value of estimated glomerular filtration rate (eGFR) and albuminuria were additionally evaluated. In children after HUS, L-FABP and IL-6 concentration in both serum and urine was significantly higher in comparison to the control group. No differences in L-FABP and IL-6 concentration in serum and urine depending on the type of HUS and gender were noted. Correlation between L-FABP and IL-6 in serum and urine with eGFR and urine albumin-creatinine ratio (ACR) in the total group of patients after HUS was not detected. In the group of children after 6 month observation after HUS, a negative correlation of L-FABP concentration with eGFR was found. The results indicate that the higher concentration of L-FABP in serum and urine of children with a history of HUS can be the result of protracted injury initiated during the acute phase of the disease. Lack of correlation of L-FABP concentration with the ACR may be associated with a short (less than 6 months) observation after acute renal failure or merely temporary renal tubular damage in the acute phase of the disease. In contrast, higher levels of IL-6 in serum and urine in children after HUS compared to healthy children and the negative correlation of L-FABP concentration and eGFR in children after 6 month observation after HUS may confirm their participation in CKD. Thus, L-FABP and IL-6 seem to be good biomarkers of chronic kidney damage in survivors of the acute phase of

MX Siting Investigation. Geotechnical Evaluation. Volume V. Nevada - Utah Verification Studies, FY 79. Geotechnical Data White River North CDP, Nevada.

DTIC Science & Technology

1979-08-24

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Hydraulic Component Acoustic Compatibility Study

DTIC Science & Technology

1979-10-01

401 shoiv\\ tha~t t’e \\.i iN ~i’lt is qtidtdt t liallti lel It 111111 mm 1𔃻 toI 20 k~t;. ah~w 0ki o 17 tile Hv mmdatl, i.111n i’- 111idor ~ v~ip-it 1...Iln ic 1 1 N II 1 1.o l )Ili" td 1 1iilA " 11 ,k W , 0 !l, 11 11’ l"JM !:1h l1I \\ ’l Ol 11. oI’l’u 0 1 1, ,ZIII, 𔃻N\\ 1" III ,𔃺! d ’ oI ."I 1 IN 11

Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody

PubMed Central

Fallon, Jonathan K.; Vandeveer, Amanda J.

2017-01-01

The combined therapeutic potential of an immunocytokine designed to deliver IL-12 to the necrotic regions of solid tumors with an anti-PD-L1 antibody that disrupts the immunosuppressive PD-1/PD-L1 axis yielded a combinatorial benefit in multiple murine tumor models. The murine version of the immunocytokine, NHS-muIL12, consists of an antibody (NHS76) recognizing DNA/DNA-histone complexes, fused with two molecules of murine IL-12 (NHS-muIL12). By its recognition of exposed DNA, NHS-muIL12 targets IL-12 to the necrotic portions of tumors; it has a longer plasma half-life and better antitumor efficacy against murine tumors than recombinant murine IL-12. It is shown here that NHS-muIL12, in an IFN-γ‒dependent mechanism, upregulates mPD-L1 expression on mouse tumors, which could be construed as an immunosuppressive action. Yet concurrent therapy with NHS-muIL12 and an anti-PD-L1 antibody resulted in additive/synergistic antitumor effects in PD-L1‒expressing subcutaneously transplanted tumors (MC38, MB49) and in an intravesical bladder tumor model (MB49). Antitumor efficacy correlated with (a) with a higher frequency of tumor antigen-specific splenic CD8+ T cells and (b) enhanced T cell activation over a wide range of NHS-muIL12 concentrations. These findings suggest that combining NHS-muIL12 and an anti-PD-L1 antibody enhances T cell activation and T cell effector functions within the tumor microenvironment, significantly improving overall tumor regression. These results should provide the rationale to examine the combination of these agents in clinical studies. PMID:28423552

Tetrahedral cluster and pseudo molecule: New approaches to Calculate Absolute Surface Energy of Zinc Blende (111)/(-1-1-1) Surface

NASA Astrophysics Data System (ADS)

Zhang, Yiou; Zhang, Jingzhao; Tse, Kinfai; Wong, Lun; Chan, Chunkai; Deng, Bei; Zhu, Junyi

Determining accurate absolute surface energies for polar surfaces of semiconductors has been a great challenge in decades. Here, we propose pseudo-hydrogen passivation to calculate them, using density functional theory approaches. By calculating the energy contribution from pseudo-hydrogen using either a pseudo molecule method or a tetrahedral cluster method, we obtained (111)/(-1-1-1) surfaces energies of Si, GaP, GaAs, and ZnS with high self-consistency. Our findings may greatly enhance the basic understandings of different surfaces and lead to novel strategies in the crystal growth. We would like to thank Su-huai Wei for helpful discussions. Computing resources were provided by the High Performance Cluster Computing Centre, Hong Kong Baptist University. This work was supported by the start-up funding and direct Grant with the Project.

Cytokines and metabolic patterns in pediatric patients with critical illness.

PubMed

Briassoulis, George; Venkataraman, Shekhar; Thompson, Ann

2010-01-01

It is not known if cytokines, which are cell-derived mediators released during the host immune response to stress, affect metabolic response to stress during critical illness. The aim of this prospective study was to determine whether the metabolic response to stress is related to the inflammatory interleukin-6 (IL-6), 10 (IL-10), and other stress mediators' responses and to assess their relationships with different feeding patterns, nutritional markers, the severity of illness as assessed by the Multiple Organ System Failure (MOSF), the Pediatric Risk of Mortality Score (PRISM), systemic inflammatory response syndrome (SIRS), and mortality in critically ill children. Patients were classified as hypermetabolic, normometabolic, and hypometabolic when the measured resting energy expenditures (REE) were >110%, 90-110% and, <90% of the predicted basal metabolic rate, respectively. The initial predominance of the hypometabolic pattern (48.6%) declined within 1 week of acute stress (20%), and the hypermetabolic patterns dominated only after 2 weeks (60%). Only oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) (P < .0001) but none of the cytokines and nutritional markers, were independently associated with a hypometabolic pattern. REE correlated with the IL-10 but not PRISM. In the presence of SIRS or sepsis, CRP, IL-6, IL-10, Prognostic Inflammatory and Nutritional Index (NI), and triglycerides--but not glucose, VO(2), or VCO(2) increased significantly. High IL-10 levels (P = .0000) and low measured REE (P = .0000) were independently associated with mortality (11.7%), which was higher in the hypometabolic compared to other metabolic patterns (P < .005). Our results showed that only VO(2) and VCO(2), but not IL-6 or IL-10, were associated with a hypometabolic pattern which predominated the acute phase of stress, and was associated with increased mortality. Although in SIRS or sepsis, the cytokine response was reliably reflected by increases in NI and

Cytokines and Metabolic Patterns in Pediatric Patients with Critical Illness

PubMed Central

Briassoulis, George; Venkataraman, Shekhar; Thompson, Ann

2010-01-01

It is not known if cytokines, which are cell-derived mediators released during the host immune response to stress, affect metabolic response to stress during critical illness. The aim of this prospective study was to determine whether the metabolic response to stress is related to the inflammatory interleukin-6 (IL-6), 10 (IL-10), and other stress mediators' responses and to assess their relationships with different feeding patterns, nutritional markers, the severity of illness as assessed by the Multiple Organ System Failure (MOSF), the Pediatric Risk of Mortality Score (PRISM), systemic inflammatory response syndrome (SIRS), and mortality in critically ill children. Patients were classified as hypermetabolic, normometabolic, and hypometabolic when the measured resting energy expenditures (REE) were >110%, 90–110% and, <90% of the predicted basal metabolic rate, respectively. The initial predominance of the hypometabolic pattern (48.6%) declined within 1 week of acute stress (20%), and the hypermetabolic patterns dominated only after 2 weeks (60%). Only oxygen consumption (VO2) and carbon dioxide production (VCO2) (P < .0001) but none of the cytokines and nutritional markers, were independently associated with a hypometabolic pattern. REE correlated with the IL-10 but not PRISM. In the presence of SIRS or sepsis, CRP, IL-6, IL-10, Prognostic Inflammatory and Nutritional Index (NI), and triglycerides—but not glucose, VO2, or VCO2 increased significantly. High IL-10 levels (P = .0000) and low measured REE (P = .0000) were independently associated with mortality (11.7%), which was higher in the hypometabolic compared to other metabolic patterns (P < .005). Our results showed that only VO2 and VCO2, but not IL-6 or IL-10, were associated with a hypometabolic pattern which predominated the acute phase of stress, and was associated with increased mortality. Although in SIRS or sepsis, the cytokine response was reliably reflected by increases in NI and

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EPA Pesticide Factsheets

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Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody.

PubMed

Fallon, Jonathan K; Vandeveer, Amanda J; Schlom, Jeffrey; Greiner, John W

2017-03-28

The combined therapeutic potential of an immunocytokine designed to deliver IL-12 to the necrotic regions of solid tumors with an anti-PD-L1 antibody that disrupts the immunosuppressive PD-1/PD-L1 axis yielded a combinatorial benefit in multiple murine tumor models. The murine version of the immunocytokine, NHS-muIL12, consists of an antibody (NHS76) recognizing DNA/DNA-histone complexes, fused with two molecules of murine IL-12 (NHS-muIL12). By its recognition of exposed DNA, NHS-muIL12 targets IL-12 to the necrotic portions of tumors; it has a longer plasma half-life and better antitumor efficacy against murine tumors than recombinant murine IL-12. It is shown here that NHS-muIL12, in an IFN-γ‒dependent mechanism, upregulates mPD-L1 expression on mouse tumors, which could be construed as an immunosuppressive action. Yet concurrent therapy with NHS-muIL12 and an anti-PD-L1 antibody resulted in additive/synergistic antitumor effects in PD-L1‒expressing subcutaneously transplanted tumors (MC38, MB49) and in an intravesical bladder tumor model (MB49). Antitumor efficacy correlated with (a) with a higher frequency of tumor antigen-specific splenic CD8+ T cells and (b) enhanced T cell activation over a wide range of NHS-muIL12 concentrations. These findings suggest that combining NHS-muIL12 and an anti-PD-L1 antibody enhances T cell activation and T cell effector functions within the tumor microenvironment, significantly improving overall tumor regression. These results should provide the rationale to examine the combination of these agents in clinical studies.

U.S. EPA, Pesticide Product Label, SPARKLE EMULSION BOWL CLEANER, 02/26/1970

EPA Pesticide Factsheets

2011-04-14

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Cytokines in chronically critically ill patients after activity and rest.

PubMed

Winkelman, Chris; Higgins, Patricia A; Chen, Yea Jyh Kathy; Levine, Alan D

2007-04-01

Inflammation, a common problem for patients in the intensive care unit (ICU), frequently is associated with serious and prolonged critical illnesses. To date, no study has examined whether physical activity influences inflammatory factors in critically ill adults. The objectives of this study were to (a) examine the relationships between type and duration of physical activity and serum levels of interleukin 6 (IL-6), a proinflammatory cytokine; IL-10, an anti-inflammatory cytokine; and their ratio and (b) determine if there are associations between cytokines or their ratio and activity or outcomes. This descriptive feasibility study investigated the approaches to measuring levels of physical activity and its relationship to serum levels of IL-6 and IL-10 and the ratio between them in patients with prolonged mechanical ventilation during periods of activity and rest. Measurements included serum IL-6 and IL-10 levels, direct observation and actigraphy, and prospective chart review. Ten critically ill patients who were mechanically ventilated for an average of 10 days in a large, urban, teaching hospital were enrolled. The average ratio of IL-6 to IL-10 improved after an average of 14.7 min of passive physical activity, typically multiple in-bed turns associated with hygiene. IL-6, IL-10, and their ratio were not associated with patient outcomes of weaning success or length of stay. High levels of IL-6 were associated with mortality. Cytokine balance may be improved by low levels of activity among patients with prolonged critical illness. The pattern of cytokines produced after activity may improve patients' recovery from prolonged critical illness and mechanical ventilation.

Buthionine sulfoximine, a glutathione depletor, attenuates endotoxic fever and reduces IL-1β and IL-6 level in rats.

PubMed

Wrotek, Sylwia; Domagalski, Krzysztof; Jędrzejewski, Tomasz; Dec, Eliza; Kozak, Wiesław

2017-02-01

The aim of our study was to investigate the effect of buthionine sulfoximine (BSO) - a glutathione depletor - on a course of endotoxic fever and IL-1β and IL-6 production. Male Wistar rats were subjected to intraperitoneal injection of lipopolysaccharide (LPS) from E. coli (50μg/kg, ip) to provoke fever. The level of spleen glutathione, plasma interleukin (IL)-1β, IL-6, and deep body temperature (Tb) were measured. The LPS administration provoked fever (the average Tb was 38.14±0.05°C in NaCl/LPS-treated rats vs 37.10±0.03°C in control, not-treated rats; p<0.001). We observed that LPS injection induced a decrease in spleen glutathione level (7.67±0.92nM/g vs 13.27±0.47nM/g in not-treated rats; p<0.001). Furthermore, the injection of LPS provoked an elevation of plasma IL-1β and IL-6 concentration (from values below the lowest detectable standard in not-treated animals to 199.99±34.89pg/mL and 7500±542.21pg/mL, respectively; p<0.001). Pretreatment with BSO enhanced glutathione decrease in LPS-treated rats (5.05±0.49nM/g), and significantly affected fever (maximal Tb was 37.81±0.07°C in BSO/LPS-treated rats vs 38.76±0.11°C in NaCl/LPS-treated rats). BSO 4h after LPS injection decreased IL-1β and IL-6 gene expression (about 1.5 fold, and 2 fold, respectively). In a consequence we observed a decrease in plasma IL-6 concentration (4h after LPS injection plasma IL-6 was 4167.17±956.54pg/mL in BSO/LPS-treated rats vs 7500±542.21pg/mL in NaCl/LPS-treated rats; p<0.001), and later IL-1β (7h after LPS injection the IL-1β concentration was not detected). Based on these data, we conclude that BSO, in addition to well-known application as an inhibitor of glutathione synthesis, is an antipyretic agent which reduces both IL-1β and IL-6 concentration. Copyright © 2016 Elsevier Ltd. All rights reserved.

The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection.

PubMed

Wei, Xu-Hong; Na, Xiao-Dong; Liao, Guang-Jie; Chen, Qiu-Ying; Cui, Yu; Chen, Feng-Ying; Li, Yong-Yong; Zang, Ying; Liu, Xian-Guo

2013-03-01

Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6. Copyright © 2012 Elsevier Inc. All rights reserved.

IL27 controls skin tumorigenesis via accumulation of ETAR-positive CD11b cells in the pre-malignant skin

PubMed Central

Dibra, Denada; Mitra, Abhisek; Newman, Melissa; Xia, Xueqing; Keenan, Camille; Cutrera, Jeffry J.; Mathis, J. Michael; Wang, Xiao-Jing; Myers, Jeffrey; Li, Shulin

2016-01-01

Establishment of a permissive pre-malignant niche in concert with mutant stem are key triggers to initiate skin carcinogenesis. An understudied area of research is finding upstream regulators of both these triggers. IL27, a pleiotropic cytokine with both pro- and anti-inflammatory properties, was found to be a key regulator of both. Two step skin carcinogenesis model and K15-KRASG12D mouse model were used to understand the role of IL27 in skin tumors. CD11b−/− mice and small-molecule of ETAR signaling (ZD4054) inhibitor were used in vivo to understand mechanistically how IL27 promotes skin carcinogenesis. Interestingly, using in vivo studies, IL27 promoted papilloma incidence primarily through IL27 signaling in bone-marrow derived cells. Mechanistically, IL27 initiated the establishment of the pre-malignant niche and expansion of mutated stem cells in K15-KRASG12D mouse model by driving the accumulation of Endothelin A receptor (ETAR)-positive CD11b cells in the skin—a novel category of pro-tumor inflammatory identified in this study. These findings are clinically relevant, as the number of IL27RA-positive cells in the stroma is highly related to tumor de-differentiation in patients with squamous cell carcinomas. PMID:27738312

[Construction, expression and immunogenicity study of a chimeric MS/hIL-12 eukaryotic expression plasmid].

PubMed

Li, Hui; Li, Rong; Zhong, Sen; Ren, Hong; Deng, Cun-liang; Shi, Xiao-ling; Wang, Ming-yong

2006-04-01

To construct and express a chimeric Mtb8.4 with signal peptide (MS)/hIL12 eukaryotic expression plasmid, and to study the immunogenicity of the MS/hIL-12 chimeric genetic vaccines. The MS/hIL-12 chimeric gene was amplified by polymerase chain reaction (PCR) and cloned into the eukaryotic expression vector pCI-neo. The correct pCI-neo-MS/hIL12 (pMSI) recombinant plasmid was identified by PCR, restricted enzyme digestion and DNA sequencing. COS-7 cells were transfected with pMSI constructs by cationic liposome. After 48 hours, mRNA of the target gene was detected by RT-PCR, and hIL-12 protein in culture supernatant and cell lysates was detected by Western blot. C57BL/6N mice were vaccinated with MS/hIL-12 chimeric gene vaccine for three times at 3 week intervals. Four weeks after the final inoculation, three mice were sacrificed for measurement of the cytokine response and cytotoxic T lymphocyte (CTL) induction. The accuracy of plasmid construction was confirmed by a number of molecular biological techniques. Transfection of COS-7 cells with plasmids pMSI lead to transient expression of fusion proteins. The IFN-gamma and IL-2 titers were (1,521 +/- 48) ng/L and (755 +/- 41) ng/L in MS/hIL-12 chimeric gene vaccine group, (820 +/- 50) ng/L and (297 +/- 31) ng/L in MS gene vaccine group, (1,487 +/- 40) ng/L and (767 +/- 50) ng/L in BCG group, (121 +/- 16) ng/L and (62 +/- 10) ng/L in vacant vector group, and (48 +/- 16) ng/L and (32 +/- 17) ng/L in PBS group respectively. The levels of IFN-gamma and IL-2 in MS/hIL-12 chimeric gene vaccine group were higher than those of MS gene vaccine group, vacant vector group and PBS group (P < 0.01) and was similar to the BCG group (P > 0.05). The level of IL-4 in BCG group [(91 +/- 11) ng/L] increased significantly as compared to other groups (P < 0.01). When effector-cell-to-target-cell ratio (E:T ratio) were 100:1, 50:1, and 10:1 respectively, the CTL activity was 77.5%, 51.2%, 30.3% in MS/hIL-12 chimeric gene vaccine group, 56

Vitamin D and Weight Cycling: Impact on Injury, Illness, and Inflammation in Collegiate Wrestlers

PubMed Central

Barcal, Jacqueline N.; Thomas, Joi T.; Hollis, Bruce W.; Austin, Kathy J.; Alexander, Brenda M.; Larson-Meyer, D. Enette

2016-01-01

This study explored the link between vitamin D status and frequency of skin infections, inflammation, and injury in college wrestlers during an academic year. Methods: Serum 25-hydroxyvitamin D (25(OH)D) (n = 19), plasma cytokine (TNF-α, IL-6, IL-10) (n = 18) concentrations, and body weight/composition were measured and injury/illness/skin infection data were collected in fall, winter, and spring. Results: In the fall, 74% of wrestlers had vitamin D concentrations <32 ng/mL which increased to 94% in winter and spring. Wrestlers lost an average of 3.4 ± 3.9 kg (p < 0.001) during the season with corresponding decreases in fat mass and increases in lean mass (p < 0.01). An inverse association between 25(OH)D concentrations and total body mass and body fat percentage was observed at all-time points (p < 0.01). Concentrations of cytokines were highly variable among individuals and did not change across time (p > 0.05). Correlations between vitamin D status, cytokines, or frequency of illness, injury, or skin infections were not observed. Conclusions: A high prevalence of vitamin D insufficiency (<32 ng/mL) and deficiency (<20 ng/mL) was observed in wrestlers and was associated with higher adiposity. It remains unclear if higher vitamin D status would reduce injury, illness, and skin infection risk. PMID:27916879

Protease activity of Per a 10 potentiates Th2 polarization by increasing IL-23 and OX40L.

PubMed

Agrawal, Komal; Kale, Sagar L; Arora, Naveen

2015-12-01

Proteases are implicated in exacerbation of allergic diseases. In this study, the role of proteolytic activity of Per a 10 was evaluated on Th2 polarization. Intranasal administration of Per a 10 in mice led to allergic airway inflammation as seen by higher IgE levels, cellular infiltration, IL-17A, and Th2 cytokines, whereas, inactive (Δ)Per a 10 showed attenuated response. There was an increased OX40L expression on lung and lymph node dendritic cells in Per a 10 immunized group and on Per a 10 stimulated BMDCs. Reduction in CD40 expression without any change at transcript level in lungs of Per a 10 immunized mice suggested CD40 cleavage. BMDCs pulsed with Per a 10 showed reduced CD40 expression with lower IL-12p70 secretion as compared to heat inactivated Per a 10. IL-23, TNF-α, and IL-6 levels were significantly higher in Per a 10 stimulated BMDCs supernatant. In DC-T cell coculture studies, Per a 10 pulsed BMDCs showed higher levels of IL-4 and IL-13 that were reduced on blocking of either IL-23 or OX40L. In conclusion, the data suggests a critical role of protease activity of Per a 10 in promoting Th2 polarization by increasing IL-23 secretion and OX40L expression on dendritic cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

PubMed

Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Wilkosc, Monika; Frydecka, Dorota; Groszewska, Agata; Narozna, Beata; Dmitrzak-Weglarz, Monika; Czerski, Piotr; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Leszczynska-Rodziewicz, Anna; Slopien, Agnieszka; Zaremba, Dorota; Twarowska-Hauser, Joanna

2015-12-01

Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed. Copyright © 2015 Elsevier B.V. All rights reserved.

U.S. EPA, Pesticide Product Label, 2, NITRO-2-ETHYL-1, 3-PROPANEDIOL, 03/19/1969

EPA Pesticide Factsheets

2011-04-13

... ( 1,1,') c.;. II v ,> U .... · 1 jul ey , '. ,J • I'll L 1'1Il i, 'iiJG, SIP, • (lS) J. L. Ril~U:~UIliL't', J. Ot'g. CI,,·iil. g, lH2-U:i'1 (L'j'iu). (L7) V 1 •• 1 . • lJ.:->. J 1 I r <;. ...

Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis.

PubMed

Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2008-04-01

Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage.

IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer.

PubMed

Mace, Thomas A; Shakya, Reena; Pitarresi, Jason R; Swanson, Benjamin; McQuinn, Christopher W; Loftus, Shannon; Nordquist, Emily; Cruz-Monserrate, Zobeida; Yu, Lianbo; Young, Gregory; Zhong, Xiaoling; Zimmers, Teresa A; Ostrowski, Michael C; Ludwig, Thomas; Bloomston, Mark; Bekaii-Saab, Tanios; Lesinski, Gregory B

2018-02-01

Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively. In vivo efficacy and mechanistic studies were conducted with antibodies (Abs) targeting IL-6, PD-L1, CD4 or CD8 in subcutaneous or orthotopic models using Panc02, MT5 or KPC-luc cell lines; and the aggressive, genetically engineered PDAC model (Kras LSL-G12D , Trp53 LSL-R270H , Pdx1-cre, Brca2 F/F (KPC-Brca2 mice)). Systemic and local changes in immunophenotype were measured by flow cytometry or immunohistochemical analysis. PSCs (n=12) demonstrated prominent IL-6 expression, which was localised to stroma of tumours. Combined IL-6 and PD-L1 blockade elicited efficacy in mice bearing subcutaneous MT5 (p<0.02) and Panc02 tumours (p=0.046), which was accompanied by increased intratumoural effector T lymphocytes (CD62L - CD44 - ). CD8-depleting but not CD4-depleting Abs abrogated the efficacy of combined IL-6 and PD-L1 blockade in mice bearing Panc02 tumours (p=0.0016). This treatment combination also elicited significant antitumour activity in mice bearing orthotopic KPC-luc tumours and limited tumour progression in KPC-Brca2 mice (p<0.001). Histological analysis revealed increased T-cell infiltration and reduced α-smooth muscle actin cells in tumours from multiple models. Finally, IL-6 and PD-L1 blockade increased overall survival in KPC-Brca2 mice compared with isotype controls (p=0.0012). These preclinical results indicate that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in PDAC. Published by the BMJ Publishing Group Limited. For

U.S. EPA, Pesticide Product Label, , 11/23/1966

EPA Pesticide Factsheets

2011-04-14

... r ~ ~,1]l~ ~ ~{Ql1! !IINK( I ~~~.~itt~~~I~~ 11 l ~~~~~ t· --' L . . ~_".... ___ . __ . ..--J ' . • t ) IL " t~S .. 50· Formulating Information! ...

IL-17A induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth muscle cells: role of MAPK (Erk1/2, JNK, and p38) pathways.

PubMed

Rahman, Muhammad Shahidur; Yamasaki, Akira; Yang, Jie; Shan, Lianyu; Halayko, Andrew J; Gounni, Abdelilah Soussi

2006-09-15

Recently, IL-17A has been shown to be expressed in higher levels in respiratory secretions from asthmatics and correlated with airway hyperresponsiveness. Although these studies raise the possibility that IL-17A may influence allergic disease, the mechanisms remain unknown. In this study, we investigated the molecular mechanisms involved in IL-17A-mediated CC chemokine (eotaxin-1/CCL11) production from human airway smooth muscle (ASM) cells. We found that incubation of human ASM cells with rIL-17A resulted in a significant increase of eotaxin-1/CCL11 release from ASM cells that was reduced by neutralizing anti-IL-17A mAb. Moreover, IL-17A significantly induced eotaxin-1/CCL11 release and mRNA expression, an effect that was abrogated with cycloheximide and actinomycin D treatment. Furthermore, transfection studies using a luciferase-driven reporter construct containing eotaxin-1/CCL11 proximal promoter showed that IL-17A induced eotaxin-1/CCL11 at the transcriptional level. IL-17A also enhanced significantly IL-1beta-mediated eotaxin-1/CCL11 mRNA, protein release, and promoter activity in ASM cells. Primary human ASM cells pretreated with inhibitors of MAPK p38, p42/p44 ERK, JNK, or JAK but not PI3K, showed a significant decrease in eotaxin-1/CCL11 release upon IL-17A treatment. In addition, IL-17A mediated rapid phosphorylation of MAPK (p38, JNK, and p42/44 ERK) and STAT-3 but not STAT-6 or STAT-5 in ASM cells. Taken together, our data provide the first evidence of IL-17A-induced eotaxin-1/CCL11 expression in ASM cells via MAPK (p38, p42/p44 ERK, JNK) signaling pathways. Our results raise the possibility that IL-17A may play a role in allergic asthma by inducing eotaxin-1/CCL11 production.

IL8 and IL16 levels indicate serum and plasma quality.

PubMed

Kofanova, Olga; Henry, Estelle; Quesada, Rocio Aguilar; Bulla, Alexandre; Linares, Hector Navarro; Lescuyer, Pierre; Shea, Kathi; Stone, Mars; Tybring, Gunnel; Bellora, Camille; Betsou, Fay

2018-02-09

Longer pre-centrifugation times alter the quality of serum and plasma samples. Markers for such delays in sample processing and hence for the sample quality, have been identified. Twenty cytokines in serum, EDTA plasma and citrate plasma samples were screened for changes in concentration induced by extended blood pre-centrifugation delays at room temperature. The two cytokines that showed the largest changes were further validated for their "diagnostic performance" in identifying serum or plasma samples with extended pre-centrifugation times. In this study, using R&D Systems ELISA kits, EDTA plasma samples and serum samples with a pre-centrifugation delay longer than 24 h had an IL16 concentration higher than 313 pg/mL, and an IL8 concentration higher than 125 pg/mL, respectively. EDTA plasma samples with a pre-centrifugation delay longer than 48 h had an IL16 concentration higher than 897 pg/mL, citrate plasma samples had an IL8 concentration higher than 21.5 pg/mL and serum samples had an IL8 concentration higher than 528 pg/mL. These robust and accurate tools, based on simple and commercially available ELISA assays can greatly facilitate qualification of serum and plasma legacy collections with undocumented pre-analytics.

Identification of active compounds from Caesalpinia sappan L. extracts suppressing IL-6 production in RAW 264.7 cells by PLS.

PubMed

Chu, Ming-Juan; Wang, You-Zhi; Itagaki, Kiyoshi; Ma, Hong-Xing; Xin, Ping; Zhou, Xue-Gang; Chen, Guo-You; Li, Sen; Sun, Shi-Qin

2013-06-21

Caesalpinia sappan L. is distributed in Southeast Asia and also used as herbal medicine for the treatment of various diseases such as burning sensations, leprosy, dysentery, osteoarthritis and rheumatoid arthritis (RA). The overproduction of IL-6 plays an important role in the prognosis of RA, but the active compounds from the extracts of Caesalpinia sappan L. suppressing IL-6 production remain unknown. Identifying the main active compounds of Caesalpinia sappan L. extracts inhibiting the IL-6 production in LPS-stimulated RAW 264.7 cells by partial least squares (PLS). Sixty-four samples with different proportions of compounds were prepared from Caesalpinia sappan L. by supercritical CO2 fluid extraction (SCFE) and refluxing. Each of 64 samples was applied to RAW 264.7 cells with LPS to evaluate whether IL-6 production by LPS is affected by addition of each sample. The IL-6 production in medium was determined by ELISA and the inhibitory activity of each sample was analyzed. In addition, the fingerprints of these 64 samples were also established by ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-MS). We used the PLS, a simplified method, to evaluate the results from IL-6 production and fingerprints. Each of 64 samples markedly suppressed LPS-induced IL-6 production in RAW cells. The fingerprints by UPLC-MS clearly revealed variations among 64 samples produced in different extract conditions. The PLS analysis with IL-6 production and fingerprints by UPLC-MS suggested that the peaks 71, 93, 150, 157, 168 have more influence on the inhibitory activity of Caesalpinia sappan L. extracts. The peaks 71, 93, 150 are likely representing sappanone A, protosappanin E and neoprotosappanin, respectively. The peaks 157 and 168 are still at large. This is the first report that sappanone A, protosappanin E, neoprotosappanin and two unidentified compounds can be considered as possible active compounds that might inhibit IL-6 production

78 FR 44524 - In the Matter of: Orville L. Parker, Jr., 2647 W. Walton Street, Chicago, IL 60622, Respondent...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

...., 2647 W. Walton Street, Chicago, IL 60622, Respondent; Order Relating to Orville L. Parker, Jr. The... this Order, Orville L. Parker, Jr., with a last known address of 2647 W. Walton Street, Chicago, IL... 9, 2013. David W. Mills, Assistant Secretary of Commerce for Export Enforcement. [FR Doc. 2013-17824...

A prospective randomised trial of probiotics in critically ill patients.

PubMed

McNaught, Clare E; Woodcock, Nicholas P; Anderson, Alexander D G; MacFie, John

2005-04-01

Probiotics exert a beneficial effect on the host through modulation of gastrointestinal microflora. The aim of this study was to investigate the effect of the probiotic Lactobacillus plantarum 299v on gut barrier function and the systemic inflammatory response in critically ill patients. One hundred and three critically ill patients were randomised to receive an oral preparation containing L. plantarum 299v (ProViva) in addition to conventional therapy (treatment group, n = 52) or conventional therapy alone (control group, n = 51). Serial outcome measures included gastric colonisation, intestinal permeability (lactulose/rhamnose dual-sugar probe technique), endotoxin exposure (IgM EndoCAb), C-reactive protein and Interleukin 6 levels. L. plantarum had no identifiable effect on gastric colonisation, intestinal permeability, endotoxin exposure or serum CRP levels. There were no differences between the groups in terms of septic morbidity or mortality. On day 15 serum IL-6 levels were significantly lower in the treatment group compared to controls. The enteral administration of L. plantarum 299v to critically ill patients was associated with a late attenuation of the systemic inflammatory response. This was not accompanied by any significant changes in the intestinal microflora, intestinal permeability, endotoxin exposure, septic morbidity or mortality.

Systemic inflammation after critical illness: relationship with physical recovery and exploration of potential mechanisms.

PubMed

Griffith, David M; Lewis, Steff; Rossi, Adriano G; Rennie, Jillian; Salisbury, Lisa; Merriweather, Judith L; Templeton, Kate; Walsh, Timothy S

2016-09-01

Physical recovery following critical illness is slow, often incomplete and is resistant to rehabilitation interventions. We aimed to explore the contribution of persisting inflammation to recovery, and investigated the potential role of human cytomegalovirus (HCMV) infection in its pathogenesis. In an a priori nested inflammatory biomarker study in a post-intensive care unit (ICU) rehabilitation trial (RECOVER; ISRCTN09412438), surviving adult ICU patients ventilated >48 h were enrolled at ICU discharge and blood sampled at ICU discharge (n=184) and 3 month follow-up (N=123). C-reactive protein (CRP), human neutrophil elastase (HNE), interleukin (IL)-1β, IL-6, IL-8, transforming growth factor β1 (TGFβ1) and secretory leucocyte protease inhibitor (SLPI) were measured. HCMV IgG status was determined (previous exposure), and DNA PCR measured among seropositive patients (lytic infection). Physical outcome measures including the Rivermead Mobility Index (RMI) were measured at 3 months. Many patients had persisting inflammation at 3 months (CRP >3 mg/L in 59%; >10 mg/L in 28%), with proinflammatory phenotype (elevated HNE, IL-6, IL-8, SLPI; low TGFβ1). Poorer mobility (RMI) was associated with higher CRP (β=0.13; p<0.01) and HNE (β=0.32; p=0.03), even after adjustment for severity of acute illness and pre-existing co-morbidity (CRP β=0.14; p<0.01; HNE β=0.30; p=0.04). Patients seropositive for HCMV at ICU discharge (63%) had a more proinflammatory phenotype at 3 months than seronegative patients, despite undetectable HMCV by PCR testing. Inflammation is prevalent after critical illness and is associated with poor physical recovery during the first 3 months post-ICU discharge. Previous HCMV exposure is associated with a proinflammatory phenotype despite the absence of detectable systemic viraemia. ISRCTN09412438, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

U.S. EPA, Pesticide Product Label, , 06/21/1976

EPA Pesticide Factsheets

2011-04-19

... If ,;w1<,\\\\,1, ,i!'lIlK I'H( ).\\11' I LY. a LIn,· 1.jU:llil'ty "I' !lltlk, "J.!:g whitt'S, gPlatlt1 solution. or if thl'>;" an' 'wt j\\:td;tl'I,', dril,k !:ll'l,!t' 'Ill.llltlt]., "f \\\\:tt. ...

ATG16L1 and IL23R are associated with inflammatory bowel diseases but not with celiac disease in the Netherlands.

PubMed

Weersma, Rinse K; Zhernakova, Alexandra; Nolte, Ilja M; Lefebvre, Céline; Rioux, John D; Mulder, Flip; van Dullemen, Hendrik M; Kleibeuker, Jan H; Wijmenga, Cisca; Dijkstra, Gerard

2008-03-01

Inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--and celiac disease are intestinal inflammatory disorders with a complex genetic background. Recently, two novel genes were found to be associated with IBD susceptibility. One, an uncommon coding variant (rs11209026) in the gene encoding for the interleukin-23 receptor (IL23R), conferred strong protection against CD. The other, rs2241880 in the autophagy-related 16-like 1 gene (ATG16L1), was associated with CD. We performed a case-control study for the association of IBD with IL23R and ATG16L1 in a Dutch cohort. We also looked at the association of IL23R and ATG16L1 with celiac disease. Five hundred eighteen Dutch white IBD patients (311 CD and 207 UC, including 176 trios of patients with both parents), 508 celiac disease patients, and 893 healthy controls were studied for association with the rs11209026 (IL23R) and rs2241880 (ATG16L1) single nucleotide polymorphisms (SNP). The rs11209026 SNP in IL23R had a protective effect for IBD in the case-control analysis (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.10-0.37, P= 6.6E-09). Both CD (OR 0.14, CI 0.06-0.37, P= 3.9E-07) and UC (OR 0.33, CI 0.15-0.73, P= 1.4E-03) were associated with IL23R. For ATG16L1, the rs2241880 SNP was associated with CD susceptibility (OR 1.36, CI 1.12-1.66, P= 0.0017). The population-attributable risk of carrying allele G is 0.24 and is 0.19 for homozygosity for allele G in CD. No association was found between IL23R or ATG16L1 and celiac disease. We confirmed the association of IL23R and ATG16L1 with CD susceptibility and also the association of IL23R with UC. We found IL23R and ATG16L1 were not associated with celiac disease susceptibility.

Increased IL-35 producing Tregs and CD19+IL-35+ cells are associated with disease progression in leprosy patients.

PubMed

Tarique, Mohd; Saini, Chaman; Naqvi, Raza Ali; Khanna, Neena; Rao, D N

2017-03-01

The clinical forms of leprosy consist of a spectrum that reflects the host's immune response to the M. leprae; it provides an ideal model to study the host pathogen interaction and immunological dysregulation in humans. IL-10 and TGF-β producing Tregs are high in leprosy patients and responsible for immune suppression and M. leprae specific T cells anergy. In leprosy, involvement of IL-35 producing Tregs and Bregs remain unstudied. To study the role of IL-35 producing Tregs and Bregs in the human leprosy. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA) for 48h. Intracellular cytokine IL-35 was evaluated in CD4 + CD25 + Tregs, CD19 + cells by FACS. Expression of PD-1 on CD4 + CD25 + Tregs, CD19 + cells and its ligand (PD-L1) on B cells, CD11c cells were evaluated by flow cytometry (FACS). Serum IL-35 level was estimated by ELISA. The frequency of IL-35 producing Tregs and Bregs cells were found to be high in leprosy patients (p<0.0001) as compared to healthy controls. These cells produced suppressive cytokine IL-35 which showed positive correlation with bacteriological index (BI) and TGF-β producing Tregs, indicating its suppressive nature. We found higher expression of PD-1 on Tregs, B cell and its ligand (PD-L1) on antigen presenting cells in leprosy patients. This study point out a shift in our understanding of the immunological features that mediate and regulate the immune suppression and the disease progression in leprosy patients with a new paradigm (IL-35 producing Tregs and Bregs) that is beyond TGF-β and IL-10 producing Treg cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of BCAP-{sub L} as a negative regulator of the TLR signaling-induced production of IL-6 and IL-10 in macrophages by tyrosine phosphoproteomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsumura, Takayuki; Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480; Oyama, Masaaki

2010-09-17

Research highlights: {yields} Twenty five tyrosine-phosphorylated proteins in LPS-stimulated macrophages were determined. {yields} BCAP is a novel tyrosine-phosphorylated protein in LPS-stimulated macrophages. {yields} BCAP-{sub L} inhibits IL-6 and IL-10 production in LPS-stimulated macrophages. -- Abstract: Toll-like receptor (TLR) signaling in macrophages is essential for anti-pathogen responses such as cytokine production and antigen presentation. Although numerous reports suggest that protein tyrosine kinases (PTKs) are involved in cytokine induction in response to lipopolysaccharides (LPS; TLR4 ligand) in macrophages, the PTK-mediated signal transduction pathway has yet to be analyzed in detail. Here, we carried out a comprehensive and quantitative dynamic tyrosine phosphoproteomic analysismore » on the TLR4-mediated host defense system in RAW264.7 macrophages using stable isotope labeling by amino acids in cell culture (SILAC). We determined the temporal profiles of 25 proteins based on SILAC-encoded peptide(s). Of these, we focused on the tyrosine phosphorylation of B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) because the function of BCAP remains unknown in TLR signaling in macrophages. Furthermore, Bcap has two distinct transcripts, a full-length (Bcap-{sub L}) and an alternatively initiated or spliced (Bcap-{sub S}) mRNA, and little is known about the differential functions of the BCAP-{sub L} and BCAP-{sub S} proteins. Our study showed, for the first time, that RNAi-mediated selective depletion of BCAP-{sub L} enhanced IL-6 and IL-10 production but not TNF-{alpha} production in TLR ligand-stimulated macrophages. We propose that BCAP-{sub L} (but not BCAP-{sub S}) is a negative regulator of the TLR-mediated host defense system in macrophages.« less

34 CFR 365.11 - How is the allotment of Federal funds for State independent living (IL) services computed?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true How is the allotment of Federal funds for State independent living (IL) services computed? 365.11 Section 365.11 Education Regulations of the Offices of the... EDUCATION STATE INDEPENDENT LIVING SERVICES How Does the Secretary Make a Grant to a State? § 365.11 How is...

34 CFR 365.11 - How is the allotment of Federal funds for State independent living (IL) services computed?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false How is the allotment of Federal funds for State independent living (IL) services computed? 365.11 Section 365.11 Education Regulations of the Offices of the... EDUCATION STATE INDEPENDENT LIVING SERVICES How Does the Secretary Make a Grant to a State? § 365.11 How is...

U.S. EPA, Pesticide Product Label, DIAZINON 4 SPRAY, 10/04/1993

EPA Pesticide Factsheets

2011-04-21

... iIiHf III lill ~lflilf IIH ; Ii f ti' '11-III'n! 1]1 Ihfl JIlL III illi'l f 111"1 ,1111 III ILl Iltll! II', ~tlf II JII! ,11111 ' I'i, t $'1 it I Itit ,.11 jilt! if II! W!JIIU, JI I i II t J IL If '"' : If 5.:0 ...

TLR2/4 ligand-amplified liver inflammation promotes initiation of autoimmune hepatitis due to sustained IL-6/IL-12/IL-4/IL-25 expression.

PubMed

Chi, Gang; Feng, Xin-Xia; Ru, Ying-Xia; Xiong, Ting; Gao, Yuan; Wang, Han; Luo, Zhen-Long; Mo, Ran; Guo, Fang; He, Yong-Pei; Zhang, Gui-Mei; Tian, De-An; Feng, Zuo-Hua

2018-05-21

Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl 4 ) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4. The amplified inflammation resulted in the increase of multiple cytokines and chemokines in the liver. Among them, the sustained increase of IL-6/IL-12 resulted in the activation of STAT3 and STAT4 in hepatic CD4 + CD25 + Treg cells, thus suppressing Foxp3 gene expression to reduce the suppressive function of Treg cells in the liver, but not those in the spleen. The increase of IL-12 and the impairment of Treg function promoted Th1 response in presence of self-mimicking antigen (human CYP2D6). Intriguingly, the amplified inflammation resulted in the increase of IL-4 and IL-25 in the liver. The moderate increase of IL-4 was sufficient for cooperating with IL-25 to initiate Th2 response, but inefficient in suppressing Th1 response, favoring the initiation of autoimmune response. Consequently, either adenovirus/CYP2D6 or CCl 4 /CYP2D6 could induce the autoimmune response and AIH in the mice, leading to hepatic fibrosis. The findings in this study suggest that the amplified non-AIH inflammation in the liver could be a driving force for the initiation of autoimmune response and AIH. Copyright © 2018 Elsevier Ltd. All rights reserved.

Focal adhesion kinase-mediated activation of glycogen synthase kinase 3β regulates IL-33 receptor internalization and IL-33 signaling.

PubMed

Zhao, Jing; Wei, Jianxin; Bowser, Rachel K; Traister, Russell S; Fan, Ming-Hui; Zhao, Yutong

2015-01-15

IL-33, a relatively new member of the IL-1 cytokine family, plays a crucial role in allergic inflammation and acute lung injury. Long form ST2 (ST2L), the receptor for IL-33, is expressed on immune effector cells and lung epithelia and plays a critical role in triggering inflammation. We have previously shown that ST2L stability is regulated by the ubiquitin-proteasome system; however, its upstream internalization has not been studied. In this study, we demonstrate that glycogen synthase kinase 3β (GSK3β) regulates ST2L internalization and IL-33 signaling. IL-33 treatment induced ST2L internalization, and an effect was attenuated by inhibition or downregulation of GSK3β. GSK3β was found to interact with ST2L on serine residue 446 in response to IL-33 treatment. GSK3β binding site mutant (ST2L(S446A)) and phosphorylation site mutant (ST2L(S442A)) are resistant to IL-33-induced ST2L internalization. We also found that IL-33 activated focal adhesion kinase (FAK). Inhibition of FAK impaired IL-33-induced GSK3β activation and ST2L internalization. Furthermore, inhibition of ST2L internalization enhanced IL-33-induced cytokine release in lung epithelial cells. These results suggest that modulation of the ST2L internalization by FAK/GSK3β might serve as a unique strategy to lessen pulmonary inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

A Correlation between the Assignment of Personnel to Technical Order Validation/Verification Versus Technical Order Deficiency Forms Generated.

DTIC Science & Technology

1980-06-01

Position organization Loction 111111 NO CUAaI Pft"lTV PC@ PUVATUt. L $3 -- STT I BUSINESS REPLY MAIL _____ AM? SAM POWf N &. n = WMNINSTS L. POSTAGS WVl K...11. CONTROLLING OFF ICE NMEM AND ADDRESS 2 Department of Communication8 and Humanities - US P RIAGENCYNAMEA ADORESS(it different from Coneo5U...Sec.II, p .0-5-19]. And specifically to the point of this thesis: Without the additional manpower spaces, program acquisition support for Technical

Enhancement of natural killer activity and IFN-γ production in an IL-12-dependent manner by a Brassica rapa L.

PubMed

Yamamoto, Kana; Furuya, Kanon; Yamada, Kazuki; Takahashi, Fuka; Hamajima, Chisato; Tanaka, Sachi

2018-04-01

Certain food components possess immunomodulatory effects. The aim of this study was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa L. We demonstrated an enhancement of natural killer (NK) activity and interferon (IFN)-γ production in mice that were orally administered an insoluble fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced IFN-γ production in mouse spleen cells in an interleukin (IL)-12-dependent manner, and NK1.1 + cells were the main cells responsible for producing IFN-γ. Additionally, the results suggested that the active compounds in the insoluble fraction were recognized by Toll-like receptor (TLR) 2, TLR4, and C-type lectin receptors on dendritic cells, and they activated signaling cascades such as MAPK, NF-κB, and Syk. These findings suggest that B. rapa L. is a potentially promising immuno-improving material, and it might be useful for preventing immunological disorders such as infections and cancers by activating innate immunity.

Pretreatment with IL-1β enhances proliferation and chondrogenic potential of synovium-derived mesenchymal stem cells.

PubMed

Matsumura, Etsuko; Tsuji, Kunikazu; Komori, Keiichiro; Koga, Hideyuki; Sekiya, Ichiro; Muneta, Takeshi

2017-02-01

Synovial mesenchymal stem cells (MSCs) are an attractive cell source for cartilage regeneration because of their high proliferative ability and chondrogenic potential. We have performed clinical trials using synovial MSCs to regenerate articular cartilage. To achieve good clinical outcomes for cell transplantation therapy, it is important to control both quantity (cell number) and quality (pluripotency or chondrogenic potential) of the cells for transplantation. Interleukin (IL)-1β is a pro-inflammatory cytokine with significant pro-proliferative potential for mesenchymal cells. However, the effects of IL-1β on synovial MSCs remain unknown. We investigated the effects of pretreatment with IL-1β on synovial MSCs. Human synovial tissue was harvested during total knee arthroplasty. Nucleated cells were plated and cultured in the absence or presence of IL-1β at 10 -13 , 10 -12 , 10 -11 , 10 -10 , 10 -9 or 10 -8  g/mL for 14 days. The number of synovial MSCs increased in a concentration-dependent manner. When cultured for 21 days in chondrogenic medium after pretreatment with 10 -8   g/mL IL-1β, pellet aggregation was observed, whereas pretreatment with 10 -12 , 10 -11 or 10 -10  g/mL IL-1β significantly increased the weight of cartilage pellets (P <0.01). Surface markers for adhesion ability and pluripotency were reduced with high concentrations of IL-1β. IL-6 and IL-8 expression increased, but no changes in the expression level of growth factors were indicated by cytokine array. We have demonstrated that pretreatment of IL-1β increased the proliferation and chondrogenic potential of synovial MSCs, which may promote the regenerative potential of synovial MSCs. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance.

PubMed

Shiokawa, Aya; Tanabe, Kosuke; Tsuji, Noriko M; Sato, Ryuichiro; Hachimura, Satoshi

2009-06-30

Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.

Decreased serum levels of sCD40L and IL-31 correlate in treated patients with Relapsing-Remitting Multiple Sclerosis.

PubMed

de J Guerrero-García, José; Rojas-Mayorquín, Argelia E; Valle, Yeminia; Padilla-Gutiérrez, Jorge R; Castañeda-Moreno, Víctor A; Mireles-Ramírez, Mario A; Muñoz-Valle, José F; Ortuño-Sahagún, Daniel

2018-01-01

The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into account as possible prognostic markers when analyzing the disease progress of MS in order to provide more personalized treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.

Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells

PubMed Central

Krieg, Carsten; Létourneau, Sven; Pantaleo, Giuseppe; Boyman, Onur

2010-01-01

IL-2 immunotherapy is an attractive treatment option for certain metastatic cancers. However, administration of IL-2 to patients can lead, by ill-defined mechanisms, to toxic adverse effects including severe pulmonary edema. Here, we show that IL-2–induced pulmonary edema is caused by direct interaction of IL-2 with functional IL-2 receptors (IL-2R) on lung endothelial cells in vivo. Treatment of mice with high-dose IL-2 led to efficient expansion of effector immune cells expressing high levels of IL-2Rβγ, including CD8+ T cells and natural killer cells, which resulted in a considerable antitumor response against s.c. and pulmonary B16 melanoma nodules. However, high-dose IL-2 treatment also affected immune cell lineage marker-negative CD31+ pulmonary endothelial cells via binding to functional αβγ IL-2Rs, expressed at low to intermediate levels on these cells, thus causing pulmonary edema. Notably, IL-2–mediated pulmonary edema was abrogated by a blocking antibody to IL-2Rα (CD25), genetic disruption of CD25, or the use of IL-2Rβγ–directed IL-2/anti-IL-2 antibody complexes, thereby interfering with IL-2 binding to IL-2Rαβγ+ pulmonary endothelial cells. Moreover, IL-2/anti-IL-2 antibody complexes led to vigorous activation of IL-2Rβγ+ effector immune cells, which generated a dramatic antitumor response. Thus, IL-2/anti-IL-2 antibody complexes might improve current strategies of IL-2–based tumor immunotherapy. PMID:20547866

Modeling of Instrument Landing System (ILS) localizer signal on runway 25L at Los Angeles International Airport

NASA Technical Reports Server (NTRS)

Hueschen, Richard M.; Knox, Charles E.

1994-01-01

A joint NASA/FAA flight test has been made to record instrument landing system (ILS) localizer receiver signals for use in mathematically modeling the ILS localizer for future simulation studies and airplane flight tracking tasks. The flight test was conducted on a portion of the ILS localizer installed on runway 25L at the Los Angeles International Airport. The tests covered the range from 10 to 32 n.mi. from the localizer antenna. Precision radar tracking information was compared with the recorded localizer deviation data. Data analysis showed that the ILS signal centerline was offset to the left of runway centerline by 0.071 degrees and that no significant bends existed on the localizer beam. Suggested simulation models for the ILS localizer are formed from a statistical analysis.

Maternal serum but not breast milk IL-5, IL-6, and IL-13 immune markers are associated with scratching among infants.

PubMed

Soto-Ramírez, Nelís; Boyd, Keith; Zhang, Hongmei; Gangur, Venugopal; Goetzl, Laura; Karmaus, Wilfried

2016-01-01

Scratching in infants is considered to be related to early development of eczema. Little is known about the effects of maternal immune markers on scratching among infants. The objective is to compare the risks related to maternal serum immune markers (IMs) during pregnancy and IMs in breast milk for the occurrence of scratching in infants at 6 and 12 months of age. Pregnant women were recruited in Columbia and Charleston, South Carolina. Blood (median 3 weeks prepartum) and breast milk (3 weeks postpartum) samples were collected. The concentrations of interferon (IFN)-γ, IFN gamma-induced protein 10 (IP-10) (or CXCL10), CCL11, interleukin (IL) 1β, IL-4, IL-5, IL-6, IL-8 (CXCL8), IL-10, IL-12 (p70), IL-13, transforming growth factor (TGF)-β1, and immunoglobulin (Ig) A in both maternal serum and whey were assayed using optimized immunoassays. Scratching and skin manifestations were ascertained at 6 and 12 months. Generalized estimating equations were used to estimate relative risks (RRs) of IMs for repeated measurements of scratching, considering intra-individual correlations and adjusting for confounders. Of 178 women, 161 provided blood and 115 breast milk samples. IL-1β, IL-4, IL-10, IL-12, and CCL11 in maternal serum and whey were not analyzed due to a large proportion of non-detectable values. Infants in the highest tertile of IL-6 and IL-13 in maternal serum were at higher risk of scratching (RR 1.73 and 1.84, respectively; p ≤ 0.002) compared to infants in the first tertile; similarly, infants born to mothers with high (versus low) levels of serum IL-5 were also at increased risk (RR 1.60, p = 0.002). None of the breast milk IMs studied were associated with scratching. Scratching but not doctors diagnosed eczema was associated with higher levels of maternal IL-5, IL-6, and IL-13 during pregnancy. Further investigations are necessary to determine how maternal serum IMs influence infants scratching.

[Regulation of IL-1beta and IL-8 production by mu-, delta-opiate receptors agonists in vitro].

PubMed

Geĭn, S V; Gorshkova, K G; Tendriakova, S P

2008-07-01

The beta-endorphin 10(-7-)-10(-11) M in LPS (lypopolisaccharide) presence and in spontaneous cultures promoted the IL-1beta production in mixed leukocyte fraction. LPS-induced IL-8 production in leukocyte fraction was inhibited by beta-endorphin 10(-7), 10(-11) M. The enchasing effect of beta-endorphin on IL-1beta production was not blocked by naloxone and naltrindole. The inhibitory effect of beta-endorphin on IL-8 production was blocked by naloxone and naltrindole. In mononuclear and neutrophile fractions beta-endorphin and delta-agonist DADLE enchased IL-1beta production in spontaneous and LPS-stimulating cultures, when IL-8 production inhibited beta-endorphin and delta-agonist DADLE only in LPS presence. No effect of mu-agonist DAGO were observed on IL-1beta production, whereas LPS-induced IL-8 secretion in neutrophile fraction inhibited by DAGO.

Administration of recombinant interleukin-11 improves the hemodynamic functions and decreases third space fluid loss in a porcine model of hemorrhagic shock and resuscitation.

PubMed

Honma, Kaneatsu; Koles, Nancy L; Alam, Hasan B; Rhee, Peter; Rollwagen, Florence M; Olsen, Cara; Keith, James C; Pollack, Matthew

2005-06-01

We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive sham hemorrhage (group I, sham); sham hemorrhage and 50 microg/kg rhIL-11 (group II, sham + IL-11); no drug (group III, saline); or 50 microg/kg rhIL-11 (group IV, IL-11). Blood and urine samples were obtained and analyzed at baseline, at the end of hemorrhaging, and thereafter once every hour. The pleural and peritoneal effusions were precisely quantified by using clinically accepted criteria. The mean arterial pressure (MAP) was higher postresuscitation (PR) in groups I, II, and IV (71.4 +/- 7.5 mmHg, 71.0 +/- 8.9 mmHg, and 72.9 +/- 12.3 mmHg, respectively) than in group III (59.9 +/- 10.9 mmHg), and the cardiac output of PR was higher in group IV (3.46 +/- 0.56 L/min) than in group III (2.99 +/- 0.62 L/min; P < 0.01). The difference in MAP between groups I and II became statistically significant at 40 min after rhIL-11 injection and such a difference persisted for 90 min. After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 +/- 325 mL and 1.0035, 82 +/- 21 mL) than in group III (958 +/- 390 mL and 1.0053, 125 +/- 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This

Interleukin-1 and IL-1 receptor antagonist in gingival crevicular fluid.

PubMed

Rawlinson, A; Dalati, M H; Rahman, S; Walsh, T F; Fairclough, A L

2000-10-01

This study aimed to investigate the cytokine IL-1beta and its receptor antagonist IL-1ra in gingival crevicular fluid (GCF), in patients with adult periodontitis. A total of 40 GCF samples were harvested from 10 subjects with moderate to severe adult periodontitis and 10 healthy controls. Subjects were selected from both genders, with all the upper anterior teeth present, and with no relevant systemic illness, pregnancy or recent medication. All subjects were non-smokers and had not received any periodontal therapy within the preceding 3 months. Deep bleeding sites, deep non-bleeding sites and healthy sites were investigated in relation to upper anterior teeth. Clinical measurements were recorded for each site, after obtaining a GCF sample. IL-1beta and IL-1ra were quantified using new commercially available ELISA kits (Quantikine), and could be detected in all samples. The mean concentration for IL-1beta was 0.11 (SD 0.14) pg/microl for bleeding periodontitis sites, 0.04 (0.05) pg/microl for non-bleeding periodontitis sites, and 0.01 (0.03) pg/microl for healthy sites (p<0.001). In contrast, the mean concentration for IL-1ra was 6.99 (9.78) pg/microl for healthy sites, 0.59 (0.44) pg/microl for non-bleeding periodontitis sites, and 0.44 (0.36) pg/microl for bleeding periodontitis sites (p<0.001, except for comparisons between bleeding and non-bleeding periodontitis sites, p>0.05). For healthy sites, a strong inverse relationship was found between IL-1beta and IL-1ra levels in GCE. The results suggest a strong relationship between the severity of adult periodontitis and the increasing GCF levels of IL-1beta and decreasing levels of IL-1ra.

Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8.

PubMed

Abood, Walaa Najm; Fahmi, Iman; Abdulla, Mahmood Ameen; Ismail, Salmah

2014-06-27

Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work. T. crispa ethanol extract was fractionated by using different solvents. The ethanol extract and effective isolated fraction were used to investigate the potential immunomodulatory effect of different T. crispa doses ranging from 25 μg/mL to 1000 μg/mL on RAW 246.7 cells by detecting intracellular INF-γ, IL-6, and IL-8 expressions. The antioxidant activity of T. crispa was evaluated through FRAP and DPPH. The total phenolic and total flavonoid contents were also quantified. Results show that T. crispa extract has higher antioxidant potential than ascorbic acid. The FRAP value of T. crispa extract is 11011.11 ± 1145.42 μmol Fe(+2)/g, and its DPPH inhibition percentage is 55.79 ± 7.9, with 22 μg/mL IC50. The results also reveal that the total phenolic content of T. crispa extract is 213.16- ± 1.31 mg GAE/g dry stem weight, and the total flavonoid content is 62.07- ± 39.76 mg QE/g dry stem weight. T. crispa crude extract and its isolated fraction significantly stimulate RAW264.7 cell viability (P ≤ 0.05) and intracellular INF-γ, IL-6, and IL-8 expressions. The results of LC-MS show that four of the active compounds detected in the T. crispa isolated fraction are cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine. The results of this study obviously indicate that T. crispa has immunomodulatory effects through the stimulation of INF-γ, IL-6, and IL-8 expressions. LC-MS phytochemical analysis showed that the T. crispa fraction has cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine, which may be responsible for the immunostimulator effect of T. crispa.

Sustained CD4+ T cell-driven lymphopenia without a compensatory IL-7/IL-15 response among high-grade glioma patients treated with radiation and temozolomide

PubMed Central

Ellsworth, Susannah; Balmanoukian, Ani; Kos, Ferdynand; Nirschl, Christopher J; Nirschl, Thomas R; Grossman, Stuart A; Luznik, Leo; Drake, Charles G

2014-01-01

Prolonged lymphopenia correlating with decreased survival commonly occurs among glioma patients undergoing radiation therapy (RT) and temozolomide (TMZ) treatment. To better understand the pathophysiology of this phenomenon, we prospectively monitored serum cytokine levels and lymphocyte subsets in 15 high-grade glioma patients undergoing combined radiation and TMZ (referred to as RT/TMZ) treatment. Sufficient data for analysis were acquired from 11 of the patients initially enrolled. Lymphocyte phenotyping data were obtained using cytofluorometric analysis and serum cytokine levels were measured using the a multiplex bead-based assays. Total lymphocyte counts (TLCs) were > 1000 cells per μL peripheral blood in 10/11 patients at baseline, but dropped significantly after treatment. Specifically, after RT/TMZ therapy, the TLCs were found to be < 500 cells/μL in 2/11 patients, 500–1000 cells/μL in 7/11 patients, and > 1000 cells/μL in the remaining 2 patients. Among residual mononuclear blood cells, we observed a proportional drop in B and CD4+ T cells but not in CD8+ T lymphocytes. Natural killer cells remained to near-to-baseline levels and there was a transient and slight (insignificant) increase in regulatory T cells (Tregs). The circulating levels of IL-7 and IL-15 remained low despite marked drops in both the total and CD4+ T lymphocyte counts. Thus, patients with malignant glioma undergoing RT/TMZ treatment exhibit a marked decline in TLCs, affecting both CD4+ T cells and B lymphocytes, in the absence of a compensatory increase in interleukin-7 levels. The failure to mount an appropriate homeostatic cytokine response may be responsible for the prolonged lymphopenia frequently observed in these patients. PMID:24790790

IL-1beta, IL-6 and IL-8 levels in gyneco-obstetric infections.

PubMed Central

Basso, Beatriz; Giménez, Francisco; López, Carlos

2005-01-01

OBJECTIVE: During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1beta, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy. METHODS: The selected patients were: healthy or control group (n = 52), those with bacterial vaginosis (n = 47), those with vaginitis (n = 37), those with asymptomatic urinary infection (n = 15) and post-treatment. The level of cytokines was assayed by ELISA test. The Mann-Whitney U-test was used for statistical analysis. RESULTS: The IL-1beta levels in vaginal discharge were: control 103.5 +/- 24.2 pg/ml, bacterial vaginosis 1030 +/- 59.5, vaginitis 749.14 +/- 66.7l ( p < 0.0001), post-treatment 101.4 +/- 28.7. IL-6 values were similar in both control and infected groups, and there were no patients with chorioamnionitis. In vaginal discharge IL-6: control 14.2 +/- 3.9 pg/ml, bacterial vaginosis 13.2 +/- 3.8, vaginitis 13 +/- 4.2. IL-8 levels were: control 1643 +/- 130.3 pg/ml, bacterial vaginosis 2612.7 +/- 257.7, vaginitis 3437 +/- 460 (p < 0.0001), post-treatment 1693 +/- 126.6. In urine the results were: control 40.2 +/- 17 pg/ml, asymptomatic urinary infection 1200.7 +/- 375 (p < 0.0001). In patients with therapeutic success both IL-1beta and IL-8 returned to normal levels. CONCLUSIONS: Genitourinary infections induce a significant increase in IL-1beta and IL-8 levels in vaginal secretions, and IL-8 in urine as well. Both cytokines could be useful as evolutive markers of infection. PMID:16338780

Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis.

PubMed

Lucendo, Alfredo J; De Rezende, Livia; Comas, Carmen; Caballero, Teresa; Bellón, Teresa

2008-09-01

Our aim was to evaluate the changes induced by topical steroid treatment to the esophageal epithelial inflammatory eosinophilic and T-cell infiltrate and to IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 esophageal gene expression levels in patients with eosinophilic esophagitis (EE). Esophageal biopsies were taken from eight adult patients at the moment of diagnosis and after 3-month treatment with fluticasone propionate. Eosinophils, CD8, and CD4 T cells were examined by immunohistochemistry. IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression levels were measured by real-time PCR. Eight control samples were also analyzed. A significant decrease in the eosinophil infiltrate and in CD8(+) T-cell density was observed in the esophageal epithelium from the patients upon steroid treatment. IL-5 was not detected in control samples, and expression levels were variably downregulated after treatment in six of the patients. Gene expression of eotaxin-1/CCL11 showed relevant downregulation in four cases and a modest twofold decrease in three of the patients studied. Mean CCL11 expression values upon steroid treatment were similar to control samples (19.4 +/- 28.6 vs 8.42 +/- 5, P= 0.7). Eotaxin-3/CCL26 gene expression levels were significantly increased in EE. Although they were significantly downregulated upon steroid treatment, control expression levels were not reached in any of the cases analyzed (580.9 +/- 943.9 vs 1.45 +/- 1.0, P= 0.001). Our results confirm that eotaxin-3/CCL26 is significantly increased in EE esophageal samples. However, the individual analysis of IL-5, CCL11, and CCL26 expression data suggests that several cytokines and chemokines could participate in the physiopathology of EE in humans.

U.S. EPA, Pesticide Product Label, CHEMMATE - 20S, 03/10/1983

EPA Pesticide Factsheets

2011-04-21

... h .... ;l u· .t,jlj t, J 1, .·,I'r ~" ,!I'ill '. ~" , 1" ~ll:HI~ i 11\\" I • .J hi It ,', ., I Ufo/,·th. n\\\\'d~ u"'J""!" · III:I(.:I,.I(I,il":II'. lL_nl.:II.I,J!lir~;li.d!.' .• Jl:. 'j!,f ~1.7 to ...

IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA/IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity against murine breast and colon carcinomas.

PubMed

Kim, Peter S; Kwilas, Anna R; Xu, Wenxin; Alter, Sarah; Jeng, Emily K; Wong, Hing C; Schlom, Jeffrey; Hodge, James W

2016-03-29

Interleukin (IL)-15-N72D superagonist-complexed with IL-15RαSushi-Fc fusion protein (IL-15SA/IL-15RαSu-Fc; ALT-803) has been reported to exhibit significant anti-tumor activity in murine myeloma, rat bladder cancer, and murine glioblastoma models. In this study, we examined the immunomodulatory and anti-tumor effects of IL-15SA/IL-15RαSu-Fc in tumor-free and highly metastatic tumor-bearing mice. Here, IL-15SA/IL-15RαSu-Fc significantly expanded natural killer (NK) and CD8+ T cells. In examining NK cell subsets, the greatest significant increase was in highly cytotoxic and migrating (CD11b+, CD27hi; high effector) NK cells, leading to enhanced function on a per-cell basis. CD8+ T cell subset analysis determined that IL-15SA/IL-15RαSu-Fc significantly increased IL-15 responding memory (CD122+, CD44+) CD8+ T cells, in particular those having the innate (NKG2D+, PD1-) phenotype. In 4T1 breast tumor-bearing mice, IL-15SA/IL-15RαSu-Fc induced significant anti-tumor activity against spontaneous pulmonary metastases, depending on CD8+ T and NK cells, and resulting in prolonged survival. Similar anti-tumor activity was seen in the experimental pulmonary metastasis model of CT26 colon carcinoma cells, particularly when IL-15SA/IL-15RαSu-Fc was combined with a cocktail of checkpoint inhibitors, anti-CTLA-4 and anti-PD-L1. Altogether, these studies showed for the first time that IL-15SA/IL-15RαSu-Fc (1) promoted the development of high effector NK cells and CD8+ T cell responders of the innate phenotype, (2) enhanced function of NK cells, and (3) played a vital role in reducing tumor metastasis and ultimately survival, especially in combination with checkpoint inhibitors.

Predictive value of IL-35 and IL-17 in diagnosis of childhood asthma.

PubMed

Mansour, Amira Ibrahim; Abd Almonaem, Eman Rateb; Behairy, Ola Galal; Gouda, Tahany Mahmoud

2017-09-01

This study aimed to evaluate the correlation between serum levels of IL-17 and IL-35 and the presence and severity of childhood asthma. The study was performed on 60 diagnosed asthmatic children, who were further classified into four groups according to the Global Initiative for Asthma Guidelines for Asthma Severity and Control (GINA) 2016, plus 30 age- and sex-matched apparently healthy children. All participants were subjected to full medical history, clinical examination, pulmonary function tests and laboratory evaluation in the form of complete blood count (CBC), serum total IgE, IL-17 and IL-35 by ELISA. Our results revealed that eosinophils count, IgE and IL-17 were significantly higher in the asthmatic group than the control group (p < .001), while IL-35 levels were significantly lower in asthmatics than control (p < .001). A strong negative correlation was found between serum IL-17 and serum IL-35; a positive correlation was found between serum IL-17 and both of serum total IgE and eosinophils counts in atopic asthmatic patients, and serum IL-35 showed significant negative correlations with both. ROC analysis of the data showed that the cut-off value of IL-35 level was <189.5 pg/mL and for IL-17 level, it was >13.1 pg/mL; this value could predict childhood asthma with sensitivity of 81.7% and 83.3%, and specificity of 76.7% and 70%, respectively. A combination of both cytokines yielded an increase in sensitivity to 95%. In conclusion, in the current study, IL-17 is upregulated while IL-35 is downregulated in childhood asthma with a significant negative correlation between both. These results suggest that both may play an important role in the pathogenesis of childhood asthma.

The influence of black cumin seed oil therapy with dosage of 1.5 mL/day and 3 mL/day to interleukin-21 (IL-21) expression of the patients with metabolic syndrome risk

NASA Astrophysics Data System (ADS)

Fajar, D. R.; Akrom; Darmawan, E.

2017-11-01

Metabolic syndrome (MS) is a metabolic disorder caused by obesity and insulin resistance. In the state of obesity and insulin resistance occurs increased fat metabolism that causes production reactive oxygen species (ROS) and oxidative stress that makes dysregulation of adipose tissue that decreases antioxidant enzymes and immune system disorders. In diabetes mellitus there is pancreatic β cell damage caused by pro-inflammatory cytokines i.e interleukin-21 (IL-21). Black cumin seed oil (BCSO) contains antioxidants and immunomodulators but has not seen how it affects to IL-21. This study used cross over design to determine the effect of BCSO with dose of 1.5 mL/day and 3 mL/day dose of IL-21 in MS patients. The total subjects 66 of MS patients were divided into 2 groups. Group I was administered 1.5 mL/day and 3 mL/day of BCSO in dosage for 20 days and continued with washing out (BCSO discontinued) for 7 days. On the day 28, group I administrated 3 mL/day of BCSO and group II were given 1.5 mL/day of BCSO during 20 days. Statistical analysis showed that mean value expression of IL-21 were given by BCSO at dose 1.5 mL/day was 5.06±5.48 and BCSO at dose 3 mL/day 4.66±3.63 (p<0.05). The result showed that IL-21 expression in patient at risk of MS who received BCSO dose 3 mL/day were lower than those received adose of 1.5 mL/day for 20 days.

Robustness of a Moving-Bank Multiple Model Adaptive Controller for a Large Space Structure.

DTIC Science & Technology

1989-12-01

iDecemr I) 9 S9 ’\\ hro-’’ ’ for j n hilc rch’ase; disi nilooi ci iii liiitd 1%,I t Iln lI Iu livi i II r illh t1.1 hu i ll II ] O w fi-. \\ o t I lllw t...8217 I ! l’s i l h P’tr/ il t Lnnt ill, NI-iIit INil- II’VII’il V f til Bnri N J ’, A 0.0) . .. ..- 21....1 .. I I. m’rniit I.>I Iit hIt \\lI tii A11 ;1...itii 1, iisiiiu 1’ Ni t w’ ~ iith ~ A -N - I N’\\t 3.5 .. . .. I,-, l I IIiii t i a I luIrI - %,it l h V r.I i -/I, I - J l i- I.L’ :1 1 NI uiu1;tt-tli

Antigenic characterization of intermediate adenovirus 14-11 strains associated with upper respiratory illness in a military camp.

PubMed Central

Hierholzer, J C; Pumarola, A

1976-01-01

An unusual variant of adenovirus (AV) 11 was isolated from throat and rectal swabs from six persons with upper respiratory illness in a Spanish military camp in March 1969. The same strain was serologically related to the upper respiratory illness of seven other men among 25 sample cases studied in detail. After strain purification, the virus was grouped as an AV by standard biological tests; it possessed the usual titers of group-specific hexon antigen but only low hemagglutinin titers (1:4 to 1:8) with erythrocytes from selected rhesus monkeys. The virus gave little reaction in hemagglutination inhibition (HI) tests with antisera to AV 1 through 35, but was neutralized to homologous titers by AV 11 antiserum. Reciprocally, rabbit and guinea pig antisera to the isolates possessed high HI antibody titers to prototype AV 14 and high serum neutralization (SN) antibody titers to prototype AV 11. On this basis, the variants were classified as AV 14-11 intermediates. Sequential serum specimens from the patients with and without positive cultures showed diagnostic rises in HI and SN antibody levels to the AV 14-11 intermediate and to prototype AV 11, but little response to AV 14. PMID:177365

The immune imbalance in the second hit of pancreatitis is independent of IL-17A.

PubMed

Thomson, John-Edwin; Brand, Martin; Fonteh, Pascaline

2018-04-01

Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP. Thirty-six patients with mild (n = 16), moderate (n = 10) and severe (n = 10) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for analysis of routine clinical markers as well as cytokine analysis. Flow cytometry and a IL-17A ELISA was performed to determine cytokine concentrations. There were no significant differences between days 7, 9, 11 and 13 for either the mild/moderate or SAP groups for IL-17A (CBA assay or ELISA), IFN-γ, TNF-α, IL-2 or IL-4. For each of the study days, the mean IL-6 and IL-10 concentrations were significantly higher in the SAP group compared to the mild/moderate group. WCC, CRP and PCT were all significantly higher in severe acute pancreatitis over the study days. An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Tumor Necrosis Factor-α and Interleukin (IL)-1β, IL-6, and IL-8 Impair In Vitro Migration and Induce Apoptosis of Gingival Fibroblasts and Epithelial Cells, Delaying Wound Healing.

PubMed

Basso, Fernanda G; Pansani, Taisa N; Turrioni, Ana Paula S; Soares, Diana G; de Souza Costa, Carlos Alberto; Hebling, Josimeri

2016-08-01

Multiple factors affect oral mucosal healing, such as the persistence of an inflammatory reaction. The present study evaluates effects of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6, and IL-8 on epithelial cells (ECs) and human gingival fibroblasts (GFs) in vitro. GFs and ECs were seeded in 96-well plates (1 × 10(4) cells/well) in plain culture medium (Dulbecco's modified Eagle's medium [DMEM]) containing 1% antibiotic/antimycotic solution and 10% fetal bovine serum, and incubated for 24 hours. Both cell lines were exposed for 24 hours to the following cytokines: 1) TNF-α (100 ng/mL); 2) IL-1β (1 ng/mL); 3) IL-6 (10 ng/mL); and 4) IL-8 (10 ng/mL). All cytokines were diluted in serum-free DMEM. Control cultures were exposed only to serum-free DMEM. Effects of exposure to inflammatory cytokines were determined by means of: 1) apoptosis (anexin V); 2) cell migration (wound healing assay); 3) inflammatory cytokine synthesis (enzyme-linked immunosorbent assay). Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests (α = 0.05). Increased apoptosis rates were noted when cells were exposed to inflammatory cytokines, except ECs exposed to IL-1β. Cell migration was negatively affected by all inflammatory cytokines for both cell lines. ECs and GFs exposed to IL-6 and IL-8 significantly increased synthesis of TNF-α and IL-1β. Demonstrated results indicate negative effects of tested inflammatory cytokines on ECs and GFs, inducing apoptosis and impairing cell migration. These results can justify delayed oral mucosa healing in the presence of inflammatory reaction.

IL1RN Coding Variant Is Associated with Lower Risk of Acute Respiratory Distress Syndrome and Increased Plasma IL-1 Receptor Antagonist

PubMed Central

Feng, Rui; Li, Mingyao; Zhao, Yang; Sheu, Chau-Chyun; Tejera, Paula; Gallop, Robert; Bellamy, Scarlett; Rushefski, Melanie; Lanken, Paul N.; Aplenc, Richard; O’Keefe, Grant E.; Wurfel, Mark M.; Christiani, David C.; Christie, Jason D.

2013-01-01

Rationale: Acute respiratory distress syndrome (ARDS) behaves as a complex genetic trait, yet knowledge of genetic susceptibility factors remains incomplete. Objectives: To identify genetic risk variants for ARDS using large scale genotyping. Methods: A multistage genetic association study was conducted of three critically ill populations phenotyped for ARDS. Stage I, a trauma cohort study (n = 224), was genotyped with a 50K gene-centric single-nucleotide polymorphism (SNP) array. We tested SNPs associated with ARDS at P < 5 × 10−4 for replication in stage II, a trauma case–control population (n = 778). SNPs replicating their association in stage II (P < 0.005) were tested in a stage III nested case–control population of mixed subjects in the intensive care unit (n = 2,063). Logistic regression was used to adjust for potential clinical confounders. We performed ELISA to test for an association between ARDS-associated genotype and plasma protein levels. Measurements and Main Results: A total of 12 SNPs met the stage I threshold for an association with ARDS. rs315952 in the IL1RN gene encoding IL-1 receptor antagonist (IL1RA) replicated its association with reduced ARDS risk in stages II (P < 0.004) and III (P < 0.02), and was robust to clinical adjustment (combined odds ratio = 0.81; P = 4.2 × 10−5). Plasma IL1RA level was associated with rs315952C in a subset of critically ill subjects. The effect of rs315952 was independent from the tandem repeat variant in IL1RN. Conclusions: The IL1RN SNP rs315952C is associated with decreased risk of ARDS in three populations with heterogeneous ARDS risk factors, and with increased plasma IL1RA response. IL1RA may attenuate ARDS risk. PMID:23449693

Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8

PubMed Central

2014-01-01

Background Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work. Methods T. crispa ethanol extract was fractionated by using different solvents. The ethanol extract and effective isolated fraction were used to investigate the potential immunomodulatory effect of different T. crispa doses ranging from 25 μg/mL to 1000 μg/mL on RAW 246.7 cells by detecting intracellular INF-γ, IL-6, and IL-8 expressions. The antioxidant activity of T. crispa was evaluated through FRAP and DPPH. The total phenolic and total flavonoid contents were also quantified. Results Results show that T. crispa extract has higher antioxidant potential than ascorbic acid. The FRAP value of T. crispa extract is 11011.11 ± 1145.42 μmol Fe+2/g, and its DPPH inhibition percentage is 55.79 ± 7.9, with 22 μg/mL IC50. The results also reveal that the total phenolic content of T. crispa extract is 213.16- ± 1.31 mg GAE/g dry stem weight, and the total flavonoid content is 62.07- ± 39.76 mg QE/g dry stem weight. T. crispa crude extract and its isolated fraction significantly stimulate RAW264.7 cell viability (P ≤ 0.05) and intracellular INF-γ, IL-6, and IL-8 expressions. The results of LC-MS show that four of the active compounds detected in the T. crispa isolated fraction are cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine. Conclusions The results of this study obviously indicate that T. crispa has immunomodulatory effects through the stimulation of INF-γ, IL-6, and IL-8 expressions. LC-MS phytochemical analysis showed that the T. crispa fraction has cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine, which may be responsible for the immunostimulator effect of T. crispa. PMID:24969238

Structural organization of the porcine and human genes coding for a leydig cell-specific insulin-like peptide (LEY I-L) and chromosomal localization of the human gene (INSL3)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burkhardt E.; Adham, I.M.; Brosig, B.

1994-03-01

Leydig insulin-like protein (LEY I-L) is a member of the insulin-like hormone superfamily. The LEY I-L gene (designated INSL3) is expressed exclusively in prenatal and postnatal Leydig cells. The authors report here the cloning and nucleotide sequence of porcine and human LEY I-L genes including the 5[prime] regions. Both genes consist of two exons and one intron. The organization of the LEY I-L gene is similar to that of insulin and relaxin. The transcription start site in the porcine and human LEY I-L gene is localized 13 and 14 bp upstream of the translation start site, respectively. Alignment of themore » 5[prime] flanking regions of both genes reveals that the first 107 nucleotides upstream of the transcription start site exhibit an overall sequence similarity of 80%. This conserved region contains a consensus TATAA box, a CAAT-like element (GAAT), and a consensus SP1 sequence (GGGCGG) at equivalent positions in both genes and therefore may play a role in regulation of expression of the LEY I-L gene. The porcine and human genome contains a single copy of the LEY I-L gene. By in situ hybridization, the human gene was assigned to bands p13.2-p12 of the short arm of chromosome 19. 25 refs., 6 figs.« less

Allium sativum L. regulates in vitro IL-17 gene expression in human peripheral blood mononuclear cells.

PubMed

Moutia, Mouna; Seghrouchni, Fouad; Abouelazz, Omar; Elouaddari, Anass; Al Jahid, Abdellah; Elhou, Abdelhalim; Nadifi, Sellama; Jamal Eddine, Jamal; Habti, Norddine; Badou, Abdallah

2016-09-29

Allium sativum L. (A.S.) "garlic", one of the most interesting medicinal plants, has been suggested to contain compounds that could be beneficial in numerous pathological situations including cancer. In this work, we aimed to assess the immunomodulatory effect of A.S. preparation on human peripheral blood mononuclear cells from healthy individuals. Nontoxic doses of A.S. were identified using MTT assay. Effects on CD4+ or CD8+ T lymphocyte proliferation were studied using flow cytometry. The effect of A.S. on cytokine gene expression was studied using qRT-PCR. Finally, qualitative analysis of A.S. was performed by HPLC approach. Data were analyzed statistically by one-way ANOVA test. The nontoxic doses of A.S. preparation did not affect neither spontaneous nor TCR-mediated CD4+ or CD8+ T lymphocyte proliferation. Interestingly, A.S. exhibited a statistically significant regulation of IL-17 gene expression, a cytokine involved in several inflammatory and autoimmune diseases. In contrast, the expression of IL-4, an anti-inflammatory cytokine, was unaffected. Qualitative analysis of A.S. ethanol preparation indicated the presence of three polyphenol bioactive compounds, which are catechin, vanillic acid and ferulic acid. The specific inhibition of the pro-inflammatory cytokine, IL-17 without affecting cell proliferation in human PBMCs by the Allium sativum L. preparation suggests a potential valuable effect of the compounds present in this plant for the treatment of inflammatory diseases and cancer, where IL-17 is highly expressed. The individual contribution of these three compounds to this global effect will be assessed.

A distinct dendritic cell population arises in the thymus of IL-13Rα1-sufficient but not IL-13Rα1-deficient mice.

PubMed

Barik, Subhasis; Miller, Mindy; Cattin-Roy, Alexis; Ukah, Tobechukwu; Zaghouani, Habib

2018-06-18

IL-13 receptor alpha 1 (IL-13Rα1) associates with IL-4Rα to form a functional IL-4Rα/IL-13Rα1 heteroreceptor (HR) through which both IL-4 and IL-13 signal. Recently, HR expression was associated with the development of M2 type macrophages which function as antigen presenting cells (APCs). Herein, we show that a subset of thymic resident dendritic cells (DCs) expressing high CD11b (CD11b hi ) and intermediate CD11c (CD11c int ) arise in HR-sufficient but not HR-deficient mice. These DCs, which originate from the bone marrow are able to take up Ag from the peritoneum, traffic through the spleen and the lymph nodes and carry it to the thymus. In addition, since the DCs are able to present Ag to T cells, express high levels of the costimulatory molecule CD24, and comprise a CD8α + subset, it is likely that the cells contribute to T cell development and perhaps negative selection of self-reactive lymphocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo.

PubMed

Connor, Lisa M; Tang, Shiau-Choot; Camberis, Mali; Le Gros, Graham; Ronchese, Franca

2014-09-15

Dendritic cells (DC) are critical for the initiation of immune responses; however, their role in priming IL-4-producing Th2 cells in vivo is not fully understood. We used a model of intradermal injection with fluorescent-labeled, nonviable larvae from the helminth parasite nonviable Nippostrongylus brasiliensis L3 larvae (Nb), a strong inducer of Th2 responses, together with IL-4-GFP reporter mice that enable a sensitive detection of IL-4 production to examine the contribution of DC to the priming of IL-4-producing CD4(+) T cells in vivo. We found that parasite material is taken up by two distinct DC populations in draining lymph nodes: a mostly CD11c(int)MHC class II (MHCII)(hi)CD11b(+)Ly6C(-) dermal DC population and a CD11c(hi)MHCII(int)CD11b(+)Ly6C(+) monocyte-derived DC population. After Nb treatment, these two DC populations appeared in the draining lymph nodes in comparable numbers and with similar kinetics; however, treatment with pertussis toxin blocked the migration of dermal DC and the priming of IL-4-producing T cells, but only partially affected monocyte-derived DC numbers. In line with this observation, transfer of OVA-loaded CD11c(int)MHCII(hi) DC from Nb-treated mice into naive hosts could sensitize OVA-specific CD4(+) T cells to IL-4 production, whereas transfer of CD11c(int)MHCII(hi) DC from naive mice, or CD11c(hi)MHCII(int) DC from Nb-treated or naive mice, induced CD4(+) T cell expansion but no IL-4 production. Phenotypic analysis of Nb-loaded CD11c(int)MHCII(hi) DC revealed expression of programmed death ligand 2, CD301b, IFN regulatory factor 4, and moderate upregulation of OX40 ligand. However, thymic stromal lymphopoietin and OX40 ligand were not required for Th2 priming. Thus, our data suggest that appropriate stimuli can induce DC to express the unique signals sufficient to direct CD4(+) T cells to Th2 differentiation. Copyright © 2014 by The American Association of Immunologists, Inc.

IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging.

PubMed

Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro

2015-07-10

Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

PubMed Central

Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P

2015-01-01

ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs.

PubMed

Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P; Esteves, Pedro J

2015-11-01

ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. © The Author(s) 2015.

IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis

PubMed Central

Chahbi, Mayssa; Haouami, Youssra; Sfar, Imen; Abdelmoula, Leila; Ben Abdallah, Taieb; Gorgi, Yousr

2018-01-01

Background Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity. Methods In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin. Results There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849–0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels’ analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6. Conclusion IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence. PMID:29584788

Kynurenic acid downregulates IL-17/1L-23 axis in vitro.

PubMed

Salimi Elizei, Sanam; Poormasjedi-Meibod, Malihe-Sadat; Wang, Xia; Kheirandish, Maryam; Ghahary, Aziz

2017-07-01

Exploring the function of interleukin (IL) 17 and related cytokine interactions have been proven useful toward understanding the role of inflammation in autoimmune diseases. Production of the inflammatory cytokine IL-23 by dendritic cells (DC's) has been shown to promote IL-17 expression by Th17 cells. It is well established that Th17 cells play an important role in several autoimmune diseases including psoriasis and alopecia. Our recent investigations have suggested that Kynurenine-rich environment can shift a pro-inflammatory response to an anti-inflammatory response, as is the case in the presence of the enzyme Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation and Kynurenine (Kyn) production. In this study, we sought to explore the potential role of kynurenic acid (KynA), in modulating the expression of IL-23 and IL-17 by DCs and CD4 + cells, respectively. The result of flow cytometry demonstrated that the frequency of IL-23-producing DCs is reduced with 100 µg/ml of KynA as compared with that of LPS-stimulated DCs. KynA (100 μg/ml) addition to activated T cells significantly decreased the level of IL-17 mRNA and frequency of IL-17 + T cells as compared to that of concanavalin (Con) A-activated T cells. To examine the mechanism of the suppressive role of KynA on IL-23/IL-17 in these cells, cells were treated with 3 μM G-protein-coupled receptor35 (GPCR35) inhibitor (CID), for 60 min. The result showed that the reduction of both adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) by KynA is involved in suppression of LPS-induced IL-23p19 expression. Since GPCR35 is also detected on T cells; therefore, it is concluded that KynA plays an important role in modulating the expression of IL-23 and IL-17 in DCs and Th17 cells through inhibiting GPCR35 and downregulation of both AC and cAMP.

Extensive peptide and natural protein substrate screens reveal that mouse caspase-11 has much narrower substrate specificity than caspase-1

PubMed Central

Ramirez, Monica L. Gonzalez; Poreba, Marcin; Snipas, Scott J.; Groborz, Katarzyna; Drag, Marcin; Salvesen, Guy S.

2018-01-01

Inflammatory cell death, or pyroptosis, is triggered by pathogenic infections or events. It is executed by caspase-1 (in the canonical pyroptosis pathway) or caspase-11 (noncanonical pathway), each via production of a cell-lytic domain from the pyroptosis effector protein gasdermin D through specific and limited proteolysis. Pyroptosis is accompanied by the release of inflammatory mediators, including the proteolytically processed forms of interleukin-1β (IL-1β) and IL-18. Given the similar inflammatory outcomes of the canonical and noncanonical pyroptosis pathways, we hypothesized that caspase-1 and -11 should have very similar activities and substrate specificities. To test this hypothesis, we purified recombinant murine caspases and analyzed their primary specificities by massive hybrid combinatorial substrate library (HyCoSuL) screens. We correlated the substrate preferences of each caspase with their activities on the recombinant natural substrates IL-1β, IL-18, and gasdermin D. Although we identified highly selective and robust peptidyl substrates for caspase-1, we were unable to do so for caspase-11, because caspase-1 cleaved even the best caspase-11 substrates equally well. Caspase-1 rapidly processed pro-IL-1β and -18, but caspase-11 processed these two pro-ILs extremely poorly. However, both caspase-1 and -11 efficiently produced the cell-lytic domain from the gasdermin D precursor. We hypothesize that caspase-11 may have evolved a specific exosite to selectively engage pyroptosis without directly activating pro-IL-1β or -18. In summary, comparing the activities of caspase-1 and -11 in HyCoSuL screens and with three endogenous protein substrates, we conclude that caspase-11 has highly restricted substrate specificity, preferring gasdermin D over all other substrates examined. PMID:29414788

Extensive peptide and natural protein substrate screens reveal that mouse caspase-11 has much narrower substrate specificity than caspase-1.

PubMed

Ramirez, Monica L Gonzalez; Poreba, Marcin; Snipas, Scott J; Groborz, Katarzyna; Drag, Marcin; Salvesen, Guy S

2018-05-04

Inflammatory cell death, or pyroptosis, is triggered by pathogenic infections or events. It is executed by caspase-1 (in the canonical pyroptosis pathway) or caspase-11 (noncanonical pathway), each via production of a cell-lytic domain from the pyroptosis effector protein gasdermin D through specific and limited proteolysis. Pyroptosis is accompanied by the release of inflammatory mediators, including the proteolytically processed forms of interleukin-1β (IL-1β) and IL-18. Given the similar inflammatory outcomes of the canonical and noncanonical pyroptosis pathways, we hypothesized that caspase-1 and -11 should have very similar activities and substrate specificities. To test this hypothesis, we purified recombinant murine caspases and analyzed their primary specificities by massive hybrid combinatorial substrate library (HyCoSuL) screens. We correlated the substrate preferences of each caspase with their activities on the recombinant natural substrates IL-1β, IL-18, and gasdermin D. Although we identified highly selective and robust peptidyl substrates for caspase-1, we were unable to do so for caspase-11, because caspase-1 cleaved even the best caspase-11 substrates equally well. Caspase-1 rapidly processed pro-IL-1β and -18, but caspase-11 processed these two pro-ILs extremely poorly. However, both caspase-1 and -11 efficiently produced the cell-lytic domain from the gasdermin D precursor. We hypothesize that caspase-11 may have evolved a specific exosite to selectively engage pyroptosis without directly activating pro-IL-1β or -18. In summary, comparing the activities of caspase-1 and -11 in HyCoSuL screens and with three endogenous protein substrates, we conclude that caspase-11 has highly restricted substrate specificity, preferring gasdermin D over all other substrates examined. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Ultra Low Loss Optical Fiber Cable Assemblies. Volume 2.

DTIC Science & Technology

1983-06-07

Bell Jar Vacuum Chamber 3.2.4 Contact Epoxying Fixture with Heat Controller (Hughes #I143690S or equivalent ) 3.2.5 VA 211,606-2, 10 cc Disposable...2.2 1,L2111111. ’A 0 I2 11ll11.25 111111.4 111.6 MICROCOPY RESOLUTION TEST CHART NA?,ONAL BUREAU OF STANDaOS-I96S-A I RESEARCH AND DEVELOPMENT...and uncouple, be coated with a non -reflective finish which is environment resistant, and sealed so that it will not allow water to enter the connector

Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

PubMed Central

Bravenboer, Nathalie

2016-01-01

During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs). hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL) for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold), as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair. PMID:27667999

Role of cytokines (TNF-alpha, IL-1beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide.

PubMed

Melo, Maria Luisa P; Brito, Gerly A C; Soares, Rudy C; Carvalho, Sarah B L M; Silva, Johan V; Soares, Pedro M G; Vale, Mariana L; Souza, Marcellus H L P; Cunha, Fernando Q; Ribeiro, Ronaldo A

2008-04-01

Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11. Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and KC ELISA. CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea. These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

U.S. EPA, Pesticide Product Label, CARBARYL 50-W INSECTICIDE, 11/16/1972

EPA Pesticide Factsheets

2011-04-21

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Military Services Fitness Database: Development of a Computerized Physical Fitness and Weight Management Database for the U.S. Army

DTIC Science & Technology

2009-01-01

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Diagnostic value of T-Spot TB combined with INF-γ and IL-27 in tuberculous pleurisy

PubMed Central

Zhang, Meng; Xiong, Dedong; Li, Hongxia; Wang, Zonglan; Li, Renzhe

2018-01-01

The purpose of the present study was to investigate the diagnostic value of T cells spot test (T-Spot TB) combined with interferon-γ (INF-γ) and interleukin-27 (IL-27) in tuberculous pleurisy. Sixty patients with tuberculous pleurisy (observation group) and 60 patients with non-tuberculous pleurisy (control group) were enrolled in this study. T-Spot TB was performed to detect the pleural effusion of two groups of patients. Levels of IFN-γ and IL-27 in serum and pleural effusion were detected by enzyme-linked immunosorbent assay (ELISA). Relative expression of IFN-γ mRNA and IL-27 mRNA in peripheral blood mononuclear cells were detected by RT-PCR. Positive rate of T-Spot TB in observation group was 96.7% (58 cases), which was significantly higher than that in control group (p<0.05). Concentration of INF-γ in pleural effusion of observation group was 468.6±24.8 ng/l, which was significantly higher than that in control group (131.3±18.7 ng/l, p<0.05). Concentration of IL-27 in pleural effusion of observation group was 423.4±37.2 ng/l, which was significantly higher than that in control group (116.2±15.5 ng/l, p<0.05). Concentrations of INF-γ and IL-27 in serum of observation group were 48.2±13.4 and 41.7±10.6 ng/l, respectively, which were significantly higher than those in control group (38.6±11.2 and 35.3±8.4 ng/l, p<0.05). Relative expression levels of INF-γ mRNA and IL-27 mRNA in observation group were significantly higher than those in control group (p<0.05). Therefore, combination of T-Spot TB with INF-γ and IL-27 has significant application value in the clinical diagnosis of tuberculous pleurisy, and should be popularized. PMID:29399137

Diagnostic value of T-Spot TB combined with INF-γ and IL-27 in tuberculous pleurisy.

PubMed

Zhang, Meng; Xiong, Dedong; Li, Hongxia; Wang, Zonglan; Li, Renzhe

2018-02-01

The purpose of the present study was to investigate the diagnostic value of T cells spot test (T-Spot TB) combined with interferon-γ (INF-γ) and interleukin-27 (IL-27) in tuberculous pleurisy. Sixty patients with tuberculous pleurisy (observation group) and 60 patients with non-tuberculous pleurisy (control group) were enrolled in this study. T-Spot TB was performed to detect the pleural effusion of two groups of patients. Levels of IFN-γ and IL-27 in serum and pleural effusion were detected by enzyme-linked immunosorbent assay (ELISA). Relative expression of IFN-γ mRNA and IL-27 mRNA in peripheral blood mononuclear cells were detected by RT-PCR. Positive rate of T-Spot TB in observation group was 96.7% (58 cases), which was significantly higher than that in control group (p<0.05). Concentration of INF-γ in pleural effusion of observation group was 468.6±24.8 ng/l, which was significantly higher than that in control group (131.3±18.7 ng/l, p<0.05). Concentration of IL-27 in pleural effusion of observation group was 423.4±37.2 ng/l, which was significantly higher than that in control group (116.2±15.5 ng/l, p<0.05). Concentrations of INF-γ and IL-27 in serum of observation group were 48.2±13.4 and 41.7±10.6 ng/l, respectively, which were significantly higher than those in control group (38.6±11.2 and 35.3±8.4 ng/l, p<0.05). Relative expression levels of INF-γ mRNA and IL-27 mRNA in observation group were significantly higher than those in control group (p<0.05). Therefore, combination of T-Spot TB with INF-γ and IL-27 has significant application value in the clinical diagnosis of tuberculous pleurisy, and should be popularized.

Effect of mitomycin C on IL-1R expression, IL-1-related hepatocyte growth factor secretion and corneal epithelial cell migration.

PubMed

Chen, Tsan-Chi; Chang, Shu-Wen

2010-03-01

To investigate how mitomycin C (MMC) modulates hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) secretions in human corneal fibroblasts and regulates human corneal epithelial (HCE) cell migration. Primary human corneal fibroblasts were treated with MMC (0.05, 0.1, or 0.2 mg/mL for 5 minutes) and were cultivated with or without interleukin (IL)-1beta. Transcript and secretion of HGF and KGF were determined by quantitative real-time RT-PCR and Western blot analysis, respectively. The effect of MMC-treated fibroblasts on HCE cell migration was evaluated using a transwell migration assay. The influence of MMC on HGF expression/secretion and HCE cell migration was further confirmed by RNA interference. The number of IL-1 receptors (IL-1R) on the fibroblast surface was analyzed by flow cytometry. MMC alone did not affect endogenous HGF expression, whereas IL-1beta alone significantly upregulated HGF transcripts and secretion. By modifying IL-1R numbers, MMC further upregulated IL-1beta-related HGF expression at a concentration of 0.05 mg/mL but to a lesser extent at 0.1 and 0.2 mg/mL. KGF transcripts and intracellular expression were suppressed by MMC dose dependently in the presence or absence of IL-1beta, whereas KGF secretion was not affected. Conditioned medium from MMC-treated fibroblasts exerted a similar concentration-dependent effect on HCE cell migration, enhancing migration most significantly at 0.05 mg/mL MMC in the presence of IL-1beta. The MMC dose-dependent modulation of HCE cell migration was abolished in HGF-silenced fibroblasts. MMC differentially modulated IL-1R expression at various concentrations and regulated HGF and KGF differently. MMC alone did not alter HGF expression. In the presence of IL-1beta, MMC-treated corneal fibroblasts modified HCE cell migration through IL-1beta-induced HGF secretion.

Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.

PubMed

Jemaa, Awatef Ben; Bouraoui, Yosra; Rais, Nawfel Ben; Nouira, Yassine; Oueslati, Ridha

2016-12-01

Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones. Copyright © 2016 Elsevier GmbH. All rights reserved.

Development of an interleukin (IL)-33 sandwich ELISA kit specific for mature IL-33.

PubMed

Kim, Eunsom; Kwak, Areum; Jhun, Hyunjhung; Lee, Siyoung; Jo, Seunghyun; Lee, Jongho; Kang, Tae-Bong; Her, Erk; Bae, Suyoung; Lee, Youngmin; Kim, Soohyun

2016-01-01

Interleukin (IL)-33 is an inflammatory cytokine and belongs to the IL-1 family of cytokines. There are eleven members of the IL-1 family of cytokines and all have important roles in host defense against infections. Their levels are increased during infection and in various auto-inflammatory diseases. IL-33 is also associated with autoimmune diseases such as asthma, atopic dermatitis, rheumatoid arthritis, and atherosclerosis. IL-33 receptors consist of IL-1R4 and IL-1R3 to induce both Th1 and Th2 type immune response. Here we present the development of monoclonal antibodies (mAbs) against human mature IL-33. Recombinant human mature IL-33 protein was expressed in E. coli and purified by multi-step affinity chromatography. The human IL-33 activity was examined in HMC-1 and Raw 264.7 cells. Mice were immunized with the biologically active mature IL-33 to generate mAb against IL-33. The anti-IL-33 mAb (clone/4) was used as a capture antibody for a sandwich enzyme-linked immunosorbent assay (ELISA). This assay detects mature IL-33 with a high sensitivity (80 pg/mL) but does not recognize the biologically inactive precursor IL-33. This article describes the methods for a newly developed IL-33 ELISA kit that is specific for mature IL-33 and may be used to analyze bioactive mature IL-33 in various immunological diseases.

L-arginine transport in retinas from streptozotocin diabetic rats: correlation with the level of IL-1 beta and NO synthase activity.

PubMed

Carmo, A; Cunha-Vaz, J G; Carvalho, A P; Lopes, M C

1999-11-01

Several evidences suggest that the pro-inflammatory cytokines IL-1 beta and the radical NO are implicated as effectors molecules in the pancreatic beta-cells dysfunction; an event preceding the pathogenesis of diabetes. IL-1 beta induces the expression of the inducible isoform of NO synthase (iNOS), which use L-arginine as substrate to overproduce NO. However, it is not known whether these events may participate in the development of diabetic retinopathy, which is the main cause of blindness. In this work, we found an increased level of IL-1 beta in retinas from streptozotocin-induced (STZ) diabetic rats. We also observed that the activity of the NO synthase (NOS) and the L-arginine uptake are enhanced in retinas from STZ-induced diabetic rats as compared to retinas from control rats. We found that the uptake of L-arginine in retinas from control and diabetic rats occurs through a transporter resembling the Y + system, i.e. it is saturable, not affected over the pH range 6.5 to 7.4, and is independent of the extracellular Na+. Nevertheless, the L-arginine transport in retinas from diabetic rats occurs through a carrier with lower affinity (K(m) = 25 microM) and higher capacity (Vmax = 295 +/- 22.4 pmol L-arginine/mg protein) than in retinas from control rats (K(m) = 5 microM and Vmax = 158 +/- 12.8 pmol L-arginine/mg protein) which is correlated with the increased NOS activity and consequent depletion of the intracellular pool of L-arginine.

Effect of calcitriol on in vitro whole blood cytokine production in critically ill dogs.

PubMed

Jaffey, J A; Amorim, J; DeClue, A E

2018-06-01

Hypovitaminosis D has been identified as a predictor of mortality in human beings, dogs, cats and foals. However, the immunomodulatory effects of vitamin D in critically ill dogs has not been evaluated. The aim of this study was to evaluate the effect of calcitriol on cytokine production from whole blood collected from critically ill dogs in vitro. Twelve critically ill dogs admitted to a veterinary intensive care unit (ICU) were enrolled in a prospective cohort study. Whole blood from these dogs was incubated with calcitriol (2×10 -7 M) or ethanol (control) for 24h. Subsequent to this incubation, lipopolysaccharide (LPS)-stimulated whole blood production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were measured using a canine-specific multiplex assay. Calcitriol significantly increased LPS-stimulated whole blood production of IL-10 and decreased TNF-α production without significantly altering IL-6 production. There was no significant difference in whole blood cytokine production capacity between survivors and non-survivors at the time of discharge from the ICU or 30days after discharge. These data suggests that calcitriol induces an anti-inflammatory phenotype in vitro in whole blood from critically ill dogs. Copyright © 2018 Elsevier Ltd. All rights reserved.

C-reactive protein in critically ill cancer patients with sepsis: influence of neutropenia

PubMed Central

2011-01-01

Introduction Several biomarkers have been studied in febrile neutropenia. Our aim was to assess C-reactive protein (CRP) concentration in septic critically ill cancer patients and to compare those with and without neutropenia. Methods A secondary analysis of a matched case-control study conducted at an oncologic medical-surgical intensive care unit (ICU) was performed, segregating patients with severe sepsis/septic shock. The impact of neutropenia on CRP concentrations at admission and during the first week of ICU stay was assessed. Results A total of 154 critically ill septic cancer patients, 86 with neutropenia and 68 without, were included in the present study. At ICU admission, the CRP concentration of neutropenic patients was significantly higher than in non-neutropenic patients, 25.9 ± 11.2 mg/dL vs. 19.7 ± 11.4 mg/dL (P = 0.009). Among neutropenic patients, CRP concentrations at ICU admission were not influenced by the severity of neutropenia (< 100/mm3 vs. ≥ 100/mm3 neutrophils), 25.1 ± 11.6 mg/dL vs. 26.9 ± 10.9 mg/dL (P = 0.527). Time dependent analysis of CRP from Day 1 to Day 7 of antibiotic therapy showed an almost parallel decrease in both groups (P = 0.335), though CRP of neutropenic patients was, on average, always higher in comparison to that of non-neutropenic patients. Conclusions In septic critically ill cancer patients CRP concentrations are more elevated in those with neutropenia. However, the CRP course seems to be independent from the presence or absence of neutropenia. PMID:21595932

Parasite-specific IL-17-type cytokine responses and soluble IL-17 receptor levels in Alveolar Echinococcosis patients.

PubMed

Lechner, Christian J; Grüner, Beate; Huang, Xiangsheng; Hoffmann, Wolfgang H; Kern, Peter; Soboslay, Peter T

2012-01-01

Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis, is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA) and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host.

[Changes of CD(4)(+)Foxp3(+) regulatory T cells and CD(4)(+)IL-17(+)T cells in cigarette smoke-exposed rats].

PubMed

Meng, Jing-jing; Zhong, Xiao-ning; Bai, Jing; He, Zhi-yi; Zhang, Jian-quan; Huang, Qiu-pin

2012-01-01

To evaluate the changes of CD(4)(+)IL-17(+) T (Th17) and CD(4)(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF), and therefore to explore the role of Th17 and Treg in cigarette smoke-induced airway inflammation/COPD in rats. Forty male Wistar rats were randomly divided into 4 groups: a 12 wk smoke-exposure group, a 24 wk smoke-exposure group, a 12 wk control group and a 24 wk control group (n = 10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts. IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17(+) T and CD(4)(+)Foxp3(+) Treg in peripheral blood and BALF were determined by flow cytometry. The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. Levels of IL-17 were remarkable increased in the 12 wk smoke-exposure group and the 24 wk smoke-exposure group in serum [(52.6 ± 1.8) ng/L, (75.4 ± 6.0) ng/L] and BALF [(78.1 ± 5.8) ng/L, (95.0 ± 6.8) ng/L] compared with the 12 wk control group [(40.0 ± 3.2)ng/L, (54.5 ± 4.6) ng/L] and the 24 wk control group [(36.7 ± 3.2) ng/L, (53.9 ± 3.7) ng/L], all P < 0.05. IL-6 in serum was significantly increased in the 24 wk smoke-exposure group [(31.4 ± 2.1) ng/L] compared with the 24 wk control group [(11.5 ± 0.5) ng/L], and it was increased in the 12 wk and the 24 wk smoke-exposure group [(33.3 ± 2.3) ng/L, (44.6 ± 3.0) ng/L] compared with the 12 wk and the 24 wk control group [(15.6 ± 1.8) ng/L, (18.0 ± 1.9) ng/L] in BALF. Ratio of Th17 was higher in the 12 wk and the 24 wk smoke-exposure groups in peripheral blood [(1.81 ± 0.19)%, (3.74 ± 0.55)%] and BALF [(7.84 ± 0.28)%, (8.01 ± 0.39)%] compared with the12 wk [(0.97 ± 0.08)%, (5.64 ± 0.54)%] and the 24 wk control group [(1

U.S. EPA, Pesticide Product Label, , 11/03/1981

EPA Pesticide Factsheets

2011-04-21

... '" ;Iq, t ..... JILt''':' Ul',t! I;~ ,h, " •• ( W' ·,.1··.·\\ I;"'1i ". ,1"'.'' II), It· HIQt'1I, • 1t·,1·'~.f·'1 t.·" "I' ',',1 ,,~ ".JIlt··" ,;11'1, 'I .. : (, Il~,,, ' of' l' .., . ...

The Role of IL-17 in the Angiogenesis of Rheumatoid Arthritis

DTIC Science & Technology

2011-07-01

IL-17RC IL-17+ anti-IL-17RA anti-IL-17RC CB EDA F 10 20 30 40 50 60 m ea n n u m b er o f tu b es /w el l PBS bFGF * IgG * anti-IL-17RA anti-IL-17RC...s/ w el l PBS * 50 ng/ml IL-17 DMSO 1 5 M SPM PD * * bFGF 51 51 M LY G Page 9 IL-17 (50ng/ml) plus DMSO (C), IL-17 (50ng/ml) plus LY294002 (5...injection for histological studies. Levels of IL-17 were quantified by ELISA on days 4 and 10 from ankles treated with Ad-IL-17 or Ad-CMV control. Abs and

Interleukin-23 (IL-23), independent of IL-17 and IL-22, drives neutrophil recruitment and innate inflammation during Clostridium difficile colitis in mice.

PubMed

McDermott, Andrew J; Falkowski, Nicole R; McDonald, Roderick A; Pandit, Chinmay R; Young, Vincent B; Huffnagle, Gary B

2016-01-01

Our objective was to determine the role of the inflammatory cytokine interleukin-23 (IL-23) in promoting neutrophil recruitment, inflammatory cytokine expression and intestinal histopathology in response to Clostridium difficile infection. Wild-type (WT) and p19(-/-) (IL-23KO) mice were pre-treated with cefoperazone in their drinking water for 5 days, and after a 2-day recovery period were challenged with spores from C. difficile strain VPI 10463. Interleukin-23 deficiency was associated with significant defects in both the recruitment of CD11b(High) Ly6G(H) (igh) neutrophils to the colon and the expression of neutrophil chemoattractants and stabilization factors including Cxcl1, Cxcl2, Ccl3 and Csf3 within the colonic mucosa as compared with WT animals. Furthermore, the expression of inflammatory cytokines including Il33, Tnf and Il6 was significantly reduced in IL-23-deficient animals. There was also a trend towards less severe colonic histopathology in the absence of IL-23. The induction of Il17a and Il22 was also significantly abrogated in IL-23KO mice. Inflammatory cytokine expression and neutrophilic inflammation were not reduced in IL-17a-deficient mice or in mice treated with anti-IL-22 depleting monoclonal antibody. However, induction of RegIIIg was significantly reduced in animals treated with anti-IL-22 antibody. Taken together, these data indicate that IL-23, but not IL-17a or IL-22, promotes neutrophil recruitment and inflammatory cytokine and chemokine expression in the colon in response to C. difficile infection. © 2015 John Wiley & Sons Ltd.

Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Santiago-Hernández, Jean J; Pérez-Hernández, Nonanzit; Ramírez-Fuentes, Silvestre; Fragoso, José Manuel; Vargas-Alarcón, Gilberto

2011-07-01

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities. To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

Aneurysmal subarachnoid hemorrhage lead to systemic upregulation of IL-23/IL-17 inflammatory axis.

PubMed

Chaudhry, Shafqat Rasul; Güresir, Erdem; Vatter, Hartmut; Kinfe, Thomas M; Dietrich, Dirk; Lamprecht, Alf; Muhammad, Sajjad

2017-09-01

IL-23 and IL-17 are pro-inflammatory cytokines. IL-23 is secreted by activated macrophages and dendritic cells, while IL-17 by Th17 cells. Serum IL-23 and IL-17 are known to be elevated in numerous inflammatory diseases including neurodegenerative diseases. The role of serum IL-23 and IL-17 in aneurysmal subarachnoid hemorrhage (aSAH) has still not been investigated. The present work investigates the serum IL-23 and IL-17 levels and their association with post hemorrhagic complications and clinical outcome in patients with aSAH. In this study, 80 patients with aSAH (Hunt and Hess grade I-V) were prospectively recruited. We enrolled 24 control patients with lumbar spinal stenosis. Peripheral venous blood was withdrawn from controls and from aSAH patients at day 1 and day 7, allowed to clot and centrifuged to obtain serum. Enzyme linked immunoassay kits were employed to quantify the serum levels of IL-23 and IL-17 by applying 50µL of serum samples. Post hemorrhagic complications and clinical outcome were documented prospectively from patient's hospital record. Serum IL-23 and IL-17 levels were significantly elevated in aSAH patients at day 1 and day 7 (n=80) as compared to control patients (n=24). Further analysis after dichotomy of patients who suffered from post hemorrhagic complications including cerebral vasospasm, chronic hydrocephalus, seizures, cerebral ischemia, delayed neurological deficits showed differential correlations with different post hemorrhagic complications (Table 1). Serum IL-23 and IL-17 levels did not correlate with clinical outcome. Serum IL-23 and IL-17 levels were elevated in patients with aSAH showing upregulation of IL-23/IL-17 inflammatory axis after aSAH. Serum IL-23 and IL-17 showed differential correlations with post hemorrhagic complications and no correlation with clinical outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

T cell source of type 1 cytokines determines illness patterns in respiratory syncytial virus-infected mice.

PubMed Central

Tang, Y. W.; Graham, B. S.

1997-01-01

Manipulation of the cytokine microenvironment at the time of vaccination can influence immune responses to remote challenge, providing a strategy to study the molecular pathogenesis of respiratory syncytial virus (RSV) vaccine-enhanced disease in the mouse model. Although treatment with antibody against IL-4 or recombinant IL-12 (rIL-12) at the time of formalin-inactivated RSV vaccination induced a similar shift in the pattern of cytokine mRNA expression upon live virus challenge, anti-IL-4 treated mice had increased CD8+ cytotoxic T lymphocyte activity and reduced illness compared with rIL-12-treated mice. To define effector mechanisms responsible for these patterns, CD4+ and/or CD8+ T lymphocytes were selectively depleted in vivo at the time of RSV challenge. In rIL-12-treated mice, CD4+ lymphocytes made the largest contribution to IFN-gamma mRNA, RSV clearance, and illness, while in anti-IL-4 treated mice, CD8+ lymphocytes were the major effector. The effector responsible for virus clearance also mediated illness, suggesting that efficiency of virus clearance determined disease expression. These results demonstrate that the phenotype of effector cells involved in the immune response to virus challenge may be a more important determinant of disease than patterns of cytokine expression classically assigned to Th1 and Th2 lymphocytes. PMID:9151790

Arsenate exposure affects amino acids, mineral nutrient status and antioxidants in rice (Oryza sativa L.) genotypes.

PubMed

Dwivedi, S; Tripathi, R D; Tripathi, P; Kumar, A; Dave, R; Mishra, S; Singh, R; Sharma, D; Rai, U N; Chakrabarty, D; Trivedi, P K; Adhikari, B; Bag, M K; Dhankher, O P; Tuli, R

2010-12-15

Simulated pot experiments were conducted on four rice (Oryza sativa L.) genotypes (Triguna, IR-36, PNR-519, and IET-4786) to examine the effects of As(V) on amino acids and mineral nutrient status in grain along with antioxidant response to arsenic exposure. Rice genotypes responded differentially to As(V) exposure in terms of amino acids and antioxidant profiles. Total amino acid content in grains of all rice genotypes was positively correlated with arsenic accumulation. While, most of the essential amino acids increased in all cultivars except IR-36, glutamic acid and glycine increased in IET-4786 and PNR-519. The level of nonprotein thiols (NPTs) and the activities of superoxide dismutase (SOD; EC 1.15.1.1), glutathione reductase (GR; EC 1.6.4.2) and ascorbate peroxidase (APX; EC 1.11.1.11) increased in all rice cultivars except IET-4786. A significant genotypic variation was also observed in specific arsenic uptake (SAU; mg kg(-1)dw), which was in the order of Triguna (134) > IR-36 (71) > PNR-519 (53) > IET-4786 (29). Further, application of As(V) at lower doses (4 and 8 mg L(-1) As) enhanced the accumulation of selenium (Se) and other nutrients (Fe, P, Zn, and S), however, higher dose (12 mg L(-1) As) limits the nutrient uptake in rice. In conclusion, low As accumulating genotype, IET-4786, which also had significantly induced level of essential amino acids, seems suitable for cultivation in moderately As contaminated soil and would be safe for human consumption.

Identification of IL6R and chromosome 11q13.5 as risk loci for asthma.

PubMed

Ferreira, Manuel A R; Matheson, Melanie C; Duffy, David L; Marks, Guy B; Hui, Jennie; Le Souëf, Peter; Danoy, Patrick; Baltic, Svetlana; Nyholt, Dale R; Jenkins, Mark; Hayden, Catherine; Willemsen, Gonneke; Ang, Wei; Kuokkanen, Mikko; Beilby, John; Cheah, Faang; de Geus, Eco J C; Ramasamy, Adaikalavan; Vedantam, Sailaja; Salomaa, Veikko; Madden, Pamela A; Heath, Andrew C; Hopper, John L; Visscher, Peter M; Musk, Bill; Leeder, Stephen R; Jarvelin, Marjo-Riitta; Pennell, Craig; Boomsma, Dorret I; Hirschhorn, Joel N; Walters, Haydn; Martin, Nicholas G; James, Alan; Jones, Graham; Abramson, Michael J; Robertson, Colin F; Dharmage, Shyamali C; Brown, Matthew A; Montgomery, Grant W; Thompson, Philip J

2011-09-10

We aimed to identify novel genetic variants affecting asthma risk, since these might provide novel insights into molecular mechanisms underlying the disease. We did a genome-wide association study (GWAS) in 2669 physician-diagnosed asthmatics and 4528 controls from Australia. Seven loci were prioritised for replication after combining our results with those from the GABRIEL consortium (n=26,475), and these were tested in an additional 25,358 independent samples from four in-silico cohorts. Quantitative multi-marker scores of genetic load were constructed on the basis of results from the GABRIEL study and tested for association with asthma in our Australian GWAS dataset. Two loci were confirmed to associate with asthma risk in the replication cohorts and reached genome-wide significance in the combined analysis of all available studies (n=57,800): rs4129267 (OR 1·09, combined p=2·4×10(-8)) in the interleukin-6 receptor (IL6R) gene and rs7130588 (OR 1·09, p=1·8×10(-8)) on chromosome 11q13.5 near the leucine-rich repeat containing 32 gene (LRRC32, also known as GARP). The 11q13.5 locus was significantly associated with atopic status among asthmatics (OR 1·33, p=7×10(-4)), suggesting that it is a risk factor for allergic but not non-allergic asthma. Multi-marker association results are consistent with a highly polygenic contribution to asthma risk, including loci with weak effects that might be shared with other immune-related diseases, such as NDFIP1, HLA-B, LPP, and BACH2. The IL6R association further supports the hypothesis that cytokine signalling dysregulation affects asthma risk, and raises the possibility that an IL6R antagonist (tocilizumab) may be effective to treat the disease, perhaps in a genotype-dependent manner. Results for the 11q13.5 locus suggest that it directly increases the risk of allergic sensitisation which, in turn, increases the risk of subsequent development of asthma. Larger or more functionally focused studies are needed to

Identification of IL6R and chromosome 11q13.5 as risk loci for asthma

PubMed Central

Ferreira, Manuel A.R.; Matheson, Melanie C.; Duffy, David L.; Marks, Guy B.; Hui, Jennie; Le Souëf, Peter; Danoy, Patrick; Baltic, Svetlana; Nyholt, Dale R.; Jenkins, Mark; Hayden, Catherine; Willemsen, Gonneke; Ang, Wei; Kuokkanen, Mikko; Beilby, John; Cheah, Faang; de Geus, Eco J. C.; Ramasamy, Adaikalavan; Vedantam, Sailaja; Salomaa, Veikko; Madden, Pamela A.; Heath, Andrew C.; Hopper, John L.; Visscher, Peter M.; Musk, Bill; Leeder, Stephen R.; Jarvelin, Marjo-Riitta; Pennell, Craig; Boomsma, Dorret I.; Hirschhorn, Joel; Walters, Haydn; Martin, Nicholas G.; James, Alan; Jones, Graham; Abramson, Michael J.; Robertson, Colin F.; Dharmage, Shyamali C.; Brown, Matthew A.; Montgomery, Grant W.; Thompson, Philip J.

2012-01-01

Background We aimed to identify novel genetic variants affecting asthma risk, since these might provide novel insights into molecular mechanisms underlying asthma. Methods We performed a genome-wide association study (GWAS) in 2,669 physician-diagnosed asthmatics and 4,528 controls from Australia. Seven loci were prioritised for replication after combining our results with those from the GABRIEL consortium (n=26,475), and these were tested in an additional 25,358 independent samples from four in-silico cohorts. Quantitative multi-SNP scores of genetic load were constructed on the basis of results from the GABRIEL study and tested for association with asthma in our Australian GWAS dataset. Findings Two loci were confirmed to associate with asthma risk in the replication cohorts and reached genome-wide significance in the combined analysis of all available studies (n=57,800): rs4129267 (OR=1.09, combined P=2.4×10−8) in the interleukin-6 receptor gene (IL6R) and rs7130588 (OR=1.09, P=1.8×10−8) on chromosome 11q13.5 near the leucine-rich repeat containing 32 gene (LRRC32, also known as GARP). The 11q13.5 locus was significantly associated with atopic status among asthmatics (OR = 1.33, P = 7×10−4), suggesting that it is a risk factor for allergic but not non-allergic asthma. Multi-SNP association results are consistent with a highly polygenic contribution to asthma risk, including loci with weak effects that may be shared with other immune-related diseases, such as NDFIP1, HLA-B, LPP and BACH2. Interpretation The IL6R association further supports the hypothesis that cytokine signalling dysregulation affects asthma risk, and raises the possibility that an IL6R antagonist (tocilizumab) may be effective to treat the disease, perhaps in a genotype-dependent manner. Results for the 11q13.5 locus suggest that it directly increases the risk of allergic sensitisation which, in turn, increases the risk of subsequent development of asthma. Larger or more functionally

A Mathematical Theory of Asymptotic Computation.

DTIC Science & Technology

1987-12-01

sie, ft Skabog DeselEe fle WkwMorfbeU.S. evsuinee ROkMl AIR DkEELOPM9 CENTER Gra i A1r ForceW =Sm. NY 13441 -6700 This report haa been reviewed by the... Air Development Center (COTC) kc. ADDRESS (City, State, and ZIPCod.) 7b. ADDRESS (City, State, and ZIP Code) 301A Harris B. Dates Drive Griffiss AFB NY...iicclir ill thle eji’Il~l i . ll tavLlll thi (oi𔃻inv’(l. WVe will Call suich a scquu’niCc’: a trace of lie 11’ _n: -I’ iuon oif ;ill trlaces which

Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA

PubMed Central

Joesting, Jennifer J.; Moon, Morgan L.; Gainey, Stephen J.; Tisza, Brittany L.; Blevins, Neil A.; Freund, Gregory G.

2014-01-01

Objective: Weight-loss is a near societal obsession and many diet programs use significant calorie restriction including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 h fast and how fasting might generate this effect. Design: Mice were allowed ad libitum access to food or had food withheld for 24 h. Expression of the endogenous IL-1 antagonists, IL-1 receptor type 2 (IL-1R2), and IL-1 receptor antagonist (IL-1RA) was determined as were sickness behaviors before and after IL-1β administration. Results: Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver) and IL-1RA (68-fold in liver). Fasted mice were protected from IL-1β-induced weight-loss, hypoglycemia, loss of locomotor, and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1β on IL-1R2 gene expression in adipose tissue and liver (2.6- and 1.6-fold, respectively). Fasting not only increased IL-1RA and IL-1R2 protein 2.5- and 3.2-fold, respectively, in liver but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs) and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14- and 11-fold, respectively. Conclusion: These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation. PMID:25071776

Transplantation rénale au Maroc: l'hémodialysé et son entourage sont-ils suffisamment informés?

PubMed Central

Noto-Kadou-Kaza, Béfa; Sabi, Kossi Akomola; Imangue, Ghislain; Al-Torayhi, Mays Hadi; Amekoudi, Eyram Yoan Makafui; Tsevi, Claude Mawufemo; Zamd, Mohamed; Medkouri, Ghislaine; Benghanem, Mohamed Gharbi; Ramdani, Benyounes

2014-01-01

Introduction La transplantation rénale constitue le traitement idéal de l'insuffisance rénale chronique. Cependant il existe une insuffisance de donneurs contrairement aux receveurs dont le nombre ne cesse de s'accroitre. La méconnaissance de la transplantation par les hémodialysés et leur entourage pourrait être l'une des causes. Notre but était d’évaluer les connaissances et opinions de l'hémodialysé et de son entourage sur la transplantation rénale. Méthodes L'enquête menée en Aout 2013 avait inclus 83 hémodialysés de notre centre et 70 membres de leur entourage. Ils ont été soumis à un questionnaire qui portait sur les thèmes suivants: statut socio-économique, volonté d’être transplanté ou d’être donneur, avantages de la transplantation rénale, point de vue de la religion sur la transplantation. Aucun des individus interrogés n'avait jamais fait l'objet d'une transplantation ou d'un don d'organe. Résultats Parmi 83 hémodialysés on notait 49,4% de femmes avec une moyenne d’âge de 41,4±12 ans. Le niveau socio-économique bas représentait 66,7%. Le manque d'information chez était estimé à 62,7%. Seuls 41% se disaient être candidat à la transplantation rénale mais 12% seulement était inscrit sur la liste d'attente de greffe. La transplantation était estimée plus couteuse que l'hémodialyse par 50,6% des patients et seuls 71,1% estimaient qu'elle offrait une meilleure vie. Pour 20,5%, l'Islam s'opposerait au don cadavérique et pour 10,9% au don vivant. Parmi les 70 membres de l'entourage interrogé il y avait 56,8% de femmes; la moyenne d’âge était de 44,4±10,5 ans. Le niveau économique bas représentait 52,3%. Le manque d'information était estimé à 61,4%. Pour 56,8% la vie serait impossible avec un seul rein. Seuls 13,6% étaient inscrit sur le registre de don. Pour 45,5% l'Islam s'opposerait au don cadavérique. Conclusion Il importe d'intensifier la sensibilisation des hémodialysées et leur famille

Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case–control study

PubMed Central

2012-01-01

Background Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Methods Case–control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Results Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated

Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study.

PubMed

Morales-García, Guadalupe; Falfán-Valencia, Ramcés; García-Ramírez, Román Alejandro; Camarena, Ángel; Ramirez-Venegas, Alejandra; Castillejos-López, Manuel; Pérez-Rodríguez, Martha; González-Bonilla, César; Grajales-Muñíz, Concepción; Borja-Aburto, Víctor; Mejía-Aranguré, Juan Manuel

2012-11-13

Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Case-control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07-1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82-10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48-12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of

Diagnostic value of sTREM-1, IL-8, PCT, and CRP in febrile neutropenia after autologous stem cell transplantation.

PubMed

Michel, C S; Teschner, D; Wagner, E M; Theobald, M; Radsak, Markus P

2017-12-01

Infections and infectious complications are the major cause of morbidity and mortality in febrile neutropenic patients after autologous stem cell transplantation. Laboratory biomarkers are helpful for early identification of critically ill patients and optimal therapy management. Several studies in adult non-neutropenic patients proposed sTREM-1 as a superior biomarker for identification of septic patients as well as a predictor for survival in these patients compared with procalcitonin (PCT), C-reactive protein (CRP), or interleukin-8 (IL-8). Here, to assess the utility of PCT, CRP, IL-8, and sTREM-1 in febrile neutropenia, 44 patients presenting with febrile neutropenia after autologous stem cell transplantation were recruited in a single-center prospective pilot study. We analyzed PCT and CRP as well as IL-8 and sTREM-1 levels pre- and post-transplantation at defined time points. In 20 of 44 patients, concentration of sTREM-1 was under the detection level at appearance of febrile neutropenia. Mean levels of PCT, IL-8, and CRP were significantly increased in infections of critically ill patients who by dysfunction or failure of one or more organs/system depend on survival from advanced instruments of monitoring and therapy. However, all tested biomarkers could not distinguish between presence and absence of bloodstream infection. The combination of the biomarkers PCT and IL-8 achieved a high sensitivity of 90% and specificity of 74% for the identification of serious complications in febrile neutropenia, whereas the combination of CRP and PCT or IL-8 achieved a high sensitivity of 100%, but with the addition of a low specificity of 47or 41%. In conclusion, we found that the measurement of sTREM-1 concentration at presentation of febrile neutropenia is not useful to identify bacterial bloodstream infections and critically ill patients. PCT and IL-8 are useful biomarkers for the early identification of critically ill patients, compared to CRP and sTREM-1 in febrile

A Brief History of IL-1 and IL-1 Ra in Rheumatology.

PubMed

Dayer, Jean-Michel; Oliviero, Francesca; Punzi, Leonardo

2017-01-01

The history of what, in 1979, was called interleukin-1 (IL-1), orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP) (1974) and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE 2 in human synovial cells by a mononuclear cell factor (MCF) (1977). Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra) in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as "inflammasome" have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still's disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet's disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.

Isolation of eukaryotic ribosomal proteins. Purification and characterization of the 60 S ribosomal subunit proteins L4, L5, L7, L9, L11, L12, L13, L21, L22, L23, L26, L27, L30, L33, L35', L37, and L39.

PubMed

Tsurugi, K; Collatz, E; Wool, E G; Lin, A

1976-12-25

The proteins of the large subunit of rat liver ribosomes were separated into seven groups by stepwise elution from carboxymethylcellulose with LiCl at pH 6.5. Seventeen proteins (L4, L5, L7, L9, L11, L12, L13, L21, L22, L23, L26, L27, L30, L33, L35', L37, and L39) were isolated from three of the groups (B60, D60, G60) by ion exchange chromatography on carboxymethylcellulose and by filtration through Sephadex. The amount of protein obtained varied from 0.5 to 15 mg. Eight of the proteins (L9, L11, L13, L21, L22, L35', L37 and L39) had no detectable contamination; the impurities in the others were no greater than 9%. The molecular weight of the proteins was estimated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the amino acid composition was determined.

All Prime Contract Awards by State or Country, Place, and Contractor, FY 87. Part 18. Barrington, Rhode Island-Wooldridge, Tennessee.

DTIC Science & Technology

1987-01-01

INF.. 1967 DIOR/STII-S?/PT-1S USCLSSIFIED F/S 15/5 ML II~ .0ILU284ff" Lm" O3R=) is 36. 2 5I m or w W SECURIrY CLASSIFICATION OF THIS PAGE, F,,7j "Jt...0 U- 0 衲 lZI £1 ()2 woo X1W m . Z~ OW w2 ൴ W 0 ww~o H - "- >LA4c LALA ZC)WO"- U.4 z 1- 0 0 ) -4~Wx D I-I1-40- woI- WWI 2i 1- 0 ).14 - 00)-Z 0Wwl...mm W A~ 00I-O *~" 0f4.1 I I I S I I 0 t l i l ill lot I oi l 111111 0 4)00N~ m 0-4 NC’N~ 4 ~ ~ -4M00I0~4-4.4-4N~lCD1.e@O-I -NMC 41)401- W0 mO--44 -4

Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (γ-EV) Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis.

PubMed

Chee, MacKenzie E; Majumder, Kaustav; Mine, Yoshinori

2017-07-26

Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis. The γ-EV exhibited antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine. γ-EV also reduced the phosphorylation of the signaling proteins JNK and IκBα. We concluded that γ-EV could possess an antisepsis effect against bacterial infection in intestine. This study proposes a signaling mechanism whereby the calcium-sensing receptor (CaSR) allosterically activated by γ-EV stimulates the interaction of β-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and IκBα to suppress inflammatory signaling.

Fine-mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21.

PubMed

Hughes, Travis; Kim-Howard, Xana; Kelly, Jennifer A; Kaufman, Kenneth M; Langefeld, Carl D; Ziegler, Julie; Sanchez, Elena; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Reveille, John D; Martín, Javier; Brown, Elizabeth E; Vilá, Luis M; Alarcón, Graciela S; James, Judith A; Gilkeson, Gary S; Moser, Kathy L; Gaffney, Patrick M; Merrill, Joan T; Vyse, Timothy J; Alarcón-Riquelme, Marta E; Nath, Swapan K; Harley, John B; Sawalha, Amr H

2011-06-01

Genetic association of the IL2/IL21 region at chromosome 4q27 has previously been reported in lupus and a number of autoimmune and inflammatory diseases. This study was undertaken to determine whether this genetic effect could be localized, using a very large cohort of lupus patients and controls. We genotyped 45 tag single-nucleotide polymorphisms (SNPs) across the IL2/IL21 locus in 2 large independent lupus sample sets. We studied a set of subjects of European descent consisting of 4,248 lupus patients and 3,818 healthy controls, and an African American set of 1,569 patients and 1,893 healthy controls. Imputation in 3,004 additional controls from the Wellcome Trust Case Control Consortium was also performed. Genetic association between the genotyped markers was determined, and pairwise conditional analysis was performed to localize the independent genetic effect in the IL2/IL21 locus in lupus. We established and confirmed the genetic association between IL2/IL21 and lupus. Using conditional analysis and transethnic mapping, we localized the genetic effect in this locus to 2 SNPs in high linkage disequilibrium: rs907715 located within IL21 (odds ratio 1.16 [95% confidence interval 1.10-1.22], P=2.17×10(-8)) and rs6835457 located in the 3'-untranslated flanking region of IL21 (odds ratio 1.11 [95% confidence interval 1.05-1.17], P=9.35×10(-5)). Our findings establish the genetic association between lupus and IL2/IL21 with a genome-wide level of significance. Further, our findings indicate that this genetic association within the IL2/IL21 linkage disequilibrium block is localized to IL21. If other autoimmune IL2/IL21 genetic associations are similarly localized, then the IL21 risk alleles would be predicted to operate by a fundamental mechanism that influences the course of a number of autoimmune disease processes. Copyright © 2011 by the American College of Rheumatology.

Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

PubMed Central

Calcagno, Danielle Queiroz; Takeno, Sylvia Santomi; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Chen, Elizabeth Suchi; Araújo, Taíssa Maíra Thomaz; Lima, Eleonidas Moura; Melaragno, Maria Isabel; Demachki, Samia; Assumpção, Paulo Pimentel; Burbano, Rommel Rodriguez; Smith, Marília Cardoso

2016-01-01

AIM To identify common copy number alterations on gastric cancer cell lines. METHODS Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer. PMID:27920471

Interleukin (IL)-23 Stimulates IFN-γ Secretion by CD56bright Natural Killer Cells and Enhances IL-18-Driven Dendritic Cells Activation.

PubMed

Ziblat, Andrea; Nuñez, Sol Y; Raffo Iraolagoitia, Ximena Lucía; Spallanzani, Raúl German; Torres, Nicolás I; Sierra, Jessica M; Secchiari, Florencia; Domaica, Carolina I; Fuertes, Mercedes B; Zwirner, Norberto W

2017-01-01

Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it is also involved in the development of autoimmune diseases. Although immunoregulatory effects of IL-23 on mouse natural killer (NK) cells have been described, the effect of IL-23 on human NK cells remains ill-defined. In this study, we observed that monocytes stimulated with LPS secreted IL-23 and that blockade of this cytokine during monocyte and NK cell coculture led to a diminished production of IFN-γ by NK cells. Accordingly, rIL-23-induced NK cell activation and stimulated IFN-γ production by CD56 bright NK cells. This effect involved MEK1/MEK2, JNK, PI3K, mammalian target of rapamycin, and NF-κB, but not STAT-1, STAT-3, nor p38 MAPK pathways. Moreover, while NK cell-mediated cytotoxicity remained unaltered, antibody-dependent cellular cytotoxicity (ADCC) was enhanced after IL-23 stimulation. In addition, IL-23 displayed a synergistic effect with IL-18 for IFN-γ production by both CD56 bright and CD56 dim NK cells, and this effect was due to a priming effect of IL-23 for IL-18 responsiveness. Furthermore, NK cells pre-stimulated with IL-18 promoted an increase in CD86 expression and IL-12 secretion by DC treated with LPS, and IL-23 potentiated these effects. Moreover, IL-23-driven enhancement of NK cell "helper" function was dependent on NK cell-derived IFN-γ. Therefore, our results suggest that IL-23 may trigger NK cell-mediated "helper" effects on adaptive immunity, shaping T cell responses during different pathological situations through the regulation of DC maturation.

IL-6 and TNF-α salivary levels according to the periodontal status in Portuguese pregnant women.

PubMed

Machado, Vanessa; Mesquita, Maria Fernanda; Bernardo, Maria Alexandra; Casal, Ester; Proença, Luís; Mendes, José João

2018-01-01

Periodontitis is associated with increased concentration of inflammatory markers and saliva has been proposed as a non-invasive diagnostic fluid in oral and systemic diseases. The levels of salivary biomarkers, such as cytokines, could potentially be used to distinguish periodontal healthy individuals from subjects with periodontal disease. The purpose of this study was to characterize the salivary levels of two inflammatory biomarkers associated with periodontitis, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), in order to assess whether these cytokines salivary levels could potentially be used to complement periodontitis pregnant women diagnose. Forty-four pregnant women were distributed into three groups, according to their periodontal status: healthy, mild/moderate periodontitis and severe periodontitis. Unstimulated saliva was collected and analysis of TNF-α and IL-6 salivary levels were performed with Immulite ® . Women with periodontitis exhibited significantly higher levels ( p  = 0.001) of salivary IL-6 and TNF-α compared with the healthy group: 25.1 (±11.2) pg/mL vs. 16.3 (±5.0) pg/mL and 29.7 (±17.2) pg/mL vs. 16.2 (±7.6) pg/mL, approximately 1.5 and 1.8 times more, respectively. Additionally, cytokines were significantly increased ( p  < 0.05) in severe periodontitis compared to periodontal healthy pregnant women. These results revealed that IL-6 and TNF-α salivary biomarkers provide high discriminatory capacity for distinguishing periodontal disease from periodontal health in pregnant women.

Mining and Analyzing Circulation and ILL Data for Informed Collection Development

ERIC Educational Resources Information Center

Link, Forrest E.; Tosaka, Yuji; Weng, Cathy

2015-01-01

The authors investigated quantitative methods of collection use analysis employing library data that are available in ILS and ILL systems to better understand library collection use and user needs. For the purpose of the study, the authors extracted circulation and ILL records from the library's systems using data-mining techniques. By comparing…

IL-6 Receptor Isoforms and Ovarian Cancer Progression

DTIC Science & Technology

2010-10-01

carcinoma cell ines, respectively, were obtained from merican Type Culture Collection (Man- ssas, VA). Cells were maintained in Dul- ecco’s Modified...tien IL6R hist stra (ind trans 010L6R. Cross -reactivity between human rican Journal of Obstetrics & Gynecology 1.e3 a o T 5 g m S D w t R T l a 1 c ( m...allele of IL-6ra (Il6rafl/+) were first crossed with FLPe+/+ mice (38) to delete the FRT-flanked Neo cassette in the targeting vector. Progeny with

Grain dust induces IL-8 production from bronchial epithelial cells: the effect of dexamethasone on IL-8 production.

PubMed

Park, H S; Suh, J H; Kim, H Y; Kwon, O J; Choi, D C

1999-04-01

Recent publications have suggested an active participation of neutrophils to induce bronchoconstriction after inhalation of grain dust (GD). To further understand the role of neutrophils in the pathogenesis of GD-induced asthma, this investigation was designed to determine whether human bronchial epithelial cells could produce IL-8 production and to observe the effect of dexamethasone on IL-8 production. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four concentrations (1 to 200 microg/mL) of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant, which was derived from the culture of PBMC from a GD-induced asthmatic subject under the exposure to 10 microg/mL of GD, and compared with those cultured without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. To evaluate the effect of dexamethasone on IL-8 production, four concentrations (5 to 5000 ng/mL) of dexamethasone were pre-incubated for 24 hours and the same experiments were repeated. There was significant production of IL-8 from bronchial epithelial cells with additions of GD in a dose-dependent manner (P < .05), which was significantly augmented with additions of PBMC supernatant (P < .05) at each concentration. Compared with the untreated sample, pretreatment of dexamethasone could induced a remarkable inhibitions (15% to 55%) of IL-8 production from bronchial epithelial cells in a dose-dependent manner. These results suggest that IL-8 production from bronchial epithelial cells may contribute to neutrophil recruitment occurring in GD-induced airway inflammation. The downregulation of IL-8 production by dexamethasone from bronchial epithelial cells may contribute to the efficacy of this compound in

11. GENERAL VIEW OF STATION 'L', LOOKING SOUTHWEST, BUILDINGS FROM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. GENERAL VIEW OF STATION 'L', LOOKING SOUTHWEST, BUILDINGS FROM LEFT TO RIGHT: LINCOLN SUBSTATION (BUILDING L3), EQUIPMENT BUILDING (BUILDING K), H.P. BOILER ROOM (BUILDING L4), L.P. BOILER ROOM (BUILDING L2), BOILER #16 (BUILDING LB), POWERHOUSE EXTENSION (BUILDING L5), MACHINE SHOP (BUILDING L7) - Portland General Electric Company, Station "L", 1841 Southeast Water Street, Portland, Multnomah County, OR

[Linee guida italiane per il trattamento dell'alcolismo].

PubMed

Ceccanti, Mauro; Iannitelli, Angela; Fiore, Marco

2018-01-01

RIASSUNTO. L'Europa è la regione con il più forte consumo di alcol al mondo, con la più elevata percentuale di malattie totali e morti premature alcol-correlate. In Italia, questo fenomeno coinvolge circa il 13% della popolazione oltre i 18 anni e oltre il 25% dei pazienti ospedalizzati. Sfortunatamente, solo il 5% di questi pazienti vengono riconosciuti come persone affette da disturbo da uso di alcol (DUA). Una scarsa conoscenza della malattia, la mancanza di accesso alle cure e le poche risorse messe a disposizione nella gestione del problema sono tra le principali cause di ritardo nella diagnosi, alla fine con conseguenze cliniche molto più importanti e costose da gestire. Alla luce di ciò, abbiamo deciso di dedicare questo numero speciale della Rivista di psichiatria a una serie di articoli riguardanti le linee guida italiane per il trattamento della dipendenza da alcol. Realizzate in collaborazione con numerosi esperti e importanti società scientifiche italiane come il Centro di Riferimento Alcologico della Regione Lazio (CRARL), la Società Italiana Tossicodipendenze (SITD), la Società italiana per il Trattamento dell'Alcolismo e le sue Complicanze (SITAC), la Società Italiana Psichiatria delle Dipendenze (SIPDip), la Società Italiana Patologie da Dipendenza (SIPaD) e l'Istituto di Biologia Cellulare e Neurobiologia (IBCN-CNR), queste linee guida forniscono agli operatori una serie di raccomandazioni basate su prove di efficacia volte ad aumentare la conoscenza e un uso appropriato dei farmaci per le persone affette da DUA. Con la possibilità di un continuo aggiornamento, l'obiettivo principale di queste linee guida sarà quello di garantire l'omogeneità dei trattamenti e un incremento qualitativo nell'assistenza dei pazienti affetti da DUA, così da ridurre le conseguenze psicosociali e sulla salute pubblica di questa importante malattia psichiatrica.

l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats.

PubMed

Tsai, Wen-Hsin; Wu, Chung-Hsin; Yu, Hong-Jeng; Chien, Chiang-Ting

2017-02-01

Upregulation of substance P (SP) and neurokinin-1 receptor (NK1R) activation induces pro-inflammatory bladder hyperactivity through the PKC/ERK/NF-κB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. l-Theanine is a unique non-protein-forming amino acid present in tea (Camellia sinensis [L.] O. Kuntze) with its antioxidant, anti-inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of l-theanine on SP-induced bladder hyperactivity. In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/poly-(ADP-ribose)-polymerase (PARP), and autophagy-mediated LC3 II expression by Western blot, electrophoretic-mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP-evoked hyperactive bladder. l-Theanine dose-dependently depressed H 2 O 2 and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intra-arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, Caspase 3/PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical l-theanine (15 mg/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP-treated hyperactive bladder. In conclusion, l-theanine through antioxidant and anti-inflammatory actions ameliorates SP

A User’s Guide for the Software Technology Economic Impact Model

DTIC Science & Technology

1991-10-01

Copy 16 oft22 oples U AD-A248 023 \\\\1\\\\\\i\\~\\1\\1\\\\1\\1\\11\\\\\\l~ IDA DOCUMENT D-971 E Tt USER’S GUIDE FOR THE SOFTWARE TECHNOLOGY ECONOMIC IMPACT MODEL I... studied , and they are released by the President of IDA. Group Reports Group Reports record the findings and results of IDA established working groups and...the senior individuals responsible for the project and others as selected by IDA to ensure their high quality and relevance to the problems studied

Word Frequency Analysis MOS: 11H. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

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Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma and COPD

PubMed Central

Doe, Camille; Bafadhel, Mona; Siddiqui, Salman; Desai, Dhananjay; Mistry, Vijay; Rugman, Paul; McCormick, Margaret; Woods, Joanne; May, Richard; Sleeman, Matthew A.; Anderson, Ian K.

2010-01-01

Background: Asthma and COPD are characterized by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease. The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain. Methods: We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects. Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD. Results: The median (interquartile range) IL-17A cells/mm2 submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P = .04). In COPD, IL-17A+ cells/mm2 submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P = .046). IL-17F+ cells/mm2 submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P = .001) but was not increased in subjects with COPD. IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P = .005). The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P < .0001) and was correlated with post-bronchodilator FEV1% predicted (r = −0.5, P = .008) and FEV1/FVC (r = −0.4, P = .04). Conclusions: Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation. PMID:20538817

Word Criticality Analysis. MOS: 26L. Skill Levels 1 & 2.

DTIC Science & Technology

1981-09-01

ch-1l* 94.01 25,1 9, I CO’IL bpi, ICI.MPLFTh $%&I I CIIINU ITV los1 Sol I EGflHI1 ai-1 19,1 12,1 I CI(PiVtf;T~k 303 2.1 a** 7.2 0,2 4.1 90#1 2902 25a2...26.1 3.1 -- ------------- 1. DAYS 6.1 6;4 d I ."~A,4f 283 1li& 601 3. Imk l 11.3. I EXCHANGE los1 11.1 I1 EXPENDABLE 1#1 I F EDERAL --- -----. got

Interleukin (IL)-23 Stimulates IFN-γ Secretion by CD56bright Natural Killer Cells and Enhances IL-18-Driven Dendritic Cells Activation

PubMed Central

Ziblat, Andrea; Nuñez, Sol Y.; Raffo Iraolagoitia, Ximena Lucía; Spallanzani, Raúl German; Torres, Nicolás I.; Sierra, Jessica M.; Secchiari, Florencia; Domaica, Carolina I.; Fuertes, Mercedes B.; Zwirner, Norberto W.

2018-01-01

Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it is also involved in the development of autoimmune diseases. Although immunoregulatory effects of IL-23 on mouse natural killer (NK) cells have been described, the effect of IL-23 on human NK cells remains ill-defined. In this study, we observed that monocytes stimulated with LPS secreted IL-23 and that blockade of this cytokine during monocyte and NK cell coculture led to a diminished production of IFN-γ by NK cells. Accordingly, rIL-23-induced NK cell activation and stimulated IFN-γ production by CD56bright NK cells. This effect involved MEK1/MEK2, JNK, PI3K, mammalian target of rapamycin, and NF-κB, but not STAT-1, STAT-3, nor p38 MAPK pathways. Moreover, while NK cell-mediated cytotoxicity remained unaltered, antibody-dependent cellular cytotoxicity (ADCC) was enhanced after IL-23 stimulation. In addition, IL-23 displayed a synergistic effect with IL-18 for IFN-γ production by both CD56bright and CD56dim NK cells, and this effect was due to a priming effect of IL-23 for IL-18 responsiveness. Furthermore, NK cells pre-stimulated with IL-18 promoted an increase in CD86 expression and IL-12 secretion by DC treated with LPS, and IL-23 potentiated these effects. Moreover, IL-23-driven enhancement of NK cell “helper” function was dependent on NK cell-derived IFN-γ. Therefore, our results suggest that IL-23 may trigger NK cell-mediated “helper” effects on adaptive immunity, shaping T cell responses during different pathological situations through the regulation of DC maturation. PMID:29403472

Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP

PubMed Central

Mazzucchelli, Renata; Hixon, Julie A.; Spolski, Rosanne; Chen, Xin; Li, Wen Qing; Hall, Veronica L.; Willette-Brown, Jami; Hurwitz, Arthur A.; Leonard, Warren J.

2008-01-01

Interleukin-7 (IL-7), a cytokine produced by stromal cells, is required for thymic development and peripheral homeostasis of most major subsets of T cells. We examined whether regulatory T (Treg) cells also required the IL-7 pathway by analyzing IL-7Rα−/− mice. We observed a striking reduction in cells with the Treg surface phenotype (CD4, CD25, GITR (glucocorticoid-induced tumor necrosis factor [TNF]-like receptor), CD45RB, CD62L, CD103) or intracellular markers (cytotoxic T-lymphocyte–associated antigen-4, CTLA-4, and forkhead box transcription factor 3, Foxp3). Foxp3 transcripts were virtually absent in IL-7Rα−/− lymphoid tissues, and no Treg cell suppressive activity could be detected. There are 2 known ligands for IL-7Rα: IL-7 itself and thymic stromal lymphopoietin (TSLP). Surprisingly, mice deficient in IL-7 or the other chain of the TSLP receptor (TSLPR) developed relatively normal numbers of Treg cells. Combined deletion of IL-7 and TSLP receptor greatly reduced Treg cell development in the thymus but was not required for survival of mature peripheral Treg cells. We conclude that Treg cells, like other T cells, require signals from the IL-7 receptor, but unlike other T cells, do not require IL-7 itself because of at least partially overlapping actions of IL-7 and TSLP for development of Treg cells. PMID:18664628

Interleukin (IL)-18 Binding Protein Deficiency Disrupts Natural Killer Cell Maturation and Diminishes Circulating IL-18

PubMed Central

Harms, Robert Z.; Creer, Austin J.; Lorenzo-Arteaga, Kristina M.; Ostlund, Katie R.; Sarvetnick, Nora E.

2017-01-01

The cytokine interleukin (IL)-18 is a crucial amplifier of natural killer (NK) cell function. IL-18 signaling is regulated by the inhibitory effects of IL-18 binding protein (IL-18BP). Using mice deficient in IL-18BP (IL-18BPKO), we investigated the impact of mismanaged IL-18 signaling on NK cells. We found an overall reduced abundance of splenic NK cells in the absence of IL-18BP. Closer examination of NK cell subsets in spleen and bone marrow using CD27 and CD11b expression revealed that immature NK cells were increased in abundance, while the mature population of NK cells was reduced. Also, NK cells were polarized to greater production of TNF-α, while dedicated IFN-γ producers were reduced. A novel subset of IL-18 receptor α− NK cells contributed to the expansion of immature NK cells in IL-18BPKO mice. Splenocytes cultured with IL-18 resulted in alterations similar to those observed in IL-18BP deficiency. NK cell changes were associated with significantly reduced levels of circulating plasma IL-18. However, IL-18BPKO mice exhibited normal weight gain and responded to LPS challenge with a >10-fold increase in IFN-γ compared to wild type. Finally, we identified that the source of splenic IL-18BP was among dendritic cells/macrophage localized to the T cell-rich regions of the spleen. Our results demonstrate that IL-18BP is required for normal NK cell abundance and function and also contributes to maintaining steady-state levels of circulating IL-18. Thus, IL-18BP appears to have functions suggestive of a carrier protein, not just an inhibitor. PMID:28900426

A Novel IL-17 Dependent Mechanism of Cross Protection: Respiratory Infection with Mycoplasma Protects Against a Secondary Listeria Infection

PubMed Central

Sieve, Amy N.; Meeks, Karen D.; Bodhankar, Sheetal; Lee, Suheung; Kolls, Jay K.; Simecka, Jerry W.; Berg, Rance E.

2009-01-01

Summary Immune responses to pathogens occur within the context of current and previous infections. Cross protection refers to the phenomena where infection with a particular pathogen provides enhanced resistance to a subsequent unrelated pathogen in an antigen independent manner. Proposed mechanisms of antigen-independent cross protection have involved the secretion of IFN-γ, which activates macrophages thus providing enhanced innate immunity against the secondary viral or bacterial pathogen. Here we provide evidence that a primary infection with the chronic respiratory pathogen, Mycoplasma pulmonis, provides a novel form of cross protection against a secondary infection with Listeria monocytogenes that is not mediated by IFN-γ, but instead relies upon IL-17 and mobilization of neutrophils. Mice infected with M. pulmonis have enhanced clearance of L. monocytogenes from the spleen and liver which is associated with increased numbers of Gr-1+CD11b+ cells and higher levels of IL-17. This enhanced clearance of L. monocytogenes was absent in mice depleted of Gr-1+ cells or in mice deficient in the IL-17 receptor. Additionally, both the IL-17 receptor and neutrophils were essential for optimal clearance of M. pulmonis. Thus, a natural component of the immune response directed against M. pulmonis was able to enhance clearance of L. monocytogenes. PMID:19180464

Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

PubMed

Yu, Xuelian; Zhang, Xi; Zhao, Baihui; Wang, Jiayu; Zhu, Zhaokui; Teng, Zheng; Shao, Junjie; Shen, Jiaren; Gao, Ye; Yuan, Zhengan; Wu, Fan

2011-01-01

The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity. We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression. A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further detailed investigations.

Intensive Cytokine induction in Pandemic H1N1 Influenza Virus Infection Accompanied by Robust Production of IL-10 and IL-6

PubMed Central

Yu, Xuelian; Zhang, Xi; Zhao, Baihui; Wang, Jiayu; Zhu, Zhaokui; Teng, Zheng; Shao, Junjie; Shen, Jiaren; Gao, Ye; Yuan, Zhengan; Wu, Fan

2011-01-01

Background The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity. Methods and Principal Findings We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression. Conclusion and Significance A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further

Coagulin-L ameliorates TLR4 induced oxidative damage and immune response by regulating mitochondria and NOX-derived ROS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, Sukka Santosh

Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10 μM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide. Mechanistically, coagulin-L abrogated LPS induced total and mitochondrialmore » ROS generation, NOX2, NOX4 mRNA expression, IRAK and MAPK (p38, JNK, ERK) activation. Coagulin-L also attenuated IκBα degradation, which prevented NFκB downstream iNOS expression and pro-inflammatory cytokine release. Furthermore, coagulin-L (10, 25, 50 mg/kg, p.o.), undermined the LPS (10 mg/kg, i.p.) induced endotoxemia response in mice as evinced from diminished cytokine release, nitric oxide, aortic p38 MAPK activation and endothelial tissue impairment besides suppressing NOX2 and NOX4 expression in liver and aorta. Moreover, coagulin-L also alleviated the ROS mediated oxidative damage which was assessed through protein carbonyl, lipid hydroperoxide, 8-isoprostane and 8-hydroxy-2-deoxyguanosine quantification. To extend, coagulin-L also suppressed carrageenan-induced paw edema and thioglycollate-induced peritonitis in mice. Therefore, coagulin-L can be of therapeutic importance in pathological conditions induced by oxidative damage. - Highlights: • Coagulin-L demonstrates immunomodulatory effects in vivo and in vitro by modulating ROS. • Coagulin-L modulates TH1/TH2/TH17 immunokines. • Coagulin-L exerts immunomodulatory effect by regulating TLR4-IRAK- ROS

The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression.

PubMed

Chen, Miao-Fen; Chen, Ping-Tsung; Chen, Wen-Cheng; Lu, Ming-Shian; Lin, Paul-Yang; Lee, Kuan Der

2016-02-16

The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival.As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.

Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury.

PubMed

Aisiku, Imo P; Yamal, Jose-Miguel; Doshi, Pratik; Benoit, Julia S; Gopinath, Shankar; Goodman, Jerry C; Robertson, Claudia S

2016-09-15

Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. NCT00313716 registered 4/2006.

Split2 Protein-Ligation Generates Active IL-6-Type Hyper-Cytokines from Inactive Precursors.

PubMed

Moll, Jens M; Wehmöller, Melanie; Frank, Nils C; Homey, Lisa; Baran, Paul; Garbers, Christoph; Lamertz, Larissa; Axelrod, Jonathan H; Galun, Eithan; Mootz, Henning D; Scheller, Jürgen

2017-12-15

Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses. To enable tailor-made generation of Hyper-cytokines, we developed inactive split-cytokine-precursors adapted for posttranslational reassembly by split-intein mediated protein trans-splicing (PTS). We identified cutting sites within IL-6 (E 134 /S 135 ) and IL-11 (G 116 /S 117 ) and obtained inactive split-Hyper-IL-6 and split-Hyper-IL-11 cytokine precursors. After fusion with split-inteins, PTS resulted in reconstitution of active Hyper-cytokines, which were efficiently secreted from transfected cells. Our strategy comprises the development of a background-free cytokine signaling system from reversibly inactivated precursor cytokines.

The immunologic and antioxidant effects of L-phenylalanine on the uterine implantation of mice embryos during early pregnancy.

PubMed

Dong, Yulan; Bai, Yongping; Liu, Guanhui; Wang, Zixu; Cao, Jing; Chen, Yaoxing; Yang, Hongliang

2014-10-01

L-phenylalanine (L-PHE) is a synthetic precursor of catecholamines. Because it cannot be synthesised by an organism, it must be absorbed from the environment. Despite the wide use of L-PHE, whether L-PHE has a negative impact on embryo implantation and development is poorly understood. This study attempted to determine the roles of L-PHE in embryo implantation and development and in the immune response and antioxidant status of the uterus in early pregnancy mice injected intraperitoneally with 320 mg/kg L-PHE. The embryo number of treated mice decreased by 57.6%, and the size of their embryos was reduced by 2.8% (P⟩0.05) along the long diameter and 11.9% (P⟨0.05) along the short diameter at E9 compared with control mice. In addition, L-PHE significantly suppressed B lymphocyte proliferation. L-PHE increased IL-2 secretion but decreased the IL-4 concentration, thereby up-regulating the ratio of IL-2/IL-4 to 1.37-8.45. An analysis of the oxidant and antioxidant status showed that, compared with the control mice, the level of superoxide dismutase activity decreased by 21.54-39.94% and the glutathione peroxidase activity decreased by 15.27-18.96% among the L-PHE-treated mice at E1-E9. However, the malonaldehyde content increased by 14.29%-90.11% among the L-PHE-treated mice. Therefore, L-PHE impaired embryo implantation by disrupting cytokine-based immunity and oxidative stress in the uterus.

IL-17 induces osteoclastogenesis from human monocytes alone in the absence of osteoblasts, which is potently inhibited by anti-TNF-alpha antibody: a novel mechanism of osteoclastogenesis by IL-17.

PubMed

Yago, Toru; Nanke, Yuki; Ichikawa, Naomi; Kobashigawa, Tsuyoshi; Mogi, Makio; Kamatani, Naoyuki; Kotake, Shigeru

2009-11-01

IL-17 is a proinflammatory cytokine crucial for osteoclastic bone resorption in the presence of osteoblasts or synoviocytes in rheumatoid arthritis. However, the role of IL-17 in osteoclastogenesis from human monocytes alone remains unclear. Here, we investigated the role of IL-17 in osteoclastogenesis from human monocytes alone and the direct effect of infliximab on the osteoclastogenesis induced by IL-17. Human peripheral blood mononuclear cells (PBMC) were cultured for 3 days with M-CSF. After non-adherent cells were removed, IL-17 was added with either infliximab or osteoprotegerin (OPG). Seven days later, adherent cells were stained for vitronectin receptor. On the other hand, CD11b-positive monocytes purified from PBMC were also cultured and stained as described above. CD11b-positive cells were cultured with TNF-alpha and receptor activator of NF-kappaB ligand (RANKL). In the cultures of both adherent cells and CD11b-positive cells, IL-17 dose-dependently induced osteoclastogenesis in the absence of soluble-RANKL. OPG or infliximab inhibited IL-17-induced osteoclastogenesis. Interestingly, in the culture of CD11b-positive cells, the osteoclastogenesis was more potently inhibited by infliximab than by OPG. TNF-alpha and RANKL synergistically induced osteoclastogenesis. The present study clearly demonstrated the novel mechanism by which IL-17 directly induces osteoclastogenesis from human monocytes alone. In addition, infliximab potently inhibits the osteoclastogenesis directly induced by IL-17. (c) 2009 Wiley-Liss, Inc.

Changes in photosynthetic performance and antioxidative strategies during maturation of Norway maple (Acer platanoides L.) leaves.

PubMed

Lepeduš, Hrvoje; Gaća, Vlatka; Viljevac, Marija; Kovač, Spomenka; Fulgosi, Hrvoje; Simić, Domagoj; Jurković, Vlatka; Cesar, Vera

2011-04-01

Different structural and functional changes take place during leaf development. Since some of them are highly connected to oxidative metabolism, regulation of reactive oxygen species (ROS) abundance is required. Most of the reactive oxygen species ROS in plant cells are produced in chloroplasts as a result of highly energetic reactions of photosynthesis. The aim of our study was to examine the changes in concentration of oxidative stress parameters (TBARS - thiobarbituric acid-reacting substances and protein carbonyls) as well as antioxidative strategies during development of maple (Acer platanoides L.) leaves in the light of their enhanced photosynthetic performance. We reveal that biogenesis of the photosynthetic apparatus during maple leaf maturation corresponded with oxidative damage of lipids, but not proteins. In addition, antioxidative responses in young leaves differed from that in older leaves. Young leaves had high values of non-photochemical quenching (NPQ) and catalase (CAT, EC 1.11.1.6) activity which declined during the maturation process. Developing leaves were characterized by an increase in TBARS level, the content of non-enzymatic antioxidants as well as ascorbate peroxidase activity (APX, EC 1.11.1.11), while the content of protein carbonyls decreased with leaf maturation. Fully developed leaves had the highest lipid peroxidation level accompanied by a maximum in ascorbic acid content and superoxide dismutase activity (SOD, EC1.15.1.1). These observations imply completely different antioxidative strategies during leaf maturation enabling them to perform their basic function. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer: Analysis of Clinical Samples and BMTP-11 Preclinical Activity.

PubMed

Cardó-Vila, Marina; Marchiò, Serena; Sato, Masanori; Staquicini, Fernanda I; Smith, Tracey L; Bronk, Julianna K; Yin, Guosheng; Zurita, Amado J; Sun, Menghong; Behrens, Carmen; Sidman, Richard L; Lee, J Jack; Hong, Waun K; Wistuba, Ignacio I; Arap, Wadih; Pasqualini, Renata

2016-08-01

We previously isolated an IL-11-mimic motif (CGRRAGGSC) that binds to IL-11 receptor (IL-11R) in vitro and accumulates in IL-11R-expressing tumors in vivo. This synthetic peptide ligand was used as a tumor-targeting moiety in the rational design of BMTP-11, which is a drug candidate in clinical trials. Here, we investigated the specificity and accessibility of IL-11R as a target and the efficacy of BMTP-11 as a ligand-targeted drug in lung cancer. We observed high IL-11R expression levels in a large cohort of patients (n = 368). In matching surgical specimens (i.e., paired tumors and nonmalignant tissues), the cytoplasmic levels of IL-11R in tumor areas were significantly higher than in nonmalignant tissues (n = 36; P = 0.003). Notably, marked overexpression of IL-11R was observed in both tumor epithelial and vascular endothelial cell membranes (n = 301; P < 0.0001). BMTP-11 induced in vitro cell death in a representative panel of human lung cancer cell lines. BMTP-11 treatment attenuated the growth of subcutaneous xenografts and reduced the number of pulmonary tumors after tail vein injection of human lung cancer cells in mice. Our findings validate BMTP-11 as a pharmacologic candidate drug in preclinical models of lung cancer and patient-derived tumors. Moreover, the high expression level in patients with non-small cell lung cancer is a promising feature for potential translational applications. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

High glucose intake and glycaemic level in critically ill neonates with inherited metabolic disorders of intoxication.

PubMed

Grimaud, Marion; de Lonlay, Pascale; Dupic, Laurent; Arnoux, Jean-Baptiste; Brassier, Anais; Hubert, Philippe; Lesage, Fabrice; Oualha, Mehdi

2016-06-01

To investigate glycaemic levels in critically ill neonates with inherited metabolic disorders of intoxication. Thirty-nine neonates with a median age of 7 days (0-24) were retrospectively included (urea cycle disorders (n = 18), maple syrup disease (n = 13), organic acidemias (n = 8)). Twenty-seven neonates were intubated, 21 were haemodialysed and 6 died. During the first 3 days, median total and peak blood glucose (BG) levels were 7.1 mmol/L (0.9-50) and 10 mmol/L (5.1-50), respectively. The median glucose intake rate was 11 mg/kg/min (2.7-15.9). Fifteen and 23 neonates exhibited severe hyperglycaemia (≥2 BG levels >12 mmol/L) and mild hyperglycaemia (≥2 BG levels >7 and ≤12 mmol/L), respectively. Glycaemic levels and number of hyperglycaemic neonates decreased over the first 3 days (p < 0.001) while total glucose intake rate was stable (p = 0.11). Enteral route of glucose intake was associated with a lower number of hyperglycaemic neonates (p = 0.04) and glycaemic level (p = 0.02). Hyperglycaemia is common in critically ill neonates receiving high glucose intake with inherited metabolic disorders of intoxication. Physicians should decrease the rate of total glucose intake and begin enteral feeding as quickly as possible in cases of persistent hyperglycaemia. • The risk of hyperglycaemia in the acute phase of critical illness is high. What is New: • Hyperglycaemia is common in the initial management of critically ill neonates with inherited metabolic disorders of intoxication receiving high glucose intake.

Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1beta after live yellow fever vaccination.

PubMed

Hacker, U T; Erhardt, S; Tschöp, K; Jelinek, T; Endres, S

2001-09-01

The inflammatory response in infectious and autoimmune diseases is regulated by the balance between pro- and anti-inflammatory cytokines. The IL-1 complex contains polymorphic genes coding for IL-1alpha, IL-1beta and IL-1Ra. The IL-1Ra (variable number of tanden repeat) VNTR polymorphism has been shown to influence the capacity to produce IL-1beta and IL-1Ra after in vitro stimulation. Allele 2 of this polymorphism is associated with a number of inflammatory diseases. To determine the impact of the IL-1Ra polymorphism on in vivo human cytokine synthesis, we used a yellow fever vaccination model for the induction of cytokine synthesis in healthy volunteers. Two different yellow fever vaccines were used. After administration of the RKI vaccine (34 volunteers), plasma TNF-alpha concentration increased from 13.4 +/- 0.9 pg/ml to 23.3 +/- 1.1 pg/ml (P < 0.001), and plasma IL-1Ra concentration increased from 308 +/- 25 pg/ml to 1019 +/- 111 pg/ml (P < 0.001), on day 2. Using Stamaril vaccine, no increase in the plasma concentrations of either TNF-alpha or IL-1Ra could be detected (n = 17). Only the RKI vaccine induced TNF-alpha synthesis after in vitro stimulation of MNC. Carriers of allele 2 of the IL-1Ra polymorphism had increased baseline concentrations of IL-1Ra (350 +/- 32 pg/ml) compared with non-carriers (222 +/- 18 pg/ml, P < 0.001), and decreased concentrations of IL-1beta (0.9 +/- 0.2 pg/ml for carriers versus 2.8 +/- 0.7 pg/ml for non-carriers, P = 0.017). After yellow fever vaccination (RKI vaccine), no significant differences in the increase of IL-1Ra plasma levels were detected between carriers and non-carriers of allele 2 of the IL-1Ra gene polymorphism. This is the first study to examine the influence of this genetic polymorphism on in vivo-induced human IL-1beta and IL-1Ra synthesis. Baseline concentrations of IL-1Ra and IL-1beta were significantly influenced by the IL-1Ra polymorphism. No influence of the IL-1Ra polymorphism on the in vivo

Vitamin D deficiency and high serum IL-6 concentration as risk factors for tubal factor infertility in Chinese women.

PubMed

Chen, Weiwei; Jiao, Xianting; Zhang, Jun; Wang, Lei; Yu, Xiaodan

2018-05-01

The aim of this study was to investigate the relationship between 25-hydroxyvitamin-D [25(OH)D] and female infertility and to further explore the role of inflammatory cytokines. We recruited 356 infertile women diagnosed with tubal factor infertility (TFI) or polycystic ovary syndrome (PCOS) or endometriosis, as well as 180 fertile women. Serum concentrations of 25(OH)D, interleukin (IL)-6, IL-1 β, and interferon-α were measured. The 25(OH)D concentration in TFI women was the lowest (16.9 ng/mL) and was significantly different from that in the fertile women (19.4 ng/mL; P <0.05)]; whereas women with TFI had higher IL-6 concentrations. After adjusting for confounders, 25(OH)D deficiency presented a risk factor for TFI (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.5-11.3). There was a dose-effect relation between IL-6 tertiles and TFI: the higher the IL-6, the higher the risk for TFI (middle versus low: OR, 3.7; 95% CI, 1.5-9.5; high versus low: OR, 13.2; 95% CI, 4.8-36.4). IL-6 showed a negative correlation with 25(OH)D (r = -0.19). Women with both high IL-6 and low 25(OH)D had the highest risk for TFI (OR, 10.6; 95% CI, 4.2-26.3). Both vitamin D deficiency and high serum IL-6 concentration are risk factors for TFI. Serum 25(OH)D concentration was significantly and negatively correlated with serum IL-6. There was an interaction between IL-6 and 25(OH)D for the risk for TFI-related infertility. We hypothesized that vitamin D might reduce the risk for TFI through suppressing the production of IL-6. Copyright © 2017 Elsevier Inc. All rights reserved.

Chicago, Burlington, & Quincy R.R car works aurora, ILL. Photocopy ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Chicago, Burlington, & Quincy R.R car works aurora, ILL. Photocopy of an undated lithograph based on an ambrotype by D.C. Pratt, C. 1857 - Chicago, Burlington & Quincy Railroad, Roundhouse & Shops, Broadway & Spring Streets, Aurora, Kane County, IL

Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11.

PubMed

Christie, Deborah; Romano, Gabriella; Barnes, Jacqueline; Madge, Nicola; Nicholas, David B; Koot, Hans M; Armstrong, Daniel F; Shevlin, Mark; Kantaris, Xenya; Khatun, Hasina; Sutcliffe, Alastair G

2012-01-01

The objective of this study was to explore young children's views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5-11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge.

Design of the AFGL Prototype Long Baseline Tiltmeter.

DTIC Science & Technology

1985-08-29

331 row Design of the AFGL Prototype Long Baseline Tiltmeter Ik KENNETH 0. POHLIG, ILt, USAF SCHARINE KIRCHOFF ~ 29 August 1985 ilL Approved for... Tiltmeter 9ATRT,rI,f,’, Kent 0. ,se." 11A de’. I, , andIl ,,,,’.cho, Shr seso eliltrCoic s andEC ineEae and -1- res th oue cssema isd inlded. Reslt ofoc...aubr twoda ts arer described. theeina prototyp elnba lie tiltmetershows ah hdpedneupns temper~ature variation. Trhis must be eliminated if the tiltmeter

IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation.

PubMed

Betts, Brian C; Pidala, Joseph; Kim, Jongphil; Mishra, Asmita; Nishihori, Taiga; Perez, Lia; Ochoa-Bayona, Jose Leonel; Khimani, Farhad; Walton, Kelly; Bookout, Ryan; Nieder, Michael; Khaira, Divis K; Davila, Marco; Alsina, Melissa; Field, Teresa; Ayala, Ernesto; Locke, Frederick L; Riches, Marcie; Kharfan-Dabaja, Mohamed; Fernandez, Hugo; Anasetti, Claudio

2017-05-01

Graft- versus -host disease (GvHD) remains a major cause of transplant-related mortality. Interleukin-2 (IL-2) plus sirolimus (SIR) synergistically reduces acute GvHD in rodents and promotes regulatory T cells. This phase II trial tested the hypothesis that IL-2 would facilitate STAT5 phosphorylation in donor T cells, expand regulatory T cells, and ameliorate GvHD. Between 16 th April 2014 and 19 th December 2015, 20 patients received IL-2 (200,000 IU/m 2 thrice weekly, days 0 to +90) with SIR (5-14 ng/mL) and tacrolimus (TAC) (3-7 ng/mL) after HLA-matched related or unrelated allogeneic hematopoietic cell transplantation (HCT). The study was designed to capture an increase in regulatory T cells from 16.0% to more than 23.2% at day +30. IL-2/SIR/TAC significantly increased regulatory T cells at day +30 compared to our published data with SIR/TAC (23.8% vs. 16.0%, P =0.0016; 0.052 k/uL vs. 0.037 k/uL, P =0.0163), achieving the primary study end point. However, adding IL-2 to SIR/TAC led to a fall in regulatory T cells by day +90 and did not reduce acute or chronic GvHD. Patients who discontinued IL-2 before day +100 showed a suggested trend toward less grade II-IV acute GvHD (16.7% vs. 50%, P =0.1475). We surmise that the reported accumulation of IL-2 receptors in circulation over time may neutralize IL-2, lead to progressive loss of regulatory T cells, and offset its clinical efficacy. The amount of phospho-STAT3 + CD4 + T cells correlated with donor T-cell activation and acute GvHD incidence despite early T-cell STAT5 phosphorylation by IL-2. Optimizing IL-2 dosing and overcoming cytokine sequestration by soluble IL-2 receptor may sustain lasting regulatory T cells after transplantation. However, an approach to target STAT3 is needed to enhance GvHD prevention. ( clinicaltrials.gov identifier: 01927120 ). Copyright© Ferrata Storti Foundation.

The effect of additional brain injury on systemic interleukin (IL)-10 and IL-13 levels in trauma patients.

PubMed

Hensler, T; Sauerland, S; Riess, P; Hess, S; Helling, H J; Andermahr, J; Bouillon, B; Neugebauer, E A

2000-10-01

Besides interleukin (IL)-10, accumulating evidence from in vitro studies has indicated a strong antiinflammatory capacity for IL-13. A prospective clinical study was undertaken to assess the influence of additional brain injury on systemic IL-10 and IL-13 levels as markers for the antiinflammatory state in trauma patients. The course of IL-10 and IL-13 plasma levels from 32 patients with an isolated severe head trauma (SHT), 50 patients with multiple injuries and additional SHT and 39 patients with multiple injuries without SHT was detected using ELISA-technique. Blood samples from 37 healthy blood donors were analysed for control. IL-10 levels were significantly elevated in all 3 injury groups within 3 h after trauma. The lowest initial release was detected in patients with an isolated SHT (Injury severity score; ISS: 18.1 +/- 5.6). No difference could be demonstrated for the IL-10 levels from multiple injured patients with (ISS: 35.3 +/- 9.6) or without additional SHT (ISS: 25.5 +/- 11.7), though there were relevant differences in the ISS. In contrast, the IL-13 plasma levels were not elevated systemically after trauma. IL-10 but not IL-13 is a detectable antiinflammatory marker in trauma patients with or without brain injury and to a minor degree in patients with an isolated SHT.

Defense.gov Special Report: Veterans Day 2011

Science.gov Websites

Department of Defense Submit Search Veterans Day 2011 - Honoring our Nation's Veterans - 11.11.11 Sept. 26 deserve our country's gratitude - not just on Veterans Day, but every day." Defense Secretary Leon E . Story Leaders Participate in Vets Day Events WASHINGTON, Nov. 11, 2011 - Today's Arlington National

Multiple lipopolysaccharide (LPS) injections alter interleukin 6 (IL-6), IL-7, IL-10 and IL-6 and IL-7 receptor mRNA in CNS and spleen.

PubMed

Szot, Patricia; Franklin, Allyn; Figlewicz, Dianne P; Beuca, Timothy Petru; Bullock, Kristin; Hansen, Kim; Banks, William A; Raskind, Murray A; Peskind, Elaine R

2017-07-04

Neuroinflammation is proposed to be an important component in the development of several central nervous system (CNS) disorders including depression, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, exactly how neuroinflammation leads to, or contributes to, these central disorders is unclear. The objective of the study was to examine and compare the expression of mRNAs for interleukin-6 (IL-6), IL-7, IL-10 and the receptors for IL-6 (IL-6R) and IL-7 (IL-7R) using in situ hybridization in discrete brain regions and in the spleen after multiple injections of 3mg/kg lipopolysaccharide (LPS), a model of neuroinflammation. In the spleen, LPS significantly elevated IL-6 mRNA expression, then IL-10 mRNA, with no effect on IL-7 or IL-7R mRNA, while significantly decreasing IL-6R mRNA expression. In the CNS, LPS administration had the greatest effect on IL-6 and IL-6R mRNA. LPS increased IL-6 mRNA expression only in non-neuronal cells throughout the brain, but significantly elevated IL-6R mRNA in neuronal populations, where observed, except the cerebellum. LPS resulted in variable effects on IL-10 mRNA, and had no effect on IL-7 or IL-7R mRNA expression. These studies indicate that LPS-induced neuroinflammation has substantial but variable effects on the regional and cellular patterns of CNS IL-6, IL-7 and IL-10, and for IL-6R and IL-7R mRNA expression. It is apparent that administration of LPS can affect non-neuronal and neuronal cells in the brain. Further research is required to determine how CNS inflammatory changes associated with IL-6, IL-10 and IL-6R could in turn contribute to the development of CNS neurological disorders. Published by Elsevier Ltd.

[How do mentally ill parents evaluate their children's quality of life? Associations with the parent's illness and family functioning].

PubMed

Pollak, Eva; Bullinger, Monika; Jeske, Jana; Wiegand-Grefe, Silke

2008-01-01

To assess health-related quality of life (hrQoL) of children with a mentally ill parent, and its associations with the parent's illness (diagnoses, severity of disease, current symptoms) and family functioning, 51 mentally ill parents rated their children's hrQoL using the KINDL-R, a multidimensional hrQoL questionnaire for children. Parents rated their current psychiatric symptoms on the SCL-14 (Symptom Checklist-14) and family functioning on the FB-A ("Familienbögen"). The parents' therapists (psychologists or psychiatrists) provided psychiatric diagnoses as well as global ratings of disease severity (CGI) and patient's family functioning. Compared to the general population, parents rated their children's hrQoL significantly lower concerning the dimensions "Psychological Well-Being" and "Family': HrQoL ratings were moderately correlated with the parent's current depressive symptoms and moderately to highly correlated with family functioning from the parent's perspective. Lower depression severity and higher family functioning were associated with higher hrQoL ratings. Parents with affective disorders rated their children's hrQoL significantly lower than did parents with a diagnosis of substance abuse. Results show the importance of family functioning for parents' view of children's hrQoL and the influence of psychiatric symptoms on ill parents' reports. These findings are in line with previous results concerning potential psychological and behavioural problems in children of mentally ill parents. Family interventions and multi-informant assessment should be used in this high-risk group.

Early induction of IL-1 receptor antagonist (IL-1Ra) in infants and children undergoing surgery.

PubMed Central

O Nualláin, E M; Puri, P; Reen, D J

1993-01-01

The cytokine response to injury or trauma is of interest in terms of both its mediation of the acute phase response and its possible relation to the immunological depression observed after major surgery. In this study, the production of cytokines IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and the naturally occurring inhibitor of IL-1, IL-1Ra, have been investigated in infants and children undergoing Swenson's pull-through operation for Hirschsprung's disease. Samples of peripheral blood were taken before, during and after surgery for the measurement of cytokines. IL-1Ra levels increased significantly (P < 0.01) at 2 h after commencement of surgery, with maximal levels for individual patients being attained between 3 h and 5 h (range 7.6-67.9 ng/ml). The mean level of IL-1Ra was maximal (26.2 ng/ml) at 5 h and returned to baseline levels between 24 h and 72 h. There were no changes observed in the circulating levels of IL-1 beta in nine out of 11 patients following commencement of surgery. TNF-alpha levels did not increase in any of the patients studied. IL-6 levels increased significantly (P < 0.02) 3 h after commencement of surgery, reaching maximum concentrations at 24 h (range 20-670 pg/ml), with levels falling between 48 h and 72 h. This study demonstrates, in vivo, the independent induction of IL-1Ra without a concomitant increase of IL-1 beta levels after major surgery. It also shows that IL-1Ra is the earliest cytokine produced in response to surgical stress. PMID:8348747

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis.

PubMed

Biton, Jérôme; Khaleghparast Athari, Sara; Thiolat, Allan; Santinon, François; Lemeiter, Delphine; Hervé, Roxane; Delavallée, Laure; Levescot, Anais; Roga, Stéphane; Decker, Patrice; Girard, Jean-Philippe; Herbelin, André; Boissier, Marie-Christophe; Bessis, Natacha

2016-09-01

IL-33 is strongly involved in several inflammatory and autoimmune disorders with both pro- and anti-inflammatory properties. However, its contribution to chronic autoimmune inflammation, such as rheumatoid arthritis, is ill defined and probably requires tight regulation. In this study, we aimed at deciphering the complex role of IL-33 in a model of rheumatoid arthritis, namely, collagen-induced arthritis (CIA). We report that repeated injections of IL-33 during induction (early) and during development (late) of CIA strongly suppressed clinical and histological signs of arthritis. In contrast, a late IL-33 injection had no effect. The cellular mechanism involved in protection was related to an enhanced type 2 immune response, including the expansion of eosinophils, Th2 cells, and type 2 innate lymphoid cells, associated with an increase in type 2 cytokine levels in the serum of IL-33-treated mice. Moreover, our work strongly highlights the interplay between IL-33 and regulatory T cells (Tregs), demonstrated by the dramatic in vivo increase in Treg frequencies after IL-33 treatment of CIA. More importantly, Tregs from IL-33-treated mice displayed enhanced capacities to suppress IFN-γ production by effector T cells, suggesting that IL-33 not only favors Treg proliferation but also enhances their immunosuppressive properties. In concordance with these observations, we found that IL-33 induced the emergence of a CD39(high) Treg population in a ST2L-dependent manner. Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development. Copyright © 2016 by The American Association of Immunologists, Inc.

Analysis of IL-6, IL-10 and NF-κB Gene Polymorphisms in Aggressive and Chronic Periodontitis.

PubMed

Toker, Hülya; Görgün, Emine Pirim; Korkmaz, Ertan Mahir

2017-06-01

Pro-inflammatory cytokines, interleukin-6 (IL-6), demonstrated to be suppressed by interleukin-10 (IL-10) are known to be regulated by the transcription factor nuclear factor-κB(NF-κB). The aim of this study was to ascertain the association between genetic polymorphism of these genes (IL-6(-174), IL-10(-597) and NF-κB1-94ins/del)) and chronic/aggressive periodontitis. Forty-five patients with chronic periodontitis (CP), 58 patients with aggressive periodontitis (AP) and 38 periodontally healthy subjects were included in this study. Genomic DNA was isolated from whole blood samples. The NF-κB, IL-6, and IL-10 polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among subjects for the ins/ins genotypes of NF-κB1 gene, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis group than in healthy controls (p=0.023). A statistically significant difference in genotyping frequencies between AP group and healthy controls was observed for the IL-6 gene. The AA genotype of IL-10 was overrepresented in CP and AP groups compared to healthy controls (OR=9.93, 95% CI: 2.11-46.7, OR=5.7, 95% CI: 1.22-26.89, respectively). Within the limits of this study, it can be concluded that the IL-10 (-597) AA genotype is associated with susceptibility to chronic/aggressive periodontitis and IL-6 (-174) GG genotypes and G allele seems to be associated with aggressive periodontitis. Clinical relevance: The results of the current study indicate that IL-6 and IL-10 genotypes seem to be associated with aggressive periodontitis. Also, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis subjects with carrying NF-κB1 ins/ins genotypes. Copyright© by the National Institute of Public Health, Prague 2017

Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy

PubMed Central

Murugan, Raghavan; Wen, Xiaoyan; Shah, Nilesh; Lee, Minjae; Kong, Lan; Pike, Francis; Keener, Christopher; Unruh, Mark; Finkel, Kevin; Vijayan, Anitha; Palevsky, Paul M.; Paganini, Emil; Carter, Melinda; Elder, Michele; Kellum, John A.

2014-01-01

Background Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. Methods In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. Results Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70–0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16–1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70–0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50–0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14–1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08–1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02–1.56, P < 0.03) were associated with mortality. Conclusions Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve

Role of IL-18 in atopic asthma is determined by balance of IL-18/IL-18BP/IL-18R.

PubMed

Zhang, Huiyun; Wang, Junling; Wang, Ling; Xie, Hua; Chen, Liping; He, Shaoheng

2018-01-01

It is recognized that IL-18 is related to development of asthma, but role of IL-18 in asthma remains controversial and confusing. This is largely due to lack of information on expression of IL-18 binding protein (BP) and IL-18 receptor (R) in asthma. In this study, we found that plasma levels of IL-18 and IL-18BP were elevated in asthma. The ratio between plasma concentrations of IL-18 and IL-18BP was 1:12.8 in asthma patients. We demonstrated that 13-fold more monocytes, 17.5-fold more neutrophils and 4.1-fold more B cells express IL-18BP than IL-18 in asthmatic blood, suggesting that there is excessive amount of IL-18BP to abolish actions of IL-18 in asthma. We also discovered that more IL-18R+ monocytes, neutrophils and B cells are located in asthmatic blood. Once injected, IL-18 eliminated IL-18R+ monocytes in blood, but up-regulated expression of IL-18R in lung macrophages of OVA-sensitized mice. Our data clearly indicate that the role of IL-18 in asthma is very likely to be determined by balance of IL-18/IL-18BP/IL-18R expression in inflammatory cells. Therefore, IL-18R blocking or IL-18BP activity enhancing therapies may be useful for treatment of asthma. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Lactococcus lactis carrying the pValac eukaryotic expression vector coding for IL-4 reduces chemically-induced intestinal inflammation by increasing the levels of IL-10-producing regulatory cells.

PubMed

Souza, Bianca Mendes; Preisser, Tatiane Melo; Pereira, Vanessa Bastos; Zurita-Turk, Meritxell; de Castro, Camila Prósperi; da Cunha, Vanessa Pecini; de Oliveira, Rafael Pires; Gomes-Santos, Ana Cristina; de Faria, Ana Maria Caetano; Machado, Denise Carmona Cara; Chatel, Jean-Marc; Azevedo, Vasco Ariston de Carvalho; Langella, Philippe; Miyoshi, Anderson

2016-08-30

Inflammatory bowel diseases are characterized by chronic intestinal inflammation that leads to severe destruction of the intestinal mucosa. Therefore, the understanding of their aetiology as well as the development of new medicines is an important step for the treatment of such diseases. Consequently, the development of Lactococcus lactis strains capable of delivering a eukaryotic expression vector encoding the interleukin 4 (IL-4) of Mus musculus would represent a new strategy for the elaboration of a more effective alternative therapy against Crohn's disease. The murine IL-4 ORF was cloned into the eukaryotic expression vector pValac::dts. The resulting plasmid-pValac::dts::IL-4-was transfected into CHO cells so that its functionality could be evaluated in vitro. With fluorescent confocal microscopy, flow cytometry and ELISA, it was observed that pValac::dts::IL-4-transfected cells produced IL-4, while non-transfected cells and cells transfected with the empty vector did not. Then, pValac::dts::IL-4 was inserted into L. lactis MG1363 FnBPA(+) in order to evaluate the therapeutic potential of the recombinant strain against TNBS-induced colitis. Intragastric administration of L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) was able to decrease the severity of colitis, with animals showing decreased levels of IL-12, IL-6 and MPO activity; and increased levels of IL-4 and IL-10. Finally, LP-isolated cells from mice administered TNBS were immunophenotyped so that the main IL-4 and IL-10 producers were identified. Mice administered the recombinant strain presented significantly higher percentages of F4/80(+)MHCII(+)Ly6C(-)IL-4(+), F4/80(+)MHCII(+)Ly6C(-)IL-10(+), F4/80(+)MHCII(+)Ly6C(-)CD206(+)CD124(+)IL-10(+) and CD4(+)Foxp3(+)IL10(+) cells compared to the other groups. This study shows that L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) is a good candidate to maintain the anti-inflammatory and proinflammatory balance in the gastrointestinal tract, increasing the levels

IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.

PubMed

Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P; Hackney, Jason A; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

2017-01-01

Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.

IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice

PubMed Central

Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P.; Hackney, Jason A.; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M.; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

2017-01-01

Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU. PMID:28125663

IL10 single nucleotide polymorphisms are related to upregulation of constitutive IL-10 production and susceptibility to Helicobacter pylori infection.

PubMed

Assis, Shirleide; Marques, Cintia Rodrigues; Silva, Thiago Magalhães; Costa, Ryan Santos; Alcantara-Neves, Neuza Maria; Barreto, Mauricio Lima; Barnes, Kathleen Carole; Figueiredo, Camila Alexandrina

2014-06-01

Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children. We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5' nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK. Our results shown that IL10 single nucleotide polymorphisms rs1800896 (OR = 1.63; 95% CI = 1.11-2.39), rs3024491 (OR = 1.71; 95% CI = 1.14-2.57), rs1878672 (OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 (OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori. Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti-H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer. © 2014 John Wiley & Sons Ltd.

Acronyms Gone Wild! ILL Flirts with NCIP

ERIC Educational Resources Information Center

Carlson, Al

2008-01-01

While the traditional uses of InterLibrary Loan (ILL) can be cumbersome, much of the work is now done electronically. Google and WorldCat can tell patrons which libraries in their areas owns the the titles they want, but they cannot always tell patrons whether there is a copy on the shelf available for loan. Several ILS vendors and OCLC are…

Illness perceptions and coping determine quality of life in COPD patients.

PubMed

Tiemensma, Jitske; Gaab, Erin; Voorhaar, Maarten; Asijee, Guus; Kaptein, Adrian A

2016-01-01

A key goal of chronic obstructive pulmonary disease (COPD) care is to improve patients' quality of life (QoL). For outcomes such as QoL, illness perceptions and coping are important determinants. The primary aim was to assess the associations between illness perceptions, coping and QoL in COPD patients. A secondary aim was to compare illness perceptions and coping of patients with reference values derived from the literature. A total of 100 patients were included in the study. Patients were asked to complete the Brief Illness Perception Questionnaire (B-IPQ), the Utrecht Proactive Coping Competence scale (UPCC), and a QoL item. Correlations and linear regression models were used to analyze the data. Student's t-tests were used to compare patients with COPD with reference values derived from the literature. Patients with better understanding of COPD utilized more proactive coping strategies (P=0.04). A more intense emotional response to COPD was related to less proactive coping (P=0.02). Patients who reported using more proactive coping techniques also reported to have a better QoL (P<0.01). Illness perceptions were also related to QoL: more positive illness perceptions were related to a better QoL (all P<0.05). Patients with COPD reported more negative illness perceptions than people with a common cold or patients with asthma (all P<0.01), but reported similar perceptions compared with patients with diabetes. Patients with COPD reported a moderate QoL, but appeared to be proficient in proactive coping. Illness perceptions, coping, and QoL were all associated with each other. Patients reported more strongly affected illness perceptions compared to people with a cold and patients with asthma. We postulate that a self-management intervention targeting patients' illness perceptions leads to improved QoL.

Effect of intravenous lidocaine combined with amitriptyline on pain intensity, clinical manifestations and the concentrations of IL-1, IL-6 and IL-8 in patients with fibromyalgia: A randomized double-blind study.

PubMed

Albertoni Giraldes, Ana Laura; Salomão, Reinaldo; Leal, Plinio da Cunha; Brunialti, Milena Karina Coló; Sakata, Rioko Kimiko

2016-10-01

Regarding the use of intravenous lidocaine in fibromyalgia, there are no well-controlled studies. This study aimed to evaluate the effect of intravenous lidocaine on pain intensity, clinical manifestations and plasma levels of interleukin (IL)-1, IL-6, and IL-8 in fibromyalgia patients. In a randomized double-blind study, group 1 patients received 240 mg of lidocaine in 125 mL of saline solution, while group 2 patients received 125 mL of saline, both once a week for 4 weeks (T1, T2, T3 and T4). All patients received amitriptyline. The following were assessed: pain intensity before treatment (T0) and at 1, 2, 3, 4 and 8 weeks after treatment; clinical manifestations; the fibromyalgia impact questionnaire (FIQ) before and at 4 and 8 weeks after; the levels of IL 1, 6 and 8 before and at 4 and 8 weeks after treatment. Lower pain intensity was observed in the lidocaine group at T2, with no difference at the other time points. There was a reduction in pain intensity in both groups. The use of paracetamol and tramadol and plasma levels of IL-1, IL-6 and IL-8 did not differ between the groups. Clinical manifestations and side effects did not differ between groups. The combination of 240 mg of intravenous lidocaine (once a week for 4 weeks) with 25 mg of amitriptyline for 8 weeks had no meaningful impact in fibromyalgia patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Interactive effect of calcium and gibberellin on nickel tolerance in relation to antioxidant systems in Triticum aestivum L.

PubMed

Siddiqui, Manzer H; Al-Whaibi, Mohamed H; Basalah, Mohammed O

2011-07-01

Nickel toxicity affects many metabolic facets of plants and induces anatomical and morphological changes resulting in reduced growth and productivity. To overcome the damaging effects of nickel (Ni) stress, different strategies of the application of nutrients with plant hormones are being adopted. The present experiment was carried out to assess the growth and physiological response of wheat plant (Triticum aestivum L.) cv. Samma to pre-sowing seed treatment with GA(3) alone as well as in combination with Ca(2+) and/or Ni stress. The pre-sowing seed treatment of Ni decreased all the growth characteristics (plant height, root length, fresh, and dry weight) as well as chlorophyll (Chl) content and enzyme carbonic anhydrase (CA: E.C. 4.2.1.1) activity. However, an escalation was recorded in malondialdehyde content and electrolyte leakage in plants raised from seed soaked with Ni alone. Moreover, all the growth parameters and physiological attributes (Chl content, proline (Pro) content, CA, peroxidase (E.C.1.11.1.7), catalase (E.C. 1.11.1.6), superoxide dismutase (E.C. 1.15.1.1), ascorbate peroxidase (E.C. 1.11.1.11), and glutathione reductase (E.C. 1.6.4.2) were enhanced in the plants developed from the seeds soaked with the combination of GA(3) (10(-6) M), Ca(2+), and Ni. The present study showed that pre-sowing seed treatment of GA(3) with Ca(2+) was more capable in mitigation of adverse effect of Ni toxicity by improving the antioxidant system and Pro accumulation.

[Gene IL6 G(-174)C and gene IL10 G(-1082)A polymorphisms are associated with unfavourable outcomes in patients with acute coronary syndrome].

PubMed

Blagodatskikh, K A; Evdokimova, M A; Agapkina, Iu V; Nikitin, A G; Brovkin, A N; Pushkov, A A; Blagodatskikh, E G; Kudriasheva, O Iu; Osmolovskaia, V S; Minushkina, L O; Kochkina, M S; Selezneva, N D; Dankovtseva, E N; Chumakova, O S; Baklanova, T N; Talyzin, P A; Reznichenko, N E; Donetskaia, O P; Tereshchenko, S N; Krasil'nikova, E S; Dzhaiani, N A; Akatova, E V; Glezer, M G; Galiavich, A S; Zakirova, V B; Kaziolova, N A; Timofeeva, I V; Iagoda, A V; Boeva, O I; Katel'nitskaia, L I; Khorolets, E V; Shlyk, S V; Volkova, É G; Margarian, M P; Guz', O I; Konstantinov, V O; Timofeeva, N V; Sidorenko, B A; Zateĭshchikov, D A; Nosikov, V V

2010-01-01

We investigated the association of gene IL6 G(-174)C polymorphism and gene IL10 G(-1082)A polymorphism with coronary artery disease (CAD) in the Russian population. A total of 1145 patients with CAD diagnose on the basis of clinical studies in cardiological hospitals of Moscow, St -Petersburg, Kazan, Chelyabinsk, Perm, Stavropol and Rostov-on-Don. Supervision term was 9.10 +/- 5.03 months (the maximum term 18 months). In case of gene IL10 G(-1082)A polymorphism we determined that patients with CAD diagnose and A alleles gene IL10 had unfavorable outcome more often than patients with homozygous G alleles. Survival time from end point from carrier genotype GA and AA is 11.68 +/- 0.67 months against 12.69 +/- 0.65 months from carrier phenotype GG gene IL10 (chi2 = 4.13, p = 0.042). The group studied do not differ significantly with respect to the distributions of gene IL6 G(-174)C alleles and genotypes. However in case combined group studies of gene IL10 G(-1082)A polymorphism and IL6 G(-174)C polymorphism we determined that patients with CAD diagnose and carrier genotype GG gene IL6 and genotype GA and AA gene IL10 had unfavorable outcome more often (survival time 11.01 +/- 1.24 months) than patients with genotype CC and CG gene IL6 and genotype GG gene IL10 (survival time 13.28 +/- 0.83 months) chi2 = 10.23, p = 0.017. The obtained data allows assuming the important role of the IL6 and IL10 genes which are responsible for functioning of inflammation system, in the accelerated formation of failures at the patients who had a coronary syndrome.

Recovery of zinc and cadmium from spent batteries using Cyphos IL 102 via solvent extraction route and synthesis of Zn and Cd oxide nanoparticles.

PubMed

Singh, Rashmi; Mahandra, Harshit; Gupta, Bina

2017-09-01

The overall aim of this study is to separate and recover zinc and cadmium from spent batteries. For this purpose Cyphos IL 102 diluted in toluene was employed for the extraction and recovery of Zn and Cd from Zn-C and Ni-Cd batteries leach liquor. The influence of extractant concentration for the leach liquors of Zn-C (0.01-0.05mol/L) and Ni-Cd (0.04-0.20mol/L) batteries has been investigated. Composition of the leach liquor obtained from Zn-C/Ni-Cd spent batteries is Zn - 2.18g/L, Mn - 4.59g/L, Fe - 4.0×10 -3 g/L, Ni - 0.2×10 -3 g/L/Cd - 4.28g/L, Ni - 0.896×10 -1 g/L, Fe - 0.148g/L, Co - 3.77×10 -3 g/L, respectively. Two stage counter current extraction at A/O 1:1 and 3:2 with 0.04mol/L and 0.2mol/L Cyphos IL 102 for Zn and Cd, respectively provide more than 99.0% extraction of both the metal ions with almost negligible extraction of associated metal ions. A stripping efficiency of around 99.0% for Zn and Cd was obtained at O/A 1:1 using 1.0mol/L HNO 3 in two and three counter current stages, respectively. ZnO and CdO were also synthesized using the loaded organic phase and characterized using XRD, FE-SEM and EDX techniques. XRD peaks of ZnO and CdO correspond to zincite and monteponite, respectively. The average particle size was ∼27.0nm and ∼37.0nm for ZnO and CdO, respectively. The EDX analysis of ZnO and CdO shows almost 1:1 atomic percentage. Copyright © 2017. Published by Elsevier Ltd.

[Changes of CD(4)(+) Foxp3+ regulatory T cells and CD(4)(+)IL-17+T cells in acrolein exposure rats].

PubMed

Wei, Ming; Tu, Ling; Liang, Yinghong; Li, Jia; Gong, Yanjie; Zhang, Yihua; Yang, Lu

2015-09-01

To evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats. Forty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. Levels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 ± 1.89) ng/L, (76.73 ± 5.57) ng/L], and BALF [(79.07 ± 5.67) ng/L, (96.61 ± 6.44) ng/L] compared with the 2 wk control group [(40.05 ± 3.12) ng/L, (56.75 ± 4.37) ng/L] and the 4 wk control group [(38.75 ± 3.23) ng/L, (53.27 ± 4.48) ng/L], all P<0.01. IL-6 was increased in the 2 wk and the 4 wk acrolein exposure group [ (33.28 ± 2.27) ng/L, (46.24 ± 3.16) ng/L] compared with the 2 wk and the 4 wk control group [ (16.37 ± 1.49) ng/L, (17.02 ± 1.43) ng/L] in BALF.Ratio of Th17 was higher in the 2 wk and the 4 wk acrolein exposure groups in peripheral blood (1.82 ± 0.18) %, (3.75 ± 0.48) % and BALF [(7.23 ± 0.27) %, (8.12 ± 0.38) %] compared with the 2 wk [(0.96 ± 0.07) %, (5.64 ± 0.63) %] and the 4 wk control group [(1.01 ± 0.08) %, (5.86 ± 0.57) %]. Ratio of Treg in BALF was higher in the acrolein exposure groups [ (8.83 ± 0.52) %, (12.05 ± 0.74) %] compared

The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis.

PubMed

Eliav, Eli; Benoliel, Rafael; Herzberg, Uri; Kalladka, Mythili; Tal, Michael

2009-05-01

Inflammation along a nerve trunk (perineural inflammation), without detectable axonal damage, has been shown to induce transient pain in the organ supplied by the nerve. The aims of the present study were to study the role IL-6 and IL-1beta, in pain induced by perineural inflammation. IL-6 and IL-1beta secretion from rat's sciatic nerves, L-5 Dorsal Root Ganglia (DRG), and the hind paw skin, 3 and 8 days following exposure of the nerve to Complete Freund's Adjuvant (CFA), were measured using ELISA method. Hind paw tactile-allodynia, mechano-hyperalgesia, heat-allodynia and electrical detection thresholds were tested up to 8 days following the application of CFA, IL-6 or IL-1beta adjacent to the sciatic nerve trunk. Employing electrophysiological recording, saphenous nerve spontaneous activity, nerve trunk mechano-sensitivity and paw tactile detection threshold (determined by recording action potential induced by the lowest mechanical stimulus) were assessed 3 and 8 days following exposure of the nerve trunk to CFA, IL-6, or IL-1beta. IL-6 and IL-1beta secretion from the nerve was significantly elevated on the 3rd day post-operation (DPO). On the 8th DPO, IL-6 levels returned to baseline while IL-1beta levels remained significantly elevated. The DRG cytokine's level was increased on the 3rd and 8th DPOs, contralateral cytokine's level was increased on the 3rd DPO. The skin IL-6 level was increased bilaterally on the 3rd DPO and returned to baseline on the 8th DPO. IL-1beta levels increased in the affected side on the 3rd and bilaterally on the 8th DPO. Direct application of IL-6 or CFA on the sciatic nerve induced significant hind paw tactile-allodynia from the 1st to 5th DPOs, reduced electrical detection threshold from the 1st to 3rd DPOs, mechano-hyperalgesia from 3rd to 5th DPOs and heat-allodynia on the 3rd DPO. Direct application of IL-1beta induced paw tactile and heat-allodynia on the 7-8th DPOs and mechano-hyperalgesia on the 5-8th DPOs. Perineural

Concepts of illness in Icelandic children.

PubMed

Hansdottir, I; Malcarne, V L

1998-06-01

To investigate the development of illness concepts among healthy Icelandic children. Participants were 68 schoolchildren, 6-7, 10-11, and 14-15 years of age, and their parents. Cognitive developmental level and understanding of physical illness were assessed within a Piagetian framework. In addition, illness experience and illness behaviors (Child Illness Behavior Questionnaire) were assessed. Results were consistent with previous studies in that the development of illness concepts among Icelandic children was consistent with Piaget's theory of cognitive development. No relation was found between illness experience and understanding of illness. A more mature understanding of illness was related to willingness to report the onset of illness. The results suggest that findings from previous studies may be generalized to a broader population.

IL-6 does not predict current urolithiasis in stone formers.

PubMed

Rieder, Jocelyn M; Nisbet, Alan A; Lesser, Timothy; Franke, Ethan I; Brusky, John P; Parekh, Ashish R; Kaptein, John; Bellman, Gary C

2008-10-01

Interleukin-6 (IL-6), an inflammatory marker, has previously been found to be elevated in the urine of patients with urolithiasis. Oxalate and other stone precursors have been shown to increase IL-6 production in proximal tubular epithelial cells in vitro. We examined whether urinary IL-6 could be used as a screening test to determine current urolithiasis in individuals who are known to form urinary stones. Thirty-five adult patients with current urolithiasis demonstrated on imaging were enrolled in the study. Exclusion criteria included disease known to elevate IL-6. Each patient provided a pre-treatment urine specimen and one month after proven to be stone-free an additional urine specimen was obtained. The urinary IL-6/creatinine ratio was determined for both specimens and compared. Ten patients provided both specimens. The mean pre-operative urinary IL-6/creatinine ratio before the procedure was 1.63 pg/mL. The mean post procedure urinary IL-6/creatinine ratio after the patient was confirmed to be stone-free was 1.81 pg/mL. These were not significantly different (p=0.38). Preoperative urinary IL-6/creatinine ratio did not correlate to stone size (r=0.15) and no correlation was seen between time from treatment and stone free IL-6/creatinine ratio (r=0.48). Urinary IL-6 is not a good screening test for current urolithiasis in stone-forming individuals. It is elevated whether the stone is present or not.

A lentiviral vaccine expressing KMP11-HASPB fusion protein increases immune response to Leishmania major in BALB/C.

PubMed

Mortazavidehkordi, Nahid; Fallah, Ali; Abdollahi, Abbas; Kia, Vahid; Khanahmad, Hossein; Najafabadi, Zahra Ghayour; Hashemi, Nooshin; Estiri, Bahareh; Roudbari, Zahra; Najafi, Ali; Farjadfar, Akbar; Hejazi, Seyed Hossein

2018-05-29

Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania-specific protein that antibodies are produced against it in the sera of Leishmania-infected individuals. Kinetoplastid membrane protein 11 (KMP11) is another Leishmania antigen and considered as the suitable candidate for vaccine development Leishmaniasis. It is a highly conserved surface protein expressed in both promastigotes and amastigotes. In this study, KMP11 and HASPB coding sequences were cloned into a pCDH-cGFP lentiviral vector as a fusion protein to be used as a DNA vaccine against L. major. The KMP11-HASPB fusion protein was successfully expressed as evidenced by RT-PCR and Western blot assays. The effect of the vaccine was determined by evaluating the level of IFN-γ, IL-10, IgG1, and IgG2a performed using ELISA as well as determining the parasite load after challenge with L. major in vaccinated mice. The results revealed that IFN-γ, IL-10, IgG1, and IgG2a significantly increased after vaccination using KMP11-HASPB-expressing lentiviruses in BALB/c mice. It is noteworthy that the level of IFN-γ and IgG2a was higher than that of IL-10 and IgG1, respectively, which indicates the activation Th1 cells, macrophages, and cellular immunity. Moreover, the parasite load in the spleen and lymph node of vaccinated mice after challenge was significantly lower than that of controls.

Interleukin 1 Receptor (IL-1R1) Activation Exacerbates Toxin-Induced Acute Kidney Injury.

PubMed

Privratsky, Jamie R; Zhang, Jiandong; Lu, Xiaohan; Rudemiller, Nathan; Wei, Qingqing; Yu, Yen-Rei; Gunn, Michael Dee; Crowley, Steven D

2018-05-23

Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Cisplatin is an effective chemotherapeutic agent whose administration is limited by nephrotoxicity. Therapies to prevent cisplatin-induced AKI are lacking. While tumor necrosis factor-α (TNF) plays a key role in the pathogenesis of cisplatin nephrotoxicity, the immune signaling pathways that trigger TNF generation in this context require elucidation. Sterile injury triggers the release and activation of both isoforms of interleukin(IL)-1, IL-1α and IL-1β, and stimulation of the interleukin-1 receptor (IL-1R1) by these ligands engages a pro-inflammatory signaling cascade that induces TNF induction. We therefore hypothesized that IL-1R1 activation exacerbates cisplatin-induced AKI by inducing TNF production thereby augmenting inflammatory signals between kidney parenchymal cells and infiltrating myeloid cells. IL-1R1+/+ (WT) and IL-1R1-/- (KO) mice were subjected to cisplatin-induced AKI. Compared to WT mice, IL-1R1 KO mice had attenuated AKI as measured by serum creatinine and BUN; renal NGAL mRNA levels; and blinded histological analysis of kidney pathology. In the cisplatin-injured kidney, IL-1R1 KO mice had diminished levels of whole kidney TNF and fewer Ly6G-expressing neutrophils. In addition, an unbiased machine learning analysis of intra-renal immune cells revealed a diminished number of CD11bint/CD11cint myeloid cells in IL-1R1 KO injured kidneys compared to IL-1R1 WT kidneys. Following cisplatin, IL-1R1 KO kidneys, compared to WTs, had fewer TNF-producing macrophages, CD11bint/CD11cint cells, and neutrophils, consistent with an effect of IL-1R1 to polarize intra-renal myeloid cells toward a pro-inflammatory phenotype. Interruption of IL-1-dependent signaling pathways warrants further evaluation to decrease nephrotoxicity during cisplatin therapy.

Do healthy school meals affect illness, allergies and school attendance in 8- to 11-year-old children? A cluster-randomised controlled study.

PubMed

Laursen, R P; Lauritzen, L; Ritz, C; Dyssegaard, C B; Astrup, A; Michaelsen, K F; Damsgaard, C T

2015-05-01

A nutritionally adequate diet in childhood is important for health and resistance of allergies and infections. This study explored the effects of school meals rich in fish, vegetables and fibre on school attendance, asthma, allergies and illness in 797 Danish 8- to 11-year-old children. No comparable studies conducted in high-income settings have been identified. The OPUS School Meal Study was a cluster-randomised cross-over trial. Children from third and fourth grades at nine Danish schools received school meals or usual packed lunch (control) for two 3-month periods. Occurrence and duration of illnesses, asthma and allergies during the last 14 days were recorded by parental questionnaires at baseline and after each 3-month period. Self-reported well-being was assessed by visual analogue scales. The school meals did not affect school attendance, parent-reported occurrence or duration of asthma and allergies or self-reported well-being. The most common symptoms of illness were stomach pain (24%), headache (28%) and cold (24%). A slightly higher number of children experienced headaches in the school meal (27%) compared with the control period (22%) (P=0.02). However, subgroup analyses showed that this effect was only seen in children eating school meals in the classroom (P=0.007), and not in common dining areas (P=0.2). No effect was found on other symptoms of illness. Provision of nutritionally balanced school meals did not affect school attendance, asthma, allergies, illness or well-being in 8- to 11-year-old children. The slight increase in occurrence of headaches seems to be related to the physical eating environment.

Interleukin-11 binds specific EF-hand proteins via their conserved structural motifs.

PubMed

Kazakov, Alexei S; Sokolov, Andrei S; Vologzhannikova, Alisa A; Permyakova, Maria E; Khorn, Polina A; Ismailov, Ramis G; Denessiouk, Konstantin A; Denesyuk, Alexander I; Rastrygina, Victoria A; Baksheeva, Viktoriia E; Zernii, Evgeni Yu; Zinchenko, Dmitry V; Glazatov, Vladimir V; Uversky, Vladimir N; Mirzabekov, Tajib A; Permyakov, Eugene A; Permyakov, Sergei E

2017-01-01

Interleukin-11 (IL-11) is a hematopoietic cytokine engaged in numerous biological processes and validated as a target for treatment of various cancers. IL-11 contains intrinsically disordered regions that might recognize multiple targets. Recently we found that aside from IL-11RA and gp130 receptors, IL-11 interacts with calcium sensor protein S100P. Strict calcium dependence of this interaction suggests a possibility of IL-11 interaction with other calcium sensor proteins. Here we probed specificity of IL-11 to calcium-binding proteins of various types: calcium sensors of the EF-hand family (calmodulin, S100B and neuronal calcium sensors: recoverin, NCS-1, GCAP-1, GCAP-2), calcium buffers of the EF-hand family (S100G, oncomodulin), and a non-EF-hand calcium buffer (α-lactalbumin). A specific subset of the calcium sensor proteins (calmodulin, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants of 1-19 μM. These proteins share several amino acid residues belonging to conservative structural motifs of the EF-hand proteins, 'black' and 'gray' clusters. Replacements of the respective S100P residues by alanine drastically decrease its affinity to IL-11, suggesting their involvement into the association process. Secondary structure and accessibility of the hinge region of the EF-hand proteins studied are predicted to control specificity and selectivity of their binding to IL-11. The IL-11 interaction with the EF-hand proteins is expected to occur under numerous pathological conditions, accompanied by disintegration of plasma membrane and efflux of cellular components into the extracellular milieu.

miR-206 Inhibits Stemness and Metastasis of Breast Cancer by Targeting MKL1/IL11 Pathway.

PubMed

Samaeekia, Ravand; Adorno-Cruz, Valery; Bockhorn, Jessica; Chang, Ya-Fang; Huang, Simo; Prat, Aleix; Ha, Nahun; Kibria, Golam; Huo, Dezheng; Zheng, Hui; Dalton, Rachel; Wang, Yuhao; Moskalenko, Grigoriy Y; Liu, Huiping

2017-02-15

Purpose: Effective targeting of cancer stem cells is necessary and important for eradicating cancer and reducing metastasis-related mortality. Understanding of cancer stemness-related signaling pathways at the molecular level will help control cancer and stop metastasis in the clinic. Experimental Design: By analyzing miRNA profiles and functions in cancer development, we aimed to identify regulators of breast tumor stemness and metastasis in human xenograft models in vivo and examined their effects on self-renewal and invasion of breast cancer cells in vitro To discover the direct targets and essential signaling pathways responsible for miRNA functions in breast cancer progression, we performed microarray analysis and target gene prediction in combination with functional studies on candidate genes (overexpression rescues and pheno-copying knockdowns). Results: In this study, we report that hsa-miR-206 suppresses breast tumor stemness and metastasis by inhibiting both self-renewal and invasion. We identified that among the candidate targets, twinfilin ( TWF1 ) rescues the miR-206 phenotype in invasion by enhancing the actin cytoskeleton dynamics and the activity of the mesenchymal lineage transcription factors, megakaryoblastic leukemia (translocation) 1 (MKL1), and serum response factor (SRF). MKL1 and SRF were further demonstrated to promote the expression of IL11 , which is essential for miR-206's function in inhibiting both invasion and stemness of breast cancer. Conclusions: The identification of the miR-206/TWF1/MKL1-SRF/IL11 signaling pathway sheds lights on the understanding of breast cancer initiation and progression, unveils new therapeutic targets, and facilitates innovative drug development to control cancer and block metastasis. Clin Cancer Res; 23(4); 1091-103. ©2016 AACR . ©2016 American Association for Cancer Research.

Pinostrobin and Cajanus lactone isolated from Cajanus cajan (L.) leaves inhibits TNF-α and IL-1β production: in vitro and in vivo experimentation.

PubMed

Patel, Neeraj K; Bhutani, Kamlesh K

2014-06-15

The tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) inhibitory activities of Cajanus cajan (leaves) crude methanolic extract, its fractions and its phytochemical constituents were evaluated in lipopolysaccharide (LPS) stimulated RAW 264.7 and J774A.1 cells. Phytochemical investigation of the active ethyl acetate (CCE) and n-butanol (CCB) fractions of C. cajan L. leaves yielded 14 compounds. It was observed that both pinostrobin (9) and cajanus lactone (4) were found to be most active in inhibiting TNF-α (IC50<22 μM) and IL-1β (IC50<40 μM) whereas compounds 2, 3, 5-8, 10 and 14 showed moderate and mild effects (IC50=35.50-81.22 μM for TNF-α and 38.23-89.10 μM for IL-1β) in both the cell lines. Furthermore, at dose of 20mg/kg, both pinostrobin (9) and cajanus lactone (4) were found to reduce LPS-induced TNF-α levels by 48.6% and 55.0% respectively and IL-1β levels by 53.1% and 41.8% respectively in Sprague Dawley (SD) rats. These findings suggest that C. cajan L. leaves can be developed as an effective herbal remedy for the treatment and prevention of inflammation or associated ailments. Copyright © 2014 Elsevier GmbH. All rights reserved.

Evaluation of IL-12RB1, IL-12B, CXCR-3 and IL-17a expression in cases affected by a non-healing form of cutaneous leishmaniasis: an observational study design

PubMed Central

Moafi, Mohammad; Rezvan, Hossein; Sherkat, Roya; Taleban, Roya; Asilian, Ali; Zarkesh Esfahani, Seyed Hamid; Nilforoushzadeh, Mohammad Ali; Jaffary, Fariba; Feizi, Awat

2017-01-01

Introduction Seldom cutaneous leishmaniasis (CL) may present as a lasting and active lesion(s), known as a non-healing form of CL (NHCL). Non-functional type 1 T helper (Th1) cells are assumed the most important factor in the outcome of the disease. The present study aims to assess some molecular defects that potentially contribute to Th1 impairment in NHCL. Methods and analysis This prospective observational study will be implemented among five groups. The first and second groups comprise patients afflicted with non-healing and healing forms of CL, respectively. The third group consists of those recovered participants who have scars as a result of CL. Those participants who have never lived or travelled to endemic areas of leishmaniasis will comprise the fourth group. The fifth group comprises participants living in hyperendemic areas for leishmaniasis, although none of them have been afflicted by CL. The aim is to recruit 10 NHCL cases and 30 participants in each of the other groups. A leishmanin skin test (LST) will be performed to assess in vivo immunity against the Leishmania infection. The cytokine profile (interleukin (IL)-12p70, interferon (IFN)-γ, C-X-C motif chemokine ligand (CXCL)-11 and IL-17a) of the isolated peripheral blood mononuclear cells (PBMCs) will be evaluated through ELISA. Real-time PCR will determine the C-X-C motif chemokine receptor (CXCR)-3 and IL-17a gene expression and expression of IL-12Rβ1 will be assessed by flow cytometry. Furthermore, IL-12B and IL-12RB1 mutation analysis will be performed. Discussion It is anticipated that the outcome of the current study will identify IL-12B and IL-12RB1 mutations, which lead to persistent lesions of CL. Furthermore, our expected results will reveal an association between NHCL and pro-inflammatory cytokines (IL-12p70, IFN-γ IL-17a and CXCL-11), as well as CXCR-3 expression. Ethics and dissemination This study has been approved by a local ethical committee. The final results will be

Evaluation of IL-12RB1, IL-12B, CXCR-3 and IL-17a expression in cases affected by a non-healing form of cutaneous leishmaniasis: an observational study design.

PubMed

Moafi, Mohammad; Rezvan, Hossein; Sherkat, Roya; Taleban, Roya; Asilian, Ali; Zarkesh Esfahani, Seyed Hamid; Nilforoushzadeh, Mohammad Ali; Jaffary, Fariba; Feizi, Awat

2017-01-27

Seldom cutaneous leishmaniasis (CL) may present as a lasting and active lesion(s), known as a non-healing form of CL (NHCL). Non-functional type 1 T helper (Th1) cells are assumed the most important factor in the outcome of the disease. The present study aims to assess some molecular defects that potentially contribute to Th1 impairment in NHCL. This prospective observational study will be implemented among five groups. The first and second groups comprise patients afflicted with non-healing and healing forms of CL, respectively. The third group consists of those recovered participants who have scars as a result of CL. Those participants who have never lived or travelled to endemic areas of leishmaniasis will comprise the fourth group. The fifth group comprises participants living in hyperendemic areas for leishmaniasis, although none of them have been afflicted by CL. The aim is to recruit 10 NHCL cases and 30 participants in each of the other groups. A leishmanin skin test (LST) will be performed to assess in vivo immunity against the Leishmania infection. The cytokine profile (interleukin (IL)-12p70, interferon (IFN)-γ, C-X-C motif chemokine ligand (CXCL)-11 and IL-17a) of the isolated peripheral blood mononuclear cells (PBMCs) will be evaluated through ELISA. Real-time PCR will determine the C-X-C motif chemokine receptor (CXCR)-3 and IL-17a gene expression and expression of IL-12Rβ1 will be assessed by flow cytometry. Furthermore, IL-12B and IL-12RB1 mutation analysis will be performed. It is anticipated that the outcome of the current study will identify IL-12B and IL-12RB1 mutations, which lead to persistent lesions of CL. Furthermore, our expected results will reveal an association between NHCL and pro-inflammatory cytokines (IL-12p70, IFN-γ IL-17a and CXCL-11), as well as CXCR-3 expression. This study has been approved by a local ethical committee. The final results will be disseminated through peer-reviewed journals and scientific conferences

IL233, A Novel IL-2 and IL-33 Hybrid Cytokine, Ameliorates Renal Injury.

PubMed

Stremska, Marta E; Jose, Sheethal; Sabapathy, Vikram; Huang, Liping; Bajwa, Amandeep; Kinsey, Gilbert R; Sharma, Poonam R; Mohammad, Saleh; Rosin, Diane L; Okusa, Mark D; Sharma, Rahul

2017-09-01

CD4 + Foxp3 + regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4 + T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone. Accordingly, we generated a novel hybrid cytokine (IL233) bearing the activities of IL-2 and IL-33 for efficient targeting to Tregs. IL233 treatment increased the number of Tregs in blood and spleen and prevented IRI more efficiently than a mixture of IL-2 and IL-33. Injection of IL233 also increased the numbers of Tregs in renal compartments. Moreover, IL233-treated mice had fewer splenic Tregs and more Tregs in kidneys after IRI. In vitro , splenic Tregs from IL233-treated mice suppressed CD4 + T cell proliferation better than Tregs from saline-treated controls. IL233 treatment also improved the ability of isolated Tregs to inhibit IRI in adoptive transfer experiments and protected mice from cisplatin- and doxorubicin-induced nephrotoxic injury. Finally, treatment with IL233 increased the proportion of ST2-bearing innate lymphoid cells (ILC2) in blood and kidneys, and adoptive transfer of ILC2 also protected mice from IRI. Thus, the novel IL233 hybrid cytokine, which utilizes the cooperation of IL-2 and IL-33 to enhance Treg- and ILC2-mediated protection from AKI, bears strong therapeutic potential. Copyright © 2017 by the American Society of Nephrology.

In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.

PubMed

Garcia-Ruíz, G; Flores-Espinosa, P; Preciado-Martínez, E; Bermejo-Martínez, L; Espejel-Nuñez, A; Estrada-Gutierrez, G; Maida-Claros, R; Flores-Pliego, A; Zaga-Clavellina, Veronica

2015-10-07

During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers. Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P < 0.05 was considered statistically significant. In comparison to the explants incubated with vehicle, the LPS treatment led to a significant increase in the level of all cytokines. In comparison to the explants treated only with LPS, pre-treatment with 0.01-1.0 μM progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone. The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.

Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2–dependent adult T-cell leukemia

PubMed Central

Zhang, Meili; Mathews Griner, Lesley A.; Ju, Wei; Duveau, Damien Y.; Guha, Rajarshi; Petrus, Michael N.; Wen, Bernard; Maeda, Michiyuki; Shinn, Paul; Ferrer, Marc; Conlon, Kevin D.; Bamford, Richard N.; O’Shea, John J.; Thomas, Craig J.; Waldmann, Thomas A.

2015-01-01

Adult T-cell leukemia (ATL) develops in individuals infected with human T-cell lymphotropic virus-1 (HTLV-1). Presently there is no curative therapy for ATL. HTLV-1–encoded protein Tax (transactivator from the X-gene region) up-regulates Bcl-xL (B-cell lymphoma-extra large) expression and activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems, resulting in amplified JAK/STAT signaling. Inhibition of JAK signaling reduces cytokine-dependent ex vivo proliferation of peripheral blood mononuclear cells (PBMCs) from ATL patients in smoldering/chronic stages. Currently, two JAK inhibitors are approved for human use. In this study, we examined activity of multiple JAK inhibitors in ATL cell lines. The selective JAK inhibitor ruxolitinib was examined in a high-throughput matrix screen combined with >450 potential therapeutic agents, and Bcl-2/Bcl-xL inhibitor navitoclax was identified as a strong candidate for multicomponent therapy. The combination was noted to strongly activate BAX (Bcl-2-associated X protein), effect mitochondrial depolarization, and increase caspase 3/7 activities that lead to cleavage of PARP (poly ADP ribose polymerase) and Mcl-1 (myeloid cell leukemia 1). Ruxolitinib and navitoclax independently demonstrated modest antitumor efficacy, whereas the combination dramatically lowered tumor burden and prolonged survival in an ATL murine model. This combination strongly blocked ex vivo proliferation of five ATL patients’ PBMCs. These studies provide support for a therapeutic trial in patients with smoldering/chronic ATL using a drug combination that inhibits JAK signaling and antiapoptotic protein Bcl-xL. PMID:26396258

Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

PubMed

Halwani, Rabih; Sultana, Asma; Vazquez-Tello, Alejandro; Jamhawi, Amer; Al-Masri, Abeer A; Al-Muhsen, Saleh

2017-11-01

In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

Investigation of Behaviorally Modified Rats for Use in Explosives Detection Systems

DTIC Science & Technology

1981-12-01

c. 4o t W iet s mi4w dltr’elm-jueiealolf- ltii*liti . .t.wnu sit - ass e-nz Iati ifovit l iutr in jIrrf-rt-F1wr to. thr lkillin aitinal. il if" O.W.tf...8217joizzle iwo%𔃾 ill .,rdtr . d1a44, tit" alsa Ilsr"’I (olf..~ .4144 if i Ow .1fi4j4.Iiumi.4-l4p sit Iii- t.’ l m~I14r.414r1 d4 atiim l-. leo *.rt1.-r is...urvisisi-. I Ifi- -1its 1%a- 1.11, -esi f, rf a 1 -Illijvvt. li-es ill [ies 1 irtlit- wyit eirmr ilist-- sit . ii- IsrpIllssLitinitijl 1Imi-iid

Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes.

PubMed

Kotenko, S V; Izotova, L S; Mirochnitchenko, O V; Esterova, E; Dickensheets, H; Donnelly, R P; Pestka, S

2001-01-26

Interleukin-10 (IL-10)-related T cell-derived inducible factor (IL-TIF; provisionally designated IL-22) is a cytokine with limited homology to IL-10. We report here the identification of a functional IL-TIF receptor complex that consists of two receptor chains, the orphan CRF2-9 and IL-10R2, the second chain of the IL-10 receptor complex. Expression of the CRF2-9 chain in monkey COS cells renders them sensitive to IL-TIF. However, in hamster cells both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functional IL-TIF receptor complex. The CRF2-9 chain (or the IL-TIF-R1 chain) is responsible for Stat recruitment. Substitution of the CRF2-9 intracellular domain with the IFN-gammaR1 intracellular domain changes the pattern of IL-TIF-induced Stat activation. The CRF2-9 gene is expressed in normal liver and kidney, suggesting a possible role for IL-TIF in regulating gene expression in these tissues. Each chain, CRF2-9 and IL-10R2, is capable of binding IL-TIF independently and can be cross-linked to the radiolabeled IL-TIF. However, binding of IL-TIF to the receptor complex is greater than binding to either receptor chain alone. Sharing of the common IL-10R2 chain between the IL-10 and IL-TIF receptor complexes is the first such case for receptor complexes with chains belonging to the class II cytokine receptor family, establishing a novel paradigm for IL-10-related ligands similar to the shared use of the gamma common chain (gamma(c)) by several cytokines, including IL-2, IL-4, IL-7, IL-9, and IL-15.

Serial urinary IL-2, IL-6, IL-8, TNFalpha, UBC, CYFRA 21-1 and NMP22 during follow-up of patients with bladder cancer receiving intravesical BCG.

PubMed

Sanchez-Carbayo, M; Urrutia, M; Romani, R; Herrero, M; Gonzalez de Buitrago, J M; Navajo, J A

2001-01-01

We evaluated the potential role of serial preinstillation levels of several interleukins, TNFalpha and urinary tumor markers to monitor patients with bladder cancer receiving intravesical BCG. 121 urine samples were collected from: patients with bladder cancer treated with BCG (group 1); patients with bladder cancer receiving other intravesical treatment (group 2) and patients with urinary tract infections (group 3). Cytokines [IL-2, IL6 and [L8] and TNFalpha and urinary tumor markers [UBC, CYFRA 21-1 and NMP22] were measured by immunoassays. In 3 out of 15 BCG non-responders that recurred over the period of the study, no cytokine peak for IL-2, IL-6 or TNFa were detected. Urinary tumor markers increased in 2 out of 3 of these patients earlier than scheduled cystoscopies. Cytokine measurement was heterogeneous among 12 out of 15 BCG-responding patients: there were low levels of IL-6 and TNFalpha and peaks of IL-2 and IL-8 in 10 out of 12 and 4 out of 12 patients, respectively. During responding patients' follow-up we observed false-positive results in 7 out of 65 urine samples for UBC, 8 out of 65 for CYFRA 21-1 and 20 out of 65 for NMP22. Urinary tract infections were the main factor associated with non-specific elevations of IL-6 and IL-8 and urinary tumor markers in all groups of patients. Although larger series are required to confirn our preliminary observations, our data argue for a potential predictive role for IL-2 of favourable response to BCG therapy. Monitoring BCG with urinary tumor markers could early detect recurrence in non-responding patients.

L-histidine inhibits biofilm formation and FLO11-associated phenotypes in Saccharomyces cerevisiae flor yeasts.

PubMed

Bou Zeidan, Marc; Zara, Giacomo; Viti, Carlo; Decorosi, Francesca; Mannazzu, Ilaria; Budroni, Marilena; Giovannetti, Luciana; Zara, Severino

2014-01-01

Flor yeasts of Saccharomyces cerevisiae have an innate diversity of Flo11p which codes for a highly hydrophobic and anionic cell-wall glycoprotein with a fundamental role in biofilm formation. In this study, 380 nitrogen compounds were administered to three S. cerevisiae flor strains handling Flo11p alleles with different expression levels. S. cerevisiae strain S288c was used as the reference strain as it cannot produce Flo11p. The flor strains generally metabolized amino acids and dipeptides as the sole nitrogen source, although with some exceptions regarding L-histidine and histidine containing dipeptides. L-histidine completely inhibited growth and its effect on viability was inversely related to Flo11p expression. Accordingly, L-histidine did not affect the viability of the Δflo11 and S288c strains. Also, L-histidine dramatically decreased air-liquid biofilm formation and adhesion to polystyrene of the flor yeasts with no effect on the transcription level of the Flo11p gene. Moreover, L-histidine modified the chitin and glycans content on the cell-wall of flor yeasts. These findings reveal a novel biological activity of L-histidine in controlling the multicellular behavior of yeasts [corrected].

L-Histidine Inhibits Biofilm Formation and FLO11-Associated Phenotypes in Saccharomyces cerevisiae Flor Yeasts

PubMed Central

Bou Zeidan, Marc; Zara, Giacomo; Viti, Carlo; Decorosi, Francesca; Mannazzu, Ilaria; Budroni, Marilena; Giovannetti, Luciana; Zara, Severino

2014-01-01

Flor yeasts of Saccharomyces cerevisiae have an innate diversity of FLO11 which codes for a highly hydrophobic and anionic cell-wall glycoprotein with a fundamental role in biofilm formation. In this study, 380 nitrogen compounds were administered to three S. cerevisiae flor strains handling FLO11 alleles with different expression levels. S. cerevisiae strain S288c was used as the reference strain as it cannot produce FLO11p. The flor strains generally metabolized amino acids and dipeptides as the sole nitrogen source, although with some exceptions regarding L-histidine and histidine containing dipeptides. L-histidine completely inhibited growth and its effect on viability was inversely related to FLO11 expression. Accordingly, L-histidine did not affect the viability of the Δflo11 and S288c strains. Also, L-histidine dramatically decreased air–liquid biofilm formation and adhesion to polystyrene of the flor yeasts with no effect on the transcription level of the FLO11 gene. Moreover, L-histidine modified the chitin and glycans content on the cell-wall of flor yeasts. These findings reveal a novel biological activity of L-histidine in controlling the multicellular behavior of yeasts. PMID:25369456

Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes.

PubMed

Yadlapati, Sujani; Efthimiou, Petros

2016-01-01

Cryopyrin-associated periodic syndromes (CAPS) is a rare group of autoinflammatory disorders that includes familial cold autoinflammatory syndrome or FCAS, Muckle-wells syndrome or MWS, and neonatal-onset multisystem inflammatory disease or NOMID. CAPS is caused by a mutation in the NOD-like receptor family, pyrin domain containing 3 (NLRP3) gene. This ultimately leads to increased production of interleukin (IL)-1β. IL-1β is a biologically active member of the IL-1 family. It is not only a pro-inflammatory cytokine responsible for features such as fever, rash, and arthritis, but is also a major mediator in the central pathways of fatigue. Fatigue is a major component of CAPS and is associated with severely compromised quality of life. In clinical studies, fatigue was measured using functional assessment of chronic illness therapy-fatigue or FACIT-F and short form-36 or SF-36, physical component score instruments. These questionnaires can also be used to monitor improvement of fatigue following initiation of therapy. IL-1 inhibitors block the IL-1 signaling cascade, thereby preventing systemic inflammation in CAPS. The decrease in systemic inflammation is accompanied by improvement in fatigue.

Oral Escherichia coli Colonization Factor Antigen I (CFA/I) Fimbriae Ameliorate Arthritis via IL-35, not IL-27

PubMed Central

Kochetkova, Irina; Thornburg, Theresa; Callis, Gayle; Holderness, Kathryn; Maddaloni, Massimo; Pascual, David W.

2014-01-01

A Salmonella therapeutic expressing enterotoxigenic E. coli colonization factor antigen I (CFA/I) fimbriae protects against collagen-induced arthritis (CIA) by eliciting two regulatory T cell (Treg) subsets: TGF-β-producing Foxp3−CD39+CD4+ and IL-10-producing Foxp3+CD39+CD4+ T cells. However, it is unclear if CFA/I fimbriae alone are protective, and if other regulatory cytokines are involved especially in the context for the EBI3-sharing cytokines, Treg-derived IL-35 and APC-derived IL-27, both capable of suppressing Th17 cells and regulating autoimmune diseases. Subsequent evaluation revealed that a single oral dose of purified, soluble CFA/I fimbriae protected against CIA as effectively as Salmonella-CFA/I, and found Foxp3+CD39+CD4+ T cells as the source of secreted IL-35, whereas IL-27 production by CD11c+ cells was inhibited. Inquiring into their relevance, CFA/I fimbriae-treated IL-27 receptor-deficient (WSX-1−/−) mice were equally protected against CIA as wild-type mice suggesting a limited role for IL-27. In contrast, CFA/I fimbriae-mediated protection was abated in EBI3−/− mice accompanied by the loss of TGF-β- and IL-10-producing Tregs. Adoptive transfer of B6 CD39+CD4+ T cells to EBI3−/− mice with concurrent CFA/I plus IL-35 treatment effectively stimulated Tregs suppressing proinflammatory CII-specific Th cells. Opposingly, recipients co-transferred with B6 and EBI3−/− CD39+CD4+ T cells and treated with CFA/I plus IL-35 failed in protecting mice implicating the importance for endogenous IL-35 to confer CFA/I-mediated protection. Thus, CFA/I fimbriae stimulate IL-35 required for the co-induction of TGF-β and IL-10. PMID:24337375

Polymer and Surface Science in Europe, Israel, and Egypt: Some Observations,

DTIC Science & Technology

1981-11-25

BASCOM N UNCLASSIFIED ONRL-9 6-8 AL EndE~EE~hE 2.2 11 . 111 111111.5 1 . 4 ! 1 4 f ADA൑ 8 5 9 R-6-81 COND LDOW OFFICE Of, N A L POLYMER AND SURFACE...FORM 1 . REPORT NUMBER 12. GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED Polymer and...support or as participation in "sandwich" study programs. Under the sandwich system the student interrupts his studies after 1 to 2 yrs to spend 6 to 12

11β-HSD1 Modulates LPS-Induced Innate Immune Responses in Adipocytes by Altering Expression of PTEN

PubMed Central

Lai, Wenfang; Tian, Xue; Xiang, Qing; Chu, Kedan; Wei, Yicong; Deng, Jingti; Zhang, Shaoping; Brown, John

2015-01-01

Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) represents a therapeutic target for treating hyperglycemia in type 2 diabetes. Here, we investigate the effects of 11β-HSD1 on the innate immune response of adipocytes to produce proinflammatory cytokines. The 11β-HSD1 inhibitor emodin, or 11β-HSD1-targeted small interfering RNA, dose dependently suppressed IL-6, IL-1β, and TNF-α expression in lipopolysaccharide-treated 3T3-L1 adipocytes. Inhibiting 11β-HSD1 also reduced phosphatase and tensin homologue (PTEN) expression, a negative regulator of phosphatidylinositol 3-kinase effects, whereas 1pM cortisone or dexamethasone induced IL-6 and PTEN levels. PTEN-targeted small interfering RNA decreased IL-6, IL-1β, and TNF-α without affecting 11β-HSD1 levels. Correspondingly, emodin increased phosphorylated protein kinase B (p-PKB) (Ser473) to PKB ratio but not p-PKB (Thr308) to PKB ratio. Emodin did not increase the p-PKB (Ser473) to PKB ratio when the rapamycin-insensitive companion of mTOR was depleted, further supporting the involvement of mammalian target of rapamycin complex 2 in PKB phosphorylation. Moreover, emodin suppressed phosphorylated inhibitor of κB α (p-IκBα) to IκBα ratio and reduced nuclear factor κ B subunit p50 in the nuclear fraction. In contrast, 1pM cortisone or dexamethasone decreased p-PKB (Ser473) to PKB ratio, increased p-IκBα to IκBα ratio, and increased nuclear NF-κB subunit p50. Additionally, wortmannin had similar effects on IL-6, p-PKB (Ser473) to PKB ratio, and p-IκBα to IκBα ratio as 1pM cortisone or dexamethasone. Finally, emodin treatment of streptozotocin diabetic rats on a high-fat diet reduced levels of IL-6, PTEN, Cluster of Differentiation 68, and the ratio of p-IκBα to IκBα in visceral fat, indicating that our findings in vitro may also apply to visceral fat in vivo. Together, these results suggest that inhibiting 11β-HSD1 reduces lipopolysaccharide-induced proinflammatory innate

30 CFR 50.11 - Investigation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Investigation. 50.11 Section 50.11 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR ACCIDENTS, INJURIES, ILLNESSES..., ILLNESSES, EMPLOYMENT, AND COAL PRODUCTION IN MINES Notification, Investigation, Preservation of Evidence...

30 CFR 50.11 - Investigation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Investigation. 50.11 Section 50.11 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR ACCIDENTS, INJURIES, ILLNESSES..., ILLNESSES, EMPLOYMENT, AND COAL PRODUCTION IN MINES Notification, Investigation, Preservation of Evidence...

30 CFR 50.11 - Investigation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Investigation. 50.11 Section 50.11 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR ACCIDENTS, INJURIES, ILLNESSES..., ILLNESSES, EMPLOYMENT, AND COAL PRODUCTION IN MINES Notification, Investigation, Preservation of Evidence...

30 CFR 50.11 - Investigation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Investigation. 50.11 Section 50.11 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR ACCIDENTS, INJURIES, ILLNESSES..., ILLNESSES, EMPLOYMENT, AND COAL PRODUCTION IN MINES Notification, Investigation, Preservation of Evidence...

30 CFR 50.11 - Investigation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Investigation. 50.11 Section 50.11 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR ACCIDENTS, INJURIES, ILLNESSES..., ILLNESSES, EMPLOYMENT, AND COAL PRODUCTION IN MINES Notification, Investigation, Preservation of Evidence...

Rab11-FIP3 Regulation of Lck Endosomal Traffic Controls TCR Signal Transduction.

PubMed

Bouchet, Jérôme; Del Río-Iñiguez, Iratxe; Vázquez-Chávez, Elena; Lasserre, Rémi; Agüera-González, Sonia; Cuche, Céline; McCaffrey, Mary W; Di Bartolo, Vincenzo; Alcover, Andrés

2017-04-01

The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3). FIP3 overexpression or silencing and its ability to interact with Rab11 modify Lck subcellular localization and its delivery to the immunological synapse. Importantly, FIP3-dependent Lck localization controls early TCR signaling events, such as tyrosine phosphorylation of TCRζ, ZAP70, and LAT and intracellular calcium concentration, as well as IL-2 gene expression. Interestingly, FIP3 controls both steady-state and poststimulation phosphotyrosine and calcium levels. Finally, our findings indicate that FIP3 modulates TCR-CD3 cell surface expression via the regulation of steady-state Lck-mediated TCRζ phosphorylation, which in turn controls TCRζ protein levels. This may influence long-term T cell activation in response to TCR-CD3 stimulation. Therefore, our data underscore the importance of finely regulated endosomal traffic in TCR signal transduction and T cell activation leading to IL-2 production. Copyright © 2017 by The American Association of Immunologists, Inc.

[Eukaryotic expression of Leptospira interrogans lipL32/1-ompL1/1 fusion gene encoding genus-specific protein antigens and the immunoreactivity of expression products].

PubMed

Yan, Jie; Zhao, Shou-feng; Mao, Ya-fei; Ruan, Ping; Luo, Yi-hui; Li, Shu-ping; Li, Li-wei

2005-01-01

To construct the eukaryotic expression system of L.interrogans lipL32/1-ompL1/1 fusion gene and to identify the immunoreactivity of expression products. PCR with linking primer was used to construct the fusion gene lipL32/1-ompL1/1. The P.pastoris eukaryotic expression system of the fusion gene, pPIC9K-lipL32/1-ompL1/1-P. pastorisGS115, was constructed after the fusion gene was cloned and sequenced. Colony with phenotype His(+)Mut(+) was isolated by using MD and MM plates and His(+) Mut(+) transformant with high resistance to G418 was screened out by using YPD plate. Using lysate of His(+) Mut(+) colony with high copies of the target gene digested with yeast lyase as the template and 5'AOX1 and 3'AOX1 as the primers, the target fusion gene in chromosome DNA of the constructed P. pastoris engineering strain was detected by PCR. Methanol in BMMY medium was used to induce the target recombinant protein rLipL32/1-rOmpL1/1 expression. rLipL32/1-rOmpL1/1 in the medium supernatant was extracted by using ammonium sulfate precipitation and Ni-NTA affinity chromatography. Output and immunoreactivity of rLipL32/1-rOmpL1/1 were measured by SDS-PAGE and Western blot methods, respectively. Amplification fragments of the obtained fusion gene lipL32/1-ompL1/1 was 1794 bp in size. The homogeneity of nucleotide and putative amino acid sequences of the fusion gene were as high as 99.94 % and 100 %, respectively, compared with the sequences of original lipL32/1 and ompL1/1 genotypes. The constructed eukaryotic expression system was able to secrete rLipL32/1-rOmpL1/1 with an output of 10 % of the total proteins in the supernatant, which located the expected position after SDS-PAGE. The rabbit anti-rLipL32/1 and anti-rOmpL1/1 sera could combine the expressed rLipL32/1-rOmpL1/1. An eukaryotic expression system with high efficiency in P.pastoris of L.interrogans lipL32/1-ompL1/1 fusion gene was successfully constructed in this study. The expressed fusion protein shows specific

Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children.

PubMed

Wong, Hector R; Cvijanovich, Natalie Z; Hall, Mark; Allen, Geoffrey L; Thomas, Neal J; Freishtat, Robert J; Anas, Nick; Meyer, Keith; Checchia, Paul A; Lin, Richard; Bigham, Michael T; Sen, Anita; Nowak, Jeffrey; Quasney, Michael; Henricksen, Jared W; Chopra, Arun; Banschbach, Sharon; Beckman, Eileen; Harmon, Kelli; Lahni, Patrick; Shanley, Thomas P

2012-10-29

Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children. Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis. Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone. Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel

Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children

PubMed Central

2012-01-01

Introduction Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children. Methods Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis. Results Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone. Conclusions Genome-wide expression analysis has provided the foundation

Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models.

PubMed

Xu, Chunxiao; Zhang, Yanping; Rolfe, P Alexander; Hernández, Vivian M; Guzman, Wilson; Kradjian, Giorgio; Marelli, Bo; Qin, Guozhong; Qi, Jin; Wang, Hong; Yu, Huakui; Tighe, Robert; Lo, Kin-Ming; English, Jessie M; Radvanyi, Laszlo; Lan, Yan

2017-10-01

Purpose: To determine whether combination therapy with NHS-muIL12 and the anti-programmed death ligand 1 (PD-L1) antibody avelumab can enhance antitumor efficacy in preclinical models relative to monotherapies. Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt - mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice. Immune cell populations within spleen and tumors were evaluated by FACS and IHC. Immune gene expression in tumor tissue was profiled by NanoString® assay and plasma cytokine levels were determined by multiplex cytokine assay. The frequency of tumor antigen-reactive IFNγ-producing CD8 + T cells was evaluated by ELISpot assay. Results: NHS-muIL12 and avelumab combination therapy enhanced antitumor efficacy relative to either monotherapy in both tumor models. Most EMT-6 tumor-bearing mice treated with combination therapy had complete tumor regression. Combination therapy also induced the generation of tumor-specific immune memory, as demonstrated by protection against tumor rechallenge and induction of effector and memory T cells. Combination therapy enhanced cytotoxic NK and CD8 + T-cell proliferation and T-bet expression, whereas NHS-muIL12 monotherapy induced CD8 + T-cell infiltration into the tumor. Combination therapy also enhanced plasma cytokine levels and stimulated expression of a greater number of innate and adaptive immune genes compared with either monotherapy. Conclusions: These data indicate that combination therapy with NHS-muIL12 and avelumab increased antitumor efficacy in preclinical models, and suggest that combining NHS-IL12 and avelumab may be a promising approach to treating patients with solid tumors. Clin Cancer Res; 23(19); 5869-80. ©2017 AACR . ©2017 American Association for Cancer Research.

Muscle Glycogen Depletion Following 75-km of Cycling Is Not Linked to Increased Muscle IL-6, IL-8, and MCP-1 mRNA Expression and Protein Content

PubMed Central

Nieman, David C.; Zwetsloot, Kevin A.; Lomiwes, Dominic D.; Meaney, Mary P.; Hurst, Roger D.

2016-01-01

The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N = 20) participated in a 75-km cycling time trial (168 ± 26.0 min), with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2 ± 17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5 ± 2.8−, 45.3 ± 7.8−, and 8.25 ± 1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5 ± 14.1%, 347 ± 68.1%, and 148 ± 21.3%, respectively (all, P < 0.001). Serum myoglobin and cortisol increased 32.1 ± 3.3 to 242 ± 48.3 mg/mL, and 295 ± 27.6 to 784 ± 63.5 nmol/L, respectively (both P < 0.001). Plasma IL-6, IL-8, and MCP-1 increased 0.42 ± 0.07 to 18.5 ± 3.8, 4.07 ± 0.37 to 17.0 ± 1.8, and 96.5 ± 3.7 to 240 ± 21.6 pg/mL, respectively (all P < 0.001). Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r = 0.462, P = 0.040), with change in myoglobin related to plasma IL-8 (r = 0.582, P = 0.007) and plasma MCP-1 (r = 0.457, P = 0.043), and muscle MCP-1 protein (r = 0.588, P = 0.017); cortisol was related to plasma IL-8 (r = 0.613, P = 0.004), muscle IL-8 protein (r = 0.681, P = 0.004), and plasma MCP-1 (r = 0.442, P = 0.050). In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1. PMID:27729872

Regulation of IL-17 Family Members by Adrenal Hormones During Experimental Sepsis in Mice

PubMed Central

Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D.; Sarma, J. Vidya; Zetoune, Firas S.; Ward, Peter A.

2014-01-01

Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. PMID:23499051

Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice.

PubMed

Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D; Sarma, J Vidya; Zetoune, Firas S; Ward, Peter A

2013-04-01

Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Tumor-targeted IL-2 amplifies T cell-mediated immune response induced by gene therapy with single-chain IL-12

PubMed Central

Lode, Holger N.; Xiang, Rong; Duncan, Steven R.; Theofilopoulos, Argyrios N.; Gillies, Stephen D.; Reisfeld, Ralph A.

1999-01-01

Induction, maintenance, and amplification of tumor-protective immunity after cytokine gene therapy is essential for the clinical success of immunotherapeutic approaches. We investigated whether this could be achieved by single-chain IL-12 (scIL-12) gene therapy followed by tumor-targeted IL-2 using a fusion protein containing a tumor-specific recombinant anti-ganglioside GD2 antibody and IL-2 (ch14.18-IL-2) in a poorly immunogenic murine neuroblastoma model. Herein, we demonstrate the absence of liver and bone marrow metastases after a lethal challenge with NXS2 wild-type cells only in mice (five of six animals) vaccinated with scIL-12-producing NXS2 cells and given a booster injection of low-dose ch14.18-IL-2 fusion protein. This tumor-protective immunity was effective 3 months after initial vaccination, in contrast to control animals treated with a nonspecific fusion protein or an equivalent mixture of antibody and IL-2. Only vaccinated mice receiving the tumor-specific ch14.18-IL-2 fusion protein revealed a reactivation of CD8+ T cells and subsequent MHC class I-restricted tumor target cell lysis in vitro. The sequential increase in the usage of TCR chains Vβ11 and -13 in mouse CD8+ T cells after vaccination and amplification with ch14.18-IL-2 suggests that the initial polyclonal CD8+ T cell response is effectively boosted by targeted IL-2. In conclusion, we demonstrate that a successful boost of a partially protective memory T cell immune response that is induced by scIL-12 gene therapy could be generated by tumor-specific targeting of IL-2 with a ch14.18-IL-2 fusion protein. This approach could increase success rates of clinical cancer vaccine trials. PMID:10411920

Therapeutically blocking Interleukin-11 Receptor-α enhances doxorubicin cytotoxicity in high grade type I endometrioid tumours.

PubMed

Winship, Amy; Van Sinderen, Michelle; Rainczuk, Katarzyna; Dimitriadis, Evdokia

2017-04-04

High grade type I endometrial cancers have poor prognosis. Interleukin (IL)11 is elevated in tumours and uterine lavage with increasing tumour grade in women. IL11 regulates cell cycle, invasion and migration and we recently demonstrated that IL11 receptor (R)α inhibition impaired low and moderate grade endometrial tumourigenesis in vivo. In this report, we hypothesized that micro-RNA(miR)-1 regulates IL11 and that IL11 promotes high grade endometrial tumour growth. We aimed to determine whether combination treatment using an anti-human IL11Rα blocking antibody (Ab) and doxorubicin chemotherapeutic impairs high grade tumour growth. MiR-1 was absent in human endometrial tumours versus human benign endometrium (n = 10/group). Transfection with miR-1 mimic restored miR-1 expression, down-regulated IL11 mRNA and impaired cell viability in grade 3-derived AN3CA human endometrial epithelial cancer cells. AN3CA cell proliferation was reduced in response to Ab and doxorubicin combination treatment versus Ab, IgG control, or doxorubicin alone. Subcutaneous xenograft tumours were established in female Balb/c athymic nude mice using AN3CA cells expressing IL11 and IL11Rα. Administration of recombinant human IL11 to mice (n = 4/group) activated IL11 downstream target, signal transducers and activators of transcription (STAT3) and significantly increased tumour growth (p < 0.05), suggesting that IL11 promotes high grade tumour growth. IL11Rα blocking Ab reduced STAT3 phosphorylation and combination treatment with doxorubicin resulted in a significant reduction in tumour growth (p < 0.05) compared to Ab, doxorubicin, or IgG control. Our data suggest that therapeutically targeting IL11Rα in combination with doxorubicin chemotherapy could inhibit high grade type I endometrioid cancer growth.

Production of interleukin-2 (IL-2) and expression of IL-2 receptor in patients with IgA nephropathy.

PubMed

Lee, T W; Kim, M J

1992-01-01

IL-2 production has been measured in several disease including type I diabetes mellitus, systemic lupus erythematosus, acquired immunodeficiency syndrome and active pulmonary sarcoidosis and its pathogenetic role was suggested. In IgA nephropathy, altered T cell subsets were reported to be associated with increased synthesis of IgA. The altered IL-2 production and the expression of IL-2 receptor might be involved in the pathogenesis of IgA nephropathy. To investigate the role of T cell mediated immunity in the pathogenesis of IgA nephropathy, the immune parameters such as T cell subsets, NK cell activity, interleukin-2 (IL-2) production and IL-2 receptor expression on peripheral blood mononuclear cells (PBMC) were measured before and/or after phytohemagglutinin (PHA) stimulation in 15 patients with IgA nephropathy. Age and sex matched 15 healthy controls and the correlations between the IL-2 production and immune parameters were evaluated. The mean percentages of T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio of the patients were not different from those of controls and the proportions of CD8 CD11b cell in the patients (21.0 +/- 3.6%) were significantly lower than those in controls (30.5 +/- 5.3%) (p < 0.005). The production of IL-2 by fresh PBMC of both patients and controls was in undetectable ranges. The production of IL-2 by PHA stimulated PBMC of patients was significantly higher than that of controls (140.03 +/- 43.2 U/ml vs 106.5 +/- 42.1 U/ml, p < 0.05). The proportions of lymphocytes expressing the IL-2 receptor (CD25) before the stimulation with PHA in patients were 1.22 +/- 1.00 percent and were not different from those in controls (1.12 +/- 0.78 percent). The correlations between the production of IL-2 and the concentrations of serum IgA, the degrees of histologic alterations and the proportions of CD8 and CD8CD11b cells were not significant. There was a weak tendency of a positive correlation (p < 0.1) between

Enhancing Interleukin-6 and Interleukin-11 receptor cleavage.

PubMed

Lokau, Juliane; Wandel, Marieke; Garbers, Christoph

2017-04-01

Proteolytic cleavage of the membrane-bound Interleukin-6 receptor (IL-6R) by the metalloprotease ADAM17 releases an agonistic soluble form of the IL-6R (sIL-6R), which is responsible for the pro-inflammatory trans-signaling branch of the cytokine's activities. This proteolytic step, which is also called ectodomain shedding, is critically regulated by the cleavage site within the IL-6R stalk, because mutations or small deletions within this region are known to render the IL-6R irresponsive towards proteolysis. In the present study, we employed cleavage site profiling data of ADAM17 to generate an IL-6R with increased cleavage susceptibility. Using site-directed mutagenesis, we showed that the non-prime sites P3 and P2 and the prime site P1' were critical for this increase in proteolysis, whereas other positions within the cleavage site were of minor importance. Insertion of this optimized cleavage site into the stalk of the Interleukin-11 receptor (IL-11R) was not sufficient to enable ADAM17-mediated proteolysis, but transfer of different parts of the IL-6R stalk enabled shedding by ADAM17. These findings shed light on the cleavage site specificities of ADAM17 using a native substrate and reveal further differences in the proteolysis of IL-6R and IL-11R. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mid-trimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, TNF-α, and lipopolysaccharide binding protein in normal pregnancies: a prospective evaluation according to parity, gestational age, and fetal gender.

PubMed

Bamberg, Christian; Fotopoulou, Christina; Linder, Mattea; Roehr, Charles Christoph; Dudenhausen, Joachim W; Henrich, Wolfgang; Kalache, Karim

2011-07-01

To assess mid-trimester amniotic fluid concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender. Cytokine concentrations were measured within a week of amniocentesis during GW 15+0 to 20+6 and correlated with GW at birth, parity, and fetal gender. After exclusion of women with an adverse pregnancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0-5). Ranges for IL-6, IL-8, TNF-α, and LBP were 4.9-2620 pg/mL, 36.2-5843 pg/mL, 8.0-28.2 pg/mL, and 0.06-1.9 μg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-α values did between the 15(th) and 16(th) and the 15(th) and 18(th) weeks of gestation (P<0.05). No significant correlations between cytokine levels and parity or fetal gender were identified. Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-α concentrations. Further analyses are warranted to establish the role of cytokines in predicting adverse pregnancy outcomes.

An efficient preparation of labelling precursor of [11C]L-deprenyl-D2 and automated radiosynthesis.

PubMed

Zirbesegger, Kevin; Buccino, Pablo; Kreimerman, Ingrid; Engler, Henry; Porcal, Williams; Savio, Eduardo

2017-01-01

The synthesis of [ 11 C]L-deprenyl-D 2 for imaging of astrocytosis with positron emission tomography (PET) in neurodegenerative diseases has been previously reported. [ 11 C]L-deprenyl-D 2 radiosynthesis requires a precursor, L-nordeprenyl-D 2 , which has been previously synthesized from L-amphetamine as starting material with low overall yields. Here, we present an efficient synthesis of L-nordeprenyl-D 2 organic precursor as free base and automated radiosynthesis of [ 11 C]L-deprenyl-D 2 for PET imaging of astrocytosis. The L-nordeprenyl-D 2 precursor was synthesized from the easily commercial available and cheap reagent L-phenylalanine in five steps. Next, N -alkylation of L-nordeprenyl-D 2 free base with [ 11 C]MeOTf was optimized using the automated commercial platform GE TRACERlab® FX C Pro. A simple and efficient synthesis of L-nordeprenyl-D 2 precursor of [ 11 C]L-deprenyl-D 2 as free base has been developed in five synthetic steps with an overall yield of 33%. The precursor as free base has been stable for 9 months stored at low temperature (-20 °C). The labelled product was obtained with 44 ± 13% ( n  = 12) (end of synthesis, decay corrected) radiochemical yield from [ 11 C]MeI after 35 min synthesis time. The radiochemical purity was over 99% in all cases and specific activity was (170 ± 116) GBq/μmol. A high-yield synthesis of [ 11 C]L-deprenyl-D 2 has been achieved with high purity and specific activity. L-nordeprenyl-D 2 precursor as free amine was applicable for automated production in a commercial synthesis module for preclinical and clinical application.

Psychosocial well-being in young adults with chronic illness since childhood: the role of illness cognitions

PubMed Central

2014-01-01

Background More and more pediatric patients reach adulthood. Some of them are successfully integrating in adult life, but many others are not. Possibly Illness cognitions (IC) - the way people give meaning to their illness/disability – may play a role in individual differences on long-term adjustment. This study explored the association of IC with disease–characteristics and Health Related Quality of Life (HRQoL), anxiety and depression in young adults with a disability benefit due to childhood-onset chronic condition. Methods In a cross-sectional study, young adults (22–31 years, N = 377) who claimed a disability benefit because of a somatic condition since childhood, completed the Illness Cognition Questionnaire (acceptance-helplessness-benefits), RAND-36 (HRQoL) and HADS (anxiety and depression) online. Besides descriptive statistics, linear regression analyses were conducted to predict (1) illness cognitions by age, gender and disease-characteristics, and (2) HRQoL (Mental and Physical Component Scale), Anxiety and Depression by illness cognitions, controlling for disease-characteristics, age and gender. Results Respectively 90.2%, 83.8% and 53.3% of the young adults with a disability benefit experienced feelings of acceptance, benefits and helplessness. Several disease-characteristics were associated with IC. More acceptance and less helplessness were associated with better mental (β = 0.31; β = −0.32) and physical (β = 0.16; β = −0.15) HRQoL and with less anxiety (β = −0.27; β = 0.28) and depression (β = −0.29; β = 0.31). Conclusions IC of young adult beneficiaries were associated with their HRQoL and feelings of anxiety and depression. Early recognition of psychological distress and negative IC might be a key to the identification of pediatric patients at risk for long-term dysfunction. Identification of maladaptive illness cognitions enables the development of psychosocial interventions to optimise

High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.

PubMed

Zahorchak, Alan F; Macedo, Camila; Hamm, David E; Butterfield, Lisa H; Metes, Diana M; Thomson, Angus W

2018-01-01

Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4 + and CD8 + T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8 + T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Dexamethasone antagonizes IL-4 and IL-10-induced release of IL-1RA by monocytes but augments IL-4-, IL-10-, and TGF-beta-induced suppression of TNF-alpha release.

PubMed

Joyce, D A; Steer, J H; Kloda, A

1996-07-01

The activities of monocyte-derived tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta are potentially modified by IL-1RA and soluble receptors for TNF (sTNF-R), which are themselves monocyte products. IL-4, IL-10, TGF-beta, and glucocorticoids (GC) all suppress the lipopolysaccharide (LPS)-stimulated release of TNF-alpha and IL-1beta but vary in their effects on IL-1RA and sTNF-R. This raises the prospect of interactions between the cytokines and glucocorticoids, which may be antagonistic or additive on IL-1 and TNF activity. We, therefore, studied the interactions of the GC dexamethasone (Dex) with IL-4, IL-10, and transforming growth factor (TGF)-beta on the release of TNF-alpha and IL-1RA by human monocytes and the monocytic THP-1 cell line. Low concentration of Dex (10(-8)-10(-7)M) acted additively with low concentrations of IL-4 (0.01-1 ng/ml), IL-10 (0.01-0.1 U/ml), or TGF-beta (0.01-1 ng/ml) to profoundly suppress LPS-stimulated release of TNF-alpha by whole blood and, to a lesser degree, THP-1 cells. Dex also suppressed spontaneous release of IL-1RA from PBMC and THP-1 cells, whereas IL-4 and IL-10, but not TGF-beta, stimulated release. Dex antagonized the enhanced release in IL-4 and IL-10-stimulated cultures. The capacity to stimulate release of IL-1RA may contribute to the anti-inflammatory potential of IL-4 and IL-10 in monocyte/macrophage-mediated disease. GC, therefore, do not uniquely enhance the suppressive functions of IL-4 and IL-10 on monokine activity. The therapeutic benefit of combinations of GC and IL-4, IL-10 or TGF-beta in disease may depend on the roles of the individual monokines and antagonists in pathogenesis.

11. Historic American Buildings Survey Allen L. Hubbard, Photographer December ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. Historic American Buildings Survey Allen L. Hubbard, Photographer December 1, 1936 SOUTHWEST CORNER ROOM (2nd floor, east wall) - Fort Western, Main Building, Bowman Street, Augusta, Kennebec County, ME

[Brd3 promotes IL-6 production via enhancing acetylase CBP recruitment and histone 3 acetylation within IL6 promoter].

PubMed

Ren, Wenhui; Sun, Donghao; Wang, Chunmei; Li, Nan

2016-10-01

Objective To investigate the role of bromodomain containing 3 (Brd3) in LPS-triggered interleukin-6 (IL-6) production in macrophages and the underlying mechanism. Methods CRISPR-Cas9 technology was used to screen an RAW264.7 cell line with Brd3 knockout (Brd3 -/- ). The Brd3 -/- cells were used as an experimental group, and the parential cells expressing wide-type Brd3 as a control group. The IL-6 level in cell culture supernatant was detected by ELISA after 100 ng/mL LPS challenging. Effect of Brd3 knockout on the expression and activation of signal pathways involved in IL-6 expression, including the NF-κB and mitogen-activated protein kinase (MAPK) pathways were examined by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to evaluate the recruitment of acetylase CREB-binding protein (CBP) to IL6 gene promoter and the acetylation level of histone 3 within IL6 gene promoter. Results LPS treatment significantly downregulated Brd3 expression in mouse peritoneal macrophages. LPS-induced production of IL-6 was significantly inhibited in Brd3 -/- macrophages. The expressions and activation of signal molecules within NF-κB and MAPK pathways were barely affected. Brd3 knockout significantly decreased the recruitment of acetylase CBP to IL6 gene promoter, and the acetylation level of histone3 within IL6 gene promoter was also repressed. Conclusion Brd3 promotes LPS-triggered IL-6 production via promoting the recruitment of CBP to IL6 promoter and enhancing the acetylation level of histone 3 within IL6 promoter.

Acute Pesticide Illnesses Associated with Off-Target Pesticide Drift from Agricultural Applications: 11 States, 1998–2006

PubMed Central

Lee, Soo-Jeong; Mehler, Louise; Beckman, John; Diebolt-Brown, Brienne; Prado, Joanne; Lackovic, Michelle; Waltz, Justin; Mulay, Prakash; Schwartz, Abby; Mitchell, Yvette; Moraga-McHaley, Stephanie; Gergely, Rita

2011-01-01

Background: Pesticides are widely used in agriculture, and off-target pesticide drift exposes workers and the public to harmful chemicals. Objective: We estimated the incidence of acute illnesses from pesticide drift from outdoor agricultural applications and characterized drift exposure and illnesses. Methods: Data were obtained from the National Institute for Occupational Safety and Health’s Sentinel Event Notification System for Occupational Risks–Pesticides program and the California Department of Pesticide Regulation. Drift included off-target movement of pesticide spray, volatiles, and contaminated dust. Acute illness cases were characterized by demographics, pesticide and application variables, health effects, and contributing factors. Results: From 1998 through 2006, we identified 2,945 cases associated with agricultural pesticide drift from 11 states. Our findings indicate that 47% were exposed at work, 92% experienced low-severity illness, and 14% were children (< 15 years). The annual incidence ranged from 1.39 to 5.32 per million persons over the 9-year period. The overall incidence (in million person-years) was 114.3 for agricultural workers, 0.79 for other workers, 1.56 for nonoccupational cases, and 42.2 for residents in five agriculture-intensive counties in California. Soil applications with fumigants were responsible for the largest percentage (45%) of cases. Aerial applications accounted for 24% of cases. Common factors contributing to drift cases included weather conditions, improper seal of the fumigation site, and applicator carelessness near nontarget areas. Conclusions: Agricultural workers and residents in agricultural regions had the highest rate of pesticide poisoning from drift exposure, and soil fumigations were a major hazard, causing large drift incidents. Our findings highlight areas where interventions to reduce off-target drift could be focused. PMID:21642048

Increased interleukin-11 levels in thoracic aorta and plasma from patients with acute thoracic aortic dissection.

PubMed

Xu, Yao; Ye, Jing; Wang, Menglong; Wang, Yuan; Ji, Qingwei; Huang, Ying; Zeng, Tao; Wang, Zhen; Ye, Di; Jiang, Huimin; Liu, Jianfang; Lin, Yingzhong; Wan, Jun

2018-06-01

Interleukin (IL) 11 is closely related to tumor and hematological system diseases. Recent studies have demonstrated that IL-11 also participates in cardiovascular diseases, including ischemia-reperfusion mediated heart injury and acute myocardial infarction. This study aimed to investigate whether IL-11 is involved in acute thoracic aortic dissection (TAD). Aortic tissue samples from normal donors and acute TAD patients were collected, and the expression of IL-11 in all aortic tissue was analyzed. In addition, blood samples from patients with chest pain were collected and divided into a non-AD (NAD) group and a TAD group according to the results of computed tomography angiography of the thoracic aorta. The plasma IL-11, IL-17 and interferon (IFN) γ in all blood samples were measured. Compared with aortic tissue of normal controls, IL-11 was significantly increased in aortic tissue of acute TAD patients, especially in the torn section. The IL-11 was derived from aorta macrophages in TAD. In addition, the plasma IL-11, IL-17 and IFN-γ were significantly higher in acute TAD patients than in NAD patients, and the correlation analysis showed that IL-11 levels were positively correlated with levels of IFN-γ, IL-17, glucose, systolic blood pressure, diastolic blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that elevated IL11 in patients who may have diagnostic value of TAD, but less that D-dimer. IL-11 was increased in thoracic aorta and plasma of TAD patients and may be a promising biomarker for diagnosis in patients with TAD. Copyright © 2018. Published by Elsevier B.V.

IL-23 (Interleukin-23)-Producing Conventional Dendritic Cells Control the Detrimental IL-17 (Interleukin-17) Response in Stroke.

PubMed

Gelderblom, Mathias; Gallizioli, Mattia; Ludewig, Peter; Thom, Vivien; Arunachalam, Priyadharshini; Rissiek, Björn; Bernreuther, Christian; Glatzel, Markus; Korn, Thomas; Arumugam, Thiruma Valavan; Sedlacik, Jan; Gerloff, Christian; Tolosa, Eva; Planas, Anna M; Magnus, Tim

2018-01-01

Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood. In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels. We used conditional DC depletion, bone marrow chimeric mice, and IL-23 (interleukin-23) receptor-deficient mice to further explore the functional role of DCs. We show that the ischemic brain was rapidly infiltrated by IRF4 + /CD172a + conventional type 2 DCs and that conventional type 2 DCs were the most abundant subset in comparison with all other DC subsets. Twenty-four hours after ischemia onset, conventional type 2 DCs became the major source of IL-23, promoting neutrophil infiltration by induction of IL-17 (interleukin-17) in γδ T cells. Functionally, the depletion of CD11c + cells or the genetic disruption of the IL-23 signaling abrogated both IL-17 production in γδ T cells and neutrophil infiltration. Interruption of the IL-23/IL-17 cascade decreased infarct size and improved neurological outcome after stroke. Our results suggest a central role for interferon regulatory factor 4-positive IL-23-producing conventional DCs in the IL-17-dependent secondary tissue damage in stroke. © 2017 American Heart Association, Inc.

β-Glucans in food modify colonic microflora by inducing antimicrobial protein, calprotectin, in a Dectin-1-induced-IL-17F-dependent manner.

PubMed

Kamiya, T; Tang, C; Kadoki, M; Oshima, K; Hattori, M; Saijo, S; Adachi, Y; Ohno, N; Iwakura, Y

2018-05-01

Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a -/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c + /CD11b + myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a -/- and Il17f -/- mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with β-glucan-free food. These observations suggest that food-derived β-glucans control the specific commensal microbiota via the Dectin-1-IL-17F-calprotectin axis to maintain the intestinal homeostasis.

Mental Illness and Mental Healthcare Receipt among Hospitalized Veterans with Serious Physical Illnesses.

PubMed

Garrido, Melissa M; Prigerson, Holly G; Neupane, Suvam; Penrod, Joan D; Johnson, Christopher E; Boockvar, Kenneth S

2017-03-01

Psychosocial distress among patients with limited life expectancy influences treatment decisions, treatment adherence, and physical health. Veterans may be at elevated risk of psychosocial distress at the end of life, and understanding their mental healthcare needs may help identify hospitalized patients to whom psychiatric services should be targeted. To examine mental illness prevalence and mental health treatment rates among a national sample of hospitalized veterans with serious physical illnesses. Design, Subjects, and Measurements: This was a retrospective study of 11,286 veterans hospitalized in a Veterans Health Administration acute care facility in fiscal year 2011 with diagnoses of advanced cancer, congestive heart failure, chronic obstructive pulmonary disease, and/or advanced HIV/AIDS. Prevalent and incident mental illness diagnoses during and before hospitalization and rates of psychotherapy and psychotropic use among patients with incident depression and anxiety were measured. At least one-quarter of the patients in our sample had a mental illness or substance use disorder. The most common diagnoses at hospitalization were depression (11.4%), followed by alcohol abuse or dependence (5.5%), and post-traumatic stress disorder (4.9%). Of the 831 patients with incident past-year depression and 258 with incident past-year anxiety, nearly two-thirds received at least some psychotherapy or guideline-concordant medication within 90 days of diagnosis. Of 191 patients with incident depression and 47 with incident anxiety at time of hospitalization, fewer than half received mental healthcare before discharge. Many veterans hospitalized with serious physical illnesses have comorbid mental illnesses and may benefit from depression and anxiety treatment.

Differential antioxidative responses to dehydration-induced oxidative stress in core set of foxtail millet cultivars [Setaria italica (L.)].

PubMed

Lata, Charu; Jha, Sarita; Dixit, Vivek; Sreenivasulu, Nese; Prasad, Manoj

2011-10-01

Foxtail millet (Setaria italica L.) known as a relatively drought-tolerant crop across the world is grown in arid and semi-arid regions. To the best of our knowledge, no systematic study on drought tolerance screening of foxtail millet germplasm being a drought-tolerant crop has been reported so far. To explore genetic diversity of drought-induced oxidative stress tolerance in foxtail millet, we employed lipid peroxidation measure to assess membrane integrity under stress as biochemical marker to screen 107 cultivars and classified the genotypes as highly tolerant, tolerant, sensitive, and highly sensitive. From this comprehensive screening, four cultivars showing differential response to dehydration tolerance were selected to understand the physiological and biochemical basis of tolerance mechanisms. The dehydration-tolerant cultivars (IC-403579 and Prasad) showed considerably lower levels of lipid peroxidation and electrolyte leakage as compared with dehydration-sensitive cultivars (IC-480117 and Lepakshi), indicating better cell membrane integrity in tolerant cultivars. Correspondingly, tolerant genotypes maintained higher activity of catalase (EC 1.11.1.6), ascorbate peroxidase (APX; EC 1.11.1.11), and glutathione reductase (GR; EC 1.6.4.2) across different time-course period of polyethylene glycol (PEG) treatments in comparison to sensitive ones. The above biochemical results were further validated through quantitative real-time PCR analysis of APX and GR, whose transcripts were substantially induced by PEG treatments in tolerant cultivars. These results suggest that tolerant cultivars possess wider array of antioxidant machinery with efficient ascorbate-glutathione pathway to cope with drought-induced oxidative stress.

The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumonia.

PubMed

de Brito, Rita de Cássia Coelho Moraes; Lucena-Silva, Norma; Torres, Leuridan Cavalcante; Luna, Carlos Feitosa; Correia, Jaílson de Barros; da Silva, Giselia Alves Pontes

2016-12-01

To identify markers for earlier diagnosis of severe pneumonia, we assess the correlation between serum cytokine profile of children with different pneumonia severity. In 25 hospitalized children, 7 with mild pneumonia and 18 with severe pneumonia, the serum concentration of 11 cytokines in three sampling times were dosed. Statistical analysis included parametric and non-parametric tests, Pearson correlation and ROC curve for cut-off definition of cytokines. At admission, IL-6 serum levels were high in mild or severe pneumonia, and was associated to vomiting (P = 0.019) in both groups; and also to dyspnea (P = 0.012) and white blood cell count (P = 0.045) in patients with severe pneumonia. IL-10 levels were also high in patients with pneumonia and were associated to lymphocytosis (P = 0.025). The ROC curve of the IL-6:IL-10 serum levels ratio discriminated severe pneumonia cases at admission, and persistence of infection in the third day of antibiotic therapy, with positive predictive values of 93% and 89%, respectively. The balance between IL-6 and IL-10 serum levels showed to be a more discriminative marker for severity definition and evaluation of recovery in patients with pneumonia.

A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-γ and IFN-λ) and Type 2 Inflammation (IL-5 and IL-13).

PubMed

Hansel, Trevor T; Tunstall, Tanushree; Trujillo-Torralbo, Maria-Belen; Shamji, Betty; Del-Rosario, Ajerico; Dhariwal, Jaideep; Kirk, Paul D W; Stumpf, Michael P H; Koopmann, Jens; Telcian, Aurica; Aniscenko, Julia; Gogsadze, Leila; Bakhsoliani, Eteri; Stanciu, Luminita; Bartlett, Nathan; Edwards, Michael; Walton, Ross; Mallia, Patrick; Hunt, Toby M; Hunt, Trevor L; Hunt, Duncan G; Westwick, John; Edwards, Matthew; Kon, Onn Min; Jackson, David J; Johnston, Sebastian L

2017-05-01

Rhinovirus infection is a major cause of asthma exacerbations. We studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations. We used nasosorption on days 0, 2-5 and 7 and bronchosorption at baseline and day 4 to sample mucosal lining fluid to investigate airway mucosal responses to rhinovirus infection in patients with allergic asthma (n=28) and healthy non-atopic controls (n=11), by using a synthetic absorptive matrix and measuring levels of 34 cytokines and chemokines using a sensitive multiplex assay. Following rhinovirus infection asthmatics developed more upper and lower respiratory symptoms and lower peak expiratory flows compared to controls (all P<0.05). Asthmatics also developed higher nasal lining fluid levels of an anti-viral pathway (including IFN-γ, IFN-λ/IL-29, CXCL11/ITAC, CXCL10/IP10 and IL-15) and a type 2 inflammatory pathway (IL-4, IL-5, IL-13, CCL17/TARC, CCL11/eotaxin, CCL26/eotaxin-3) (area under curve day 0-7, all P<0.05). Nasal IL-5 and IL-13 were higher in asthmatics at day 0 (P<0.01) and levels increased by days 3 and 4 (P<0.01). A hierarchical correlation matrix of 24 nasal lining fluid cytokine and chemokine levels over 7days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-γ, CXCL10/IP10, CXCL11/ITAC, IL-15 and IL-5 increased in bronchial lining fluid following viral infection (all P<0.05). Precision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

U.S. EPA, Pesticide Product Label, SBP-1382/ESOBIOTHRIN/P.B.O INSEC. AEROSOL 0.2% + 0.3% + 1.2% FORMULA, 10/14/1988

EPA Pesticide Factsheets

2011-04-14

... 11,.,1., PlllCAm .. uy "Innall lua_" •• 1 ••• _ •••• IIC 111111'" CAIn I III 0S • .,.. ... II..... T... ..I' ••• 1 .... _ ." , ,I •• ,.bl? a • .... 2 ..... __ ~ ... ...

Rhabdomyolysis in Critically Ill Surgical Patients

PubMed Central

Kuzmanovska, Biljana; Cvetkovska, Emilija; Kuzmanovski, Igor; Jankulovski, Nikola; Shosholcheva, Mirjana; Kartalov, Andrijan; Spirovska, Tatjana

2016-01-01

Introduction: Rhabdomyolysis is a syndrome of injury of skeletal muscles associated with myoglobinuria, muscle weakness, electrolyte imbalance and often, acute kidney injury as severe complication. The aim: of this study is to detect the incidence of rhabdomyolysis in critically ill patients in the surgical intensive care unit (ICU), and to raise awareness of this medical condition and its treatment among the clinicians. Material and methods: A retrospective review of all surgical and trauma patients admitted to surgical ICU of the University Surgical Clinic “Mother Teresa” in Skopje, Macedonia, from January 1st till December 31st 2015 was performed. Patients medical records were screened for available serum creatine kinase (CK) with levels > 200 U/l, presence of myoglobin in the serum in levels > 80 ng/ml, or if they had a clinical diagnosis of rhabdomyolysis by an attending doctor. Descriptive statistical methods were used to analyze the collected data. Results: Out of totally 1084 patients hospitalized in the ICU, 93 were diagnosed with rhabdomyolysis during the course of one year. 82(88%) patients were trauma patients, while 11(12%) were surgical non trauma patients. 7(7.5%) patients diagnosed with rhabdomyolysis developed acute kidney injury (AKI) that required dialysis. Average values of serum myoglobin levels were 230 ng/ml, with highest values of > 5000 ng/ml. Patients who developed AKI had serum myoglobin levels above 2000 ng/ml. Average values of serum CK levels were 400 U/l, with highest value of 21600 U/l. Patients who developed AKI had serum CK levels above 3000 U/l. Conclusion: Regular monitoring and early detection of elevated serum CK and myoglobin levels in critically ill surgical and trauma patients is recommended in order to recognize and treat rhabdomyolysis in timely manner and thus prevent development of AKI. PMID:27703296

Rhabdomyolysis in Critically Ill Surgical Patients.

PubMed

Kuzmanovska, Biljana; Cvetkovska, Emilija; Kuzmanovski, Igor; Jankulovski, Nikola; Shosholcheva, Mirjana; Kartalov, Andrijan; Spirovska, Tatjana

2016-07-27

Rhabdomyolysis is a syndrome of injury of skeletal muscles associated with myoglobinuria, muscle weakness, electrolyte imbalance and often, acute kidney injury as severe complication. of this study is to detect the incidence of rhabdomyolysis in critically ill patients in the surgical intensive care unit (ICU), and to raise awareness of this medical condition and its treatment among the clinicians. A retrospective review of all surgical and trauma patients admitted to surgical ICU of the University Surgical Clinic "Mother Teresa" in Skopje, Macedonia, from January 1 st till December 31 st 2015 was performed. Patients medical records were screened for available serum creatine kinase (CK) with levels > 200 U/l, presence of myoglobin in the serum in levels > 80 ng/ml, or if they had a clinical diagnosis of rhabdomyolysis by an attending doctor. Descriptive statistical methods were used to analyze the collected data. Out of totally 1084 patients hospitalized in the ICU, 93 were diagnosed with rhabdomyolysis during the course of one year. 82(88%) patients were trauma patients, while 11(12%) were surgical non trauma patients. 7(7.5%) patients diagnosed with rhabdomyolysis developed acute kidney injury (AKI) that required dialysis. Average values of serum myoglobin levels were 230 ng/ml, with highest values of > 5000 ng/ml. Patients who developed AKI had serum myoglobin levels above 2000 ng/ml. Average values of serum CK levels were 400 U/l, with highest value of 21600 U/l. Patients who developed AKI had serum CK levels above 3000 U/l. Regular monitoring and early detection of elevated serum CK and myoglobin levels in critically ill surgical and trauma patients is recommended in order to recognize and treat rhabdomyolysis in timely manner and thus prevent development of AKI.

Duplicate Record Elimination in Large Data Files.

DTIC Science & Technology

1981-08-01

UNCLASSIFIJED CSTR -445 NL LmEE~hhE - I1.0 . 111112----5 1.~4 __112 ___IL25_ 1.4 111111.6 EI24 COMPUTER SCIENCES DEPARTMENT oUniversity of Wisconsin...we propose a combinatorial model for the use in the analysis of algorithms for duplicate elimination. We contend that this model can serve as a...duplicates in a multiset of records, knowing the size of the multiset and the number of distinct records in it. 3. Algorithms for Duplicate Elimination

Atopic dermatitis patients carrying G allele in -1082 G/A IL-10 polymorphism are predisposed to higher serum concentration of IL-10.

PubMed

Lesiak, Aleksandra; Zakrzewski, Marcin; Przybyłowska, Karolina; Rogowski-Tylman, Michał; Wozniacka, Anna; Narbutt, Joanna

2014-12-22

Atopic dermatitis (AD) is a chronic skin inflammatory disease in which Th2-derived cytokines play an essential role. Aim of the study was to assess interleukin 4, 10 and 13 (IL-4, IL-10 and IL-13) serum concentrations in AD patients and to correlate the values with the occurrence of genotypes of selected polymorphisms in genes encoding these cytokines. Seventy-six AD patients (mean age 11.4 years) and 60 healthy controls were enrolled in the study. Blood samples were analyzed for IL-4, IL-10 and IL-13 concentrations with ELISA assay and genotyping for -590C/T IL-4, -1082A/G IL-10 and -1055C/T IL-13 polymorphisms with PCR-RFLP. The obtained results revealed statistically higher serum concentration of IL-10 and IL-13 in AD patients when compared to healthy controls (10.30 pg/ml vs. 8.51 pg/ml for IL-10 and 5.67 pg/ml vs. 4.98 pg/ml for IL-13). There were no significant differences between AD patients and controls in regard to IL-4 serum level (5.10 pg/ml vs. 7.1 pg/ml). Analyzing the association between level of the examined cytokines and genotype polymorphisms -590 C/T for the IL-4 gene, -1082 A/G for the IL-10 gene and -1055 C/T for the IL-13 gene, we found a statistically higher IL-10 serum level among carriers of the G allele in the -1082 G/A IL-10 polymorphism both in AD and control groups. We did not find any significant differences between serum level of IL-4 and IL-13 in regard to genotype occurrence in examined polymorphisms: -590 C/T for the IL-4 gene and -1055 C/T for the IL-13 gene. The obtained results confirm the genetic background of IL-10 synthesis in the Polish population.

Skeletal muscle deiodinase type 2 regulation during illness in mice.

PubMed

Kwakkel, J; van Beeren, H C; Ackermans, M T; Platvoet-Ter Schiphorst, M C; Fliers, E; Wiersinga, W M; Boelen, A

2009-11-01

We have previously shown that skeletal muscle deiodinase type 2 (D2) mRNA (listed as Dio2 in MGI Database) is upregulated in an animal model of acute illness. However, human studies on the expression of muscle D2 during illness report conflicting data. Therefore, we evaluated the expression of skeletal muscle D2 and D2-regulating factors in two mouse models of illness that differ in timing and severity of illness: 1) turpentine-induced inflammation, and 2) Streptococcus pneumoniae infection. During turpentine-induced inflammation, D2 mRNA and activity increased compared to pair-fed controls, most prominently at day 1 and 2, whereas after S. pneumoniae infection D2 mRNA decreased. We evaluated the association of D2 expression with serum thyroid hormones, (de-)ubiquitinating enzymes ubiquitin-specific peptidase 33 and WD repeat and SOCS box-containing 1 (Wsb1), cytokine expression and activation of inflammatory pathways and cAMP pathway. During chronic inflammation the increased muscle D2 expression is associated with the activation of the cAMP pathway. The normalization of D2 5 days after turpentine injection coincides with increased Wsb1 and tumor necrosis factor alpha expression. Muscle interleukin-1beta (Il1b) expression correlated with decreased D2 mRNA expression after S. pneumoniae infection. In conclusion, muscle D2 expression is differentially regulated during illness, probably related to differences in the inflammatory response and type of pathology. D2 mRNA and activity increases in skeletal muscle during the acute phase of chronic inflammation compared to pair-fed controls probably due to activation of the cAMP pathway. In contrast, muscle D2 mRNA decreases 48 h after a severe bacterial infection, which is associated with local Il1b mRNA expression and might also be due to diminished food-intake.

The study of IL-1 beta, TNF-alpha, IL-6 gene expression and plasma levels on hemodialysis before and after dialyzer reuse.

PubMed

Qian, J; Yu, Z; Dai, H; Huang, P; Zhang, Q; Cheng, F; Chen, S

1997-07-01

To investigate the biocompatibility of dialyzer reuse. Twenty-two hemodialysis patients were randomized into cuprophan (CU, 7), polymethylmethacrylate (PMMA, 7) and polysulphone (PS, 8) membrane groups to observe IL-1 beta, TNF-alpha, IL-6 gene expression and their plasma levels by using themselves as control with enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Plasma levels of interlukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) were 14.07 +/- 3.32 pg/ml, 67.41 +/- 19.79 pg/ml, 83.67 +/- 40.34 pg/ml; 12.80 +/- 3.01 pg/ml, 49.65 +/- 9.75 pg/ml, 33.36 +/- 12.14 pg/ml and 14.41 +/- 3.16 pg/ml, 80.56 +/- 23.22 pg/ml, 48.14 +/- 16.01 pg/ml, respectively, after patients dialyzed with CU, PMMA and PS membranes. Plasma cytokine levels decreased after reuse compared with those before reuse in each group. But no significant difference was found between them (P > 0.05); the levels of IL-1 beta, TNF-alpha, IL-6 gene expression after reuse were 5.61 +/- 0.33, 2.11 +/- 0.12, 5.04 +/- 0.19%; 2.43 +/- 0.19, 1.29 +/- 0.11, 3.48 +/- 0.20% and 2.48 +/- 0.20, 1.24 +/- 0.11, 3.22 +/- 0.20% respectively by in situ hybridization, and 0.92 +/- 0.07, 0.63 +/- 0.05, 0.53 +/- 0.05; 0.61 +/- 0.06, 0.47 +/- 0.04, 0.37 +/- 0.03 and 0.59 +/- 0.05, 0.44 +/- 0.04, 0.38 +/- 0.03 by RT-PCR, respectively. After reuse there was significant decrease as compared with that before reuse (P < 0.001, P < 0.005 and P < 0.05, respectively). This suggested reprocessing dialyzer with formaldehyde reduced cytokine release and gene expression in peripheral blood mononuclear cells and enhanced dialyzer biocompatibility. It would be beneficial to reduce the dialysis cost and may reduce the complication related to a long term hemodialysis.

Chronically Ill Children in America: Background and Recommendations.

ERIC Educational Resources Information Center

Hobbs, Nicholas; And Others

The report examines chronic illness in children and considers issues and recommendations for change in public policies and programs affecting chronically ill children and their families. The background chapter notes the significance of the problem, reviews 11 diseases that are representative of the severe chronic illnesses of childhood: juvenile…

OM85-BV Induced the Productions of IL-1β, IL-6, and TNF-α via TLR4- and TLR2-Mediated ERK1/2/NF-κB Pathway in RAW264.7 Cells

PubMed Central

Luan, Hong; Zhang, Qian; Wang, Le; Wang, Chuanxiao; Zhang, Miao; Xu, Xiaoli; Zhou, Huan; Li, Xing'ai; Xu, Qing; He, Fan

2014-01-01

Broncho-Vaxom (OM85-BV) is an extract mixture from 8 strains of Gram+ and Gram− bacteria and plays an important role in anti-infection immune response by regulating macrophage activity and cytokine productions. However, the mechanism by which OM85-BV enhances the cytokine expression is still obscure. In this study, we evaluated the effects of OM85-BV on the productions of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in RAW264.7 murine macrophages. Exposure of RAW264.7 cells to 100 μg/mL OM85-BV upregulated the expression of IL-1β, IL-6, and TNF-α at the mRNA and protein levels in a time- and dose-dependent manner. In addition, OM85-BV induced extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor-kappa B (NF-κB) phosphorylation. Pretreatment with U0126 or Bay11-7082, respectively, could decrease IL-1β, IL-6, and TNF-α productions induced by OM85-BV. Application of Toll-like receptor (TLR) 4 or TLR2 small-interfering RNA (siRNA) into RAW264.7 cells could inhibit the productions of cytokines and ERK1/2 and NF-κB phosphorylation induced by OM85-BV. Consistent with this, downregulating either myeloid differentiation factor 88 (MyD88) or TRIF-related adaptor molecule (TRAM) gene with MyD88-siRNA or TRAM-siRNA separately could reduce the productions of cytokines and ERK1/2 and NF-κB phosphorylation induced by OM85-BV. Our study demonstrated that the productions of IL-1β, IL-6, and TNF-α induced by OM85-BV in RAW264.7 cells were through TLR4 and TLR2 signaling pathway-mediated activation of ERK1/2 and NF-κB. PMID:24605772

Occupational Emergency Medicine - Introduction

DTIC Science & Technology

2011-01-01

ril lo r the bu ’ eml ..’ rgen • ph i ia n in ea reh or a pra ti al guide ro occupa tional l1wLiicil1l’ in the emerg ’ncy der a n · menl. Occu pa...prol e llvc eq uip me n t ( I )PI~ d o C’ ~ Jlnt u s u il ll 0 cu r ill th L: ’m ergcl l (kp~ r1Ill" I1 I . Jil emL ’ rgell cy pll ysi Ian ll1il Y n

Cyclosporin A inhibits CD11a/CD18 adhesion molecules due to inhibition of TNFα and IL-1β levels in the mouse model of pleurisy induced by carrageenan

PubMed Central

Dalmarco, Eduardo Monguilhott; Medeiros, Yara Santos

2008-01-01

The mouse model of pleurisy induced by carrageenan is characterized by a significant enhancement of cell migration due to neutrophils 4 h after pleurisy induction. Forty-eight hours after pleurisy induction, a significant increase in cell migration due to mononuclear cells occurs. Recently, studies in our laboratory have demonstrated that cyclosporine A (CsA) inhibits leukocyte migration in the pleural cavity and lungs in the mouse model of pleurisy induced by carrageenan. In the present work we evaluated whether CsA was able to downregulate CD11a/CD18 adhesion molecule in the lungs, as well as TNFα and IL-1β levels in the fluid leakage of the pleural cavity in this model. Our results showed that CsA significantly decreased CD11a/CD18 in the lungs, as well as TNFα and IL-1β levels in the fluid leakage of the pleural cavity 4 h and 48 h after pleurisy induction. It is our hypothesis that the inhibitory effect elicited by CsA upon these adhesion molecules may be also be attributed to the downregulation of TNFα and IL-1β cytokines. PMID:19262158

Long-term outcome of patients with neurotic illness in general practice.

PubMed Central

Lloyd, K. R.; Jenkins, R.; Mann, A.

1996-01-01

OBJECTIVE--To determine the 11 year outcome of neurotic disorder in general practice. DESIGN--Cohort study over 11 years. SETTING--Two general practices in Warwickshire England. SUBJECTS--100 patients selected to be representative of those identified nationally by general practitioners as having neurotic disorders. MAIN OUTCOME MEASURES--Mortality, morbidity, and use of health services. RESULTS--At 11 years 87 subjects were traced. The 11 year standardised mortality ratio was 173 (95% confidence interval 164 to 200). 47 were cases on the general health questionnaire, 32 had a relapsing or chronic psychiatric course, and 49 a relapsing or chronic physical course. Treatment for psychiatric illness was mainly drugs. The mean number of consultations per year was 10.8 (median 8.7). A persistent psychiatric diagnosis at one year follow up was associated with high attendance ( > 12 visits a year for 11 years) at follow up after age, sex, and physical illness were adjusted for. Severity of psychiatric illness (general health questionnaire score) at outset predicted general health questionnaire score at 11 year follow up, course of psychiatric illness, and high consultation rate. CONCLUSION--These data support the view that a neurotic illness can become chronic and is associated with raised mortality from all causes and high use of services. Such patients need effective intervention, particularly those with a more severe illness who do not recover within one year. PMID:8664767

PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness.

PubMed

Chang, Kun; Qu, Yuanyuan; Dai, Bo; Zhao, Jian-Yuan; Gan, Hualei; Shi, Guohai; Zhu, Yiping; Shen, Yijun; Zhu, Yao; Zhang, Hailiang; Ye, Dingwei

2017-05-18

Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). The median PFS and OS for the whole cohort were 13.0 months (95% confidence interval [CI], 9.4-16.6 months) and 36.0 months (95% CI, 23.9-48.1 months), respectively. Our findings suggest that positive PD-L1 expression is indicative of worse clinical outcome in Xp11.2 RCC. Further studies are needed to explore the potential efficacy of targeting PD-L1 in Xp11.2 RCC.

GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering.

PubMed

Kahles, Florian; Meyer, Christina; Möllmann, Julia; Diebold, Sebastian; Findeisen, Hannes M; Lebherz, Corinna; Trautwein, Christian; Koch, Alexander; Tacke, Frank; Marx, Nikolaus; Lehrke, Michael

2014-10-01

Hypoglycemia and hyperglycemia are both predictors for adverse outcome in critically ill patients. Hyperinsulinemia is induced by inflammatory stimuli as a relevant mechanism for glucose lowering in the critically ill. The incretine hormone GLP-1 was currently found to be induced by endotoxin, leading to insulin secretion and glucose lowering under inflammatory conditions in mice. Here, we describe GLP-1 secretion to be increased by a variety of inflammatory stimuli, including endotoxin, interleukin-1β (IL-1β), and IL-6. Although abrogation of IL-1 signaling proved insufficient to prevent endotoxin-dependent GLP-1 induction, this was abolished in the absence of IL-6 in respective knockout animals. Hence, we found endotoxin-dependent GLP-1 secretion to be mediated by an inflammatory cascade, with IL-6 being necessary and sufficient for GLP-1 induction. Functionally, augmentation of the GLP-1 system by pharmacological inhibition of DPP-4 caused hyperinsulinemia, suppression of glucagon release, and glucose lowering under endotoxic conditions, whereas inhibition of the GLP-1 receptor led to the opposite effect. Furthermore, total GLP-1 plasma levels were profoundly increased in 155 critically ill patients presenting to the intensive care unit (ICU) in comparison with 134 healthy control subjects. In the ICU cohort, GLP-1 plasma levels correlated with markers of inflammation and disease severity. Consequently, GLP-1 provides a novel link between the immune system and the gut with strong relevance for metabolic regulation in context of inflammation. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Strikingly higher interleukin (IL)-1alpha, IL-1beta and soluble interleukin-1 receptor antagonist (sIL-1RA) but similar IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta and interferon IFN-gamma urine levels in healthy females compared to healthy males: protection against urinary tract injury?

PubMed

Sadeghi, M; Daniel, V; Naujokat, C; Weimer, R; Opelz, G

2005-11-01

The aim of this prospective study was to examine gender-related differences of cytokines in the plasma and urine of healthy individuals that might provide a clue concerning the lower rate of chronic renal diseases in females. Soluble interleukin-1 receptor antagonist (sIL-1RA), interleukin (IL)-1alpha, IL-1beta, IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta(2) and interferon (IFN)-gamma were determined using standard enzyme-linked immunosorbent assay (ELISA). Cytokine levels were determined in simultaneously obtained plasma and urine samples of 18 male and 28 female healthy members of our laboratory staff. Urine cytokine levels were studied three times at 1-month intervals. All individuals had a negative urine nitrite test and showed no symptoms of urinary tract infection (UTI). Plasma levels of all studied cytokines were similar in males and females (P = n.s.). However, females had significantly higher urine IL-1alpha (P < 0.0001; P < 0.0001; P < 0.0001) and sIL-1RA (P = 0.0001; P = 0.0003; P = 0.0002) than males at three and higher IL-1beta at one of the three investigations (P = 0.098; P = 0.003; P = 0.073). Urine levels of the other cytokines were similar in males and females. Higher urine levels of IL-1alpha, IL-1beta and sIL-1RA in females may result from stimulation of cells in the urinary tract. Increased sIL-1RA might block T lymphocyte activation. The elevated cytokines may play a role in the protection of the female urinary tract from certain renal diseases, such as pyelonephritis and other inflammatory and sclerotic kidney diseases.

Identification of interleukin-8 converting enzyme as cathepsin L.

PubMed

Ohashi, Kensaku; Naruto, Masanobu; Nakaki, Toshio; Sano, Emiko

2003-06-26

IL-8 is produced by various cells, and the NH(2)-terminal amino acid sequence of IL-8 displays heterogeneity among cell types. The mature form of IL-8 has 72 amino acids (72IL-8), while a precursor form (77IL-8) of IL-8 has five additional amino acids to the 72IL-8 NH(2)-terminal. However, it has been unclear how IL-8 is processed to yield the mature form. In this study, converting enzyme was purified as a single 31-kDa band on silver-stained polyacrylamide gel from 160 l of cultured fibroblast supernatant by sequential chromatography. NH(2)-terminal amino acid sequence analysis revealed a sequence, EAPRSVDWRE, which was identified as a partial sequence of cathepsin L. Polyclonal antibodies raised against cathepsin L recognized the purified converting enzyme on Western blot. Moreover, human hepatic cathepsin L cleaved 77IL-8 between Arg(5) and Ser(6), which is the same cleavage site as the putative converting enzyme, resulting in 72IL-8 formation. These data indicate that the converting enzyme of the partially purified fraction of the human fibroblast culture supernatant was cathepsin L. Furthermore, 72IL-8 was sevenfold more potent than 77IL-8 in a neutrophil chemotaxis assay. These results show that cathepsin L is secreted from human fibroblasts in response to external stimuli and plays an important role in IL-8 processing in inflammatory sites.

Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis.

PubMed

Ishibashi, Naoya; Watanabe, Tatsuaki; Kanehira, Masahiko; Watanabe, Yui; Hoshikawa, Yasushi; Notsuda, Hirotsugu; Noda, Masafumi; Sakurada, Akira; Ohkouchi, Shinya; Kondo, Takashi; Okada, Yoshinori

2018-03-15

Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis

PubMed Central

Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2007-01-01

Targeted Interleukin (IL)-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild type (WT) littermates (n=127) were subjected to cecal ligation and puncture with a 27-gauge needle. Seven-day survival was 45% in transgenic animals and 30% in WT animals (p≤0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals, regardless of whether they expressed the transgene. Local parameters of injury including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines and stimulated cytokines from intraepithelial lymphocytes were similar between transgenic and wildtype mice. However, in stimulated splenocytes, pro-inflammatory cytokines MCP-1 (189 ± 43 pg/ml vs. 40 ± 8 pg/ml) and IL-6 (116 ± 28 pg/ml vs. 34 ± 9 pg/ml) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (p<0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the two groups as were circulating LPS levels. Transgenic mice also had lower white blood cell counts, associated with lower absolute neutrophil counts (0.5 ± 0.1 103/mm3 vs. 1.0 ± 0.2 103/mm3, p<0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage. PMID:17998890

Association between vitamin D levels and inflammatory activity in brain death: A prospective study.

PubMed

Custódio, Geisiane; Schwarz, Patrícia; Crispim, Daisy; Moraes, Rafael B; Czepielewski, Mauro; Leitão, Cristiane B; Rech, Tatiana H

2018-06-01

Vitamin D insufficiency is linked to several common inflammatory disorders. Brain death (BD) causes a massive catecholamine release, leading to intense inflammatory activity. We aimed to evaluate vitamin D serum levels in brain-dead individuals in comparison to critically ill patients without BD to assess the correlation between vitamin D and cytokine levels. Sixteen brain-dead patients and 32 critically ill controls were prospectively enrolled. Blood samples from 25 brain-dead patients from a previous study were also used for vitamin D quantification. Plasma TNF, IL-1β, IL-6, IL-8, IL-10, IFN-γ and serum vitamin D levels were compared using Student's t-test or one-way ANOVA. Spearman's test was used to assess the correlation between vitamin D and cytokine levels. Mean vitamin D levels were 16.4 ± 7.9 ng/mL, with 52 patients (71.2%) classified as vitamin D deficient (serum levels < 20 ng/mL). Vitamin D levels were similar in 41 brain-dead patients as compared to control subjects (15.6 ± 6.9 ng/mL vs 17.4 ± 9.0 ng/mL; p = 0.383). Moderate direct correlations were observed between vitamin D and IL-8, IL-10, and IFN-γ in the prospective group of 16 brain-dead patients (IL-8: r = 0.5, p = 0.049; IL-10 r = 0.67, p = 0.005; IFN-γ r = 0.6, p = 0.015). Vitamin D was inversely correlated with IL-6 (r = -0.36, p = 0.044) in critically ill controls. Vitamin D serum levels were similarly low in brain-dead and critically ill patients. In brain-dead patients, vitamin D serum levels correlated with plasma IL-8, IL-10 and IFN-γ. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of high dose tumescent local anaesthesia with prilocaine on systemic interleukin (IL)-6, IL-8 and tumour necrosis factor-α.

PubMed

Schmittner, M D; Faulhaber, J; Kemler, B; Koenen, W; Thumfart, J O; Weiss, C; Neumaier, M; Beck, G C

2010-12-01

Tumescent local anaesthesia (TLA) with high prilocaine doses leads to formation of methemoglobin (MHb) which is known to be a potent activator of pro-inflammatory endothelial cell response in vitro. As TLA is widely used for large dermatological resections, the aim of this study was to investigate the effects of high prilocaine doses on the systemic inflammatory response in vivo and its clinical relevance. This prospective study examines the influence of MHb on serum interleukin (IL)-6, IL-8 and tumour necrosis tumour necrosis (TNF)-α levels up to 72 h after application of TLA with prilocaine in doses higher than 600 mg. A total of 30 patients received prilocaine in a median dose of 1500 mg (range: 880-4160 mg) for large resections. Peak prilocaine serum concentration was reached 4 h (0.72 ± 0.07 μg/mL), the maximum concentration of MHb (7.43 ± 0.87%) and IL-6 (28.4 ± 4.1 U/L) 12 h after TLA application. TNF-α and IL-8 release were not found significantly increased. Three patients developed MHb concentrations >15%. This clinical study shows for the first time that a high prilocaine serum concentration leads in vivo to elevated systemic levels of IL-6 but not of IL-8 and TNF-α because of initial high MHb levels. Because of possible and unpredictable high MHb concentrations, TLA should only be performed with prilocaine in doses of 2.5 mg/kg. In general, new solutions of TLA are necessary to achieve adequate anaesthesia for large dermatological resections to decrease the risk of methemoglobinaemia. © 2010 The Authors. Journal compilation © 2010 European Academy of Dermatology and Venereology.

77 FR 52292 - Radio Broadcasting Services; Greenup, IL

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

...] Radio Broadcasting Services; Greenup, IL AGENCY: Federal Communications Commission. ACTION: Proposed...) southwest of the community. The reference coordinates are 39-12-38 NL and 88-11- 15 WL. [[Page 52293

IL-17 Promotes Angiogenic Factors IL-6, IL-8, and Vegf Production via Stat1 in Lung Adenocarcinoma.

PubMed

Huang, Qi; Duan, Limin; Qian, Xin; Fan, Jinshuo; Lv, Zhilei; Zhang, Xiuxiu; Han, Jieli; Wu, Feng; Guo, Mengfei; Hu, Guorong; Du, Jiao; Chen, Caiyun; Jin, Yang

2016-11-07

Inflammation and angiogenesis are two hallmarks of carcinoma. The proinflammatory cytokine interleukin-17 (IL-17) facilitates angiogenesis in lung cancer; however, the underlying mechanism is not fully understood. In this study, tumour microvessel density (MVD) was positively associated with IL-17, interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial cell growth factor (VEGF) expression in human lung adenocarcinoma tissues, and it was increased in tumour tissues of A549-IL-17 cell-bearing nude mice. Importantly, positive correlations were also detected between IL-17 expression and IL-6, IL-8 and VEGF expression in human lung adenocarcinoma tissues. Furthermore, IL-6, IL-8 and VEGF production, as well as STAT1 phosphorylation, were increased in tumour tissues of A549-IL-17 cell-bearing nude mice in vivo and in A549 and H292 cells following IL-17 stimulation in vitro. In addition, STAT1 knockdown using an inhibitor and siRNA attenuated the IL-17-mediated increases in IL-6, IL-8 and VEGF expression in A549 and H292 cells. In conclusion, IL-17 may promote the production of the angiogenic inducers IL-6, IL-8 and VEGF via STAT1 signalling in lung adenocarcinoma.

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place. Part 11 (Hilton Systems Inc -International Industries Inc)

DTIC Science & Technology

1990-01-01

A11 10 m 4(1 CI (00 10 <D 0 1(0 (4 -1 -*It j-I -ti j 1 -114 -14 1N N r > KfC i i-I - of ’D I <( m it 4 44 LAO<< U)U IL- C LAO L𔃻 ~ I- Ai>> tor)> LNMMM...4 if Z InIn In in n toIn tr onIn In Z.10- 01 o( c > ) In In n InfLn InL In I n 20 C ZIn InfIn Z In 11. if-c I (0-4 11Ir nV no U1(1() on C )() 0 I a1

Developing a multi-component immune model for evaluating the risk of respiratory illness in athletes.

PubMed

Gleeson, Maree; Pyne, David B; Elkington, Lisa J; Hall, Sharron T; Attia, John R; Oldmeadow, Christopher; Wood, Lisa G; Callister, Robin

2017-01-01

Clinical and laboratory identification of the underlying risk of respiratory illness in athletes has proved problematic. The aim of this study was to determine whether clinical data, combined with immune responses to standardised exercise protocols and genetic cytokine polymorphism status, could identify the risk of respiratory illness (symptoms) in a cohort of highly-trained athletes. Male endurance athletes (n=16; VO2max 66.5 ± 5.1 mL.kg-1.min-1) underwent a clinical evaluation of known risk factors by a physician and comprehensive laboratory analysis of immune responses both at rest and after two cycling ergometer tests: 60 min at 65% VO2max (LONG); and 6 x 3 min intervals at 90% VO2max (INTENSE). Blood tests were performed to determine Epstein Barr virus (EBV) status and DNA was genotyped for a panel of cytokine gene polymorphisms. Saliva was collected for measurement of IgA and detection of EBV DNA. Athletes were then followed for 9 months for self-reported episodes of respiratory illness, with confirmation of the underlying cause by a sports physician. There were no associations with risk of respiratory illness identified for any parameter assessed in the clinical evaluations. The laboratory parameters associated with an increased risk of respiratory illnesses in highly-trained athletes were cytokine gene polymorphisms for the high expression of IL-6 and IFN-ɣ; expression of EBV-DNA in saliva; and low levels of salivary IgA concentration. A genetic risk score was developed for the cumulative number of minor alleles for the cytokines evaluated. Athletes prone to recurrent respiratory illness were more likely to have immune disturbances that allow viral reactivation, and a genetic predisposition to pro-inflammatory cytokine responses to intense exercise. Copyright © 2016 International Society of Exercise and Immunology. All rights reserved.

Visual Acuity and the Balance between Receptor Density and Ganglion Cell Receptive Field Overlap.

DTIC Science & Technology

1980-07-01

Physiol. 229:719-731. Cleland, B . G., Dubin, M. W. and Levick , W. R. (1971) Sustained and transient neurones in the cat’s retina and lateral...NOOOIQ.79C-0370 NLASSIFIED IA. EEEEEEEEEEinnuunuuuuuu ’mLuuuu~ 4,0 111 12. 11111IL25 1.4I 111111.6 MICROCOPY RESOLUTION TEST CHART LEVEt 9 70 b *tm...1970; Burke and Hayhow, 1968; Barlow and Levick , 1969). As far as they affect the ganglion cell, these sources of noise are equivalent so they have been

Illness perception in patients with androgenetic alopecia and alopecia areata in China.

PubMed

Yu, Nan-Lan; Tan, Huan; Song, Zhi-Qiang; Yang, Xi-Chuan

2016-07-01

The aim of the present study was to provide more information on the role of illness perception in patients with androgenetic alopecia (AGA) and those with alopecia areata (AA), and to further investigate the relationship of illness perception with psychological disorders and dermatological QoL. The study included 342 patients who were diagnosed with AGA (n=212) or AA (n=130) for the first time at our institution between October 2013 and December 2014. All patients were surveyed before clinical examination by several questionnaires including the Brief Illness Perception, Self-rating Depression Scale, Self-rating Anxiety Scale, and Dermatology Life Quality Index (DLQI). In the AGA patients, the illness perception and QoL were low, whereas the prevalence of clinical depression and anxiety was higher compared to the AA patients. Illness perception was associated with psychological distress and low QoL in both groups, and some illness perception dimensions were found to be significant predictors of the DLQI scores. Illness perception plays an important role in AGA and AA patients, and is associated with psychological distress and low QoL. The identification of critical components of illness perception in alopecia patients could help to understand alopecia specificities, to design consultations and interventions according to the perception, and to improve physical and mental outcomes as well as QoL in alopecia patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma.

PubMed

Agrawal, Swati; Townley, Robert G

2014-02-01

Asthma markedly diminishes quality of life due to limited activity, absences from work or school and hospitalizations. Patients with severe asthma which are not controlled despite taking effective therapy are most in need of new treatment approaches. IL-13 was demonstrated as 'central mediator of allergic asthma'. IL-13 has been implicated in the pathogenesis of asthma, idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial biopsy samples remain elevated in severe asthma despite the use of inhaled and systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid resistance. Periostin enhances profibrotic TGF-β signaling in subepithelial fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to secrete periostin. Periostin may be a biomarker for Th2 induced airway inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab improved lung function in asthmatics who were symptomatic despite treatment with long acting beta agonist and inhaled corticosteroids and provided benefit in the treatment of severe uncontrolled asthma. Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.

77 FR 47918 - Chicago Central and Pacific Railroad Company-Abandonment Exemption-in Cook County, IL

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

... Central and Pacific Railroad Company--Abandonment Exemption--in Cook County, IL Chicago Central and... North Riverside, Cook County, Ill. The line traverses United States Postal Service Zip Codes 60546 and... system. A copy of any petition filed with the Board should be sent to CCP's representative: Thomas J...

Process and Energy Optimization Assessment, Rock Island Arsenal, IL

DTIC Science & Technology

2004-09-01

Approved for public release; distribution is unlimited. ER D C /C ER L TR -0 4- 17 Process and Energy Optimization Assessment Rock Island... Optimization Assessment: Rock Island Arsenal, IL Mike C.J. Lin, Alexander M. Zhivov, and Veera M. Boddu, Construction Engineering Research...and Energy Optimization Assessment (PEOA) was conducted at Rock Island Arsenal (RIA), IL to identify process, energy, and environmental opportunities

Acute illnesses associated with exposure to fipronil--surveillance data from 11 states in the United States, 2001-2007.

PubMed

Lee, Soo-Jeong; Mulay, Prakash; Diebolt-Brown, Brienne; Lackovic, Michelle J; Mehler, Louise N; Beckman, John; Waltz, Justin; Prado, Joanne B; Mitchell, Yvette A; Higgins, Sheila A; Schwartz, Abby; Calvert, Geoffrey M

2010-08-01

Fipronil is a broad-spectrum phenylpyrazole insecticide widely used to control residential pests and is also commonly used for flea and tick treatment on pets. It is a relatively new insecticide and few human toxicity data exist on fipronil. This paper describes the magnitude and characteristics of acute illnesses associated with fipronil exposure. Illness cases associated with exposure to fipronil-containing products from 2001 to 2007 were identified from the Sentinel Event Notification System for Occupational Risks (SENSOR)-Pesticides Program and the California Department of Pesticide Regulation. A total of 103 cases were identified in 11 states. Annual case counts increased from 5 in 2001 to 30 in 2007. Of the cases, 55% were female, the median age was 37 years, and 11% were <15 years old. The majority (76%) had exposure in a private residence, 37% involved the use of pet-care products, and 26% had work-related exposures. Most cases (89%) had mild, temporary health effects. Neurological symptoms (50%) such as headache, dizziness, and paresthesia were the most common, followed by ocular (44%), gastrointestinal (28%), respiratory (27%), and dermal (21%) symptoms/signs. Exposures usually occurred from inadvertent spray/splash/spill of products or inadequate ventilation of the treated area before re-entry. Our findings indicate that exposure to fipronil can pose a risk for mild, temporary health effects in various body systems. Precautionary actions should be reinforced to prevent fipronil exposure to product users.

Hypophosphatemia in critically ill patients.

PubMed

Suzuki, Satoshi; Egi, Moritoki; Schneider, Antoine G; Bellomo, Rinaldo; Hart, Graeme K; Hegarty, Colin

2013-08-01

The aim of this study was to assess the association of phosphate concentration with key clinical outcomes in a heterogeneous cohort of critically ill patients. This was a retrospective observational study at a general intensive care unit (ICU) of an Australian university teaching hospital enrolling 2730 adult critically ill patients. We studied 10504 phosphate measurements with a mean value of 1.17 mmol/L (measurements every 28.8 hours on average). Hyperphosphatemia (inorganic phosphate [iP] concentration > 1.4 mmol/L) occurred in 45% and hypophosphatemia (iP ≤ 0.6 mmol/L) in 20%. Among patients without any episodes of hyperphosphatemia, patients with at least 1 episode of hypophosphatemia had a higher ICU mortality than those without hypophosphatemia (P = .004). In addition, ICU nonsurvivors had lower minimum phosphate concentrations than did survivors (P = .009). Similar results were seen for hospital mortality. However, on multivariable logistic regression analysis, hypophosphatemia was not independently associated with ICU mortality (adjusted odds ratio, 0.86 [95% confidence interval, 0.66-1.10]; P = .24) and hospital mortality (odds ratio, 0.89 [0.73-1.07]; P = .21). Even when different cutoff points were used for hypophosphatemia (iP ≤ 0.5, 0.4, 0.3, or 0.2 mmol/L), hypophosphatemia was not an independent risk factor for ICU and hospital morality. In addition, timing of onset and duration of hypophosphatemia were not independent risk factor for ICU and hospital mortality. Hypophosphatemia behaves like a general marker of illness severity and not as an independent predictor of ICU or in-hospital mortality in critically ill patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Study to Determine the Impact of Aircrew Anthropometry on Airframe Configuration.

DTIC Science & Technology

1976-10-31

Fie t0) PILO PEDAL 1F.A STR ~fAW1 I Il. VD 2. LEAAN II)W HANYJ(ON MAX 817E FOOTWFAII. TOIIIOMKM Sitfi4I FORWARDN) Nou v ims-ritAIT% InhITKIN WiT11 lILL...designed as specified in Figure 18. 7.4.3 Xaw Control. Pedal munge - Forward and aft limits of yaw controls shall be as defined in Figures 16 and 17. 8

National Dam Safety Program. Structure F-2 (MO 20513), Verdigris - Neosho River Basin, Newton County, Missouri. Phase I Inspection Report.

DTIC Science & Technology

1980-08-01

AXIAL- INITIAL [00 NS CL 13~ rf START DEGOF SATI END CONS;0LI- PRINCIPIAL s T. -s STRAIN AT PU n I DIE~)0.1 AT S f A RT OF IA WON STES I ru Pcf cO DA...SAM.PLE. LUCAII’N FIELD SMk -11 N,) (1711H CLOLOCIZ Cii... 3~ ( i_ . __ _ _ _ __ _ _ TNE I LNETU)D AT API’lOV’U) V~ CA CLASSIFICATION Il!LL ill/P1

Electromagnetic Interference Tests

DTIC Science & Technology

1994-05-31

for Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Fields (300 kHz - 100 GHz), American National Standards Institute...Respect to Human Exposure to Radio Frequency Electromagnetic Fields (300 kHz - 100 GHz), American National Standards Institute, C95.1-1982, 30 July 1980...II il~l I!I 11 lll i 13. ABSTkACT (Waxlrnun 200woruh) This TOP is a general guideline for electromagnetic interference testing of electronic

Four cases of investigational therapy with interleukin-11 against acute myocardial infarction.

PubMed

Nakagawa, Masashi; Owada, Yasuko; Izumi, Yasukatsu; Nonin, Shinichi; Sugioka, Kenichi; Nakatani, Daisaku; Iwata, Shinichi; Mizutani, Kazuki; Nishimura, Satoshi; Ito, Asahiro; Fujita, Suwako; Daimon, Takashi; Sawa, Yoshiki; Asakura, Masanori; Maeda, Makiko; Fujio, Yasushi; Yoshiyama, Minoru

2016-09-01

We describe four cases of the patients with ST-elevation myocardial infarction (STEMI) that were treated with interleukin-11 (IL-11), a cardioprotective cytokine. Recombinant human IL-11 (rhIL-11), was intravenously administered to two cases at low dose (6 µg/kg) and to two at high dose (25 µg/kg). The cytokine administration started just after the coronary occlusion was confirmed by coronary angiography (CAG), taking 3 h. Following CAG, percutaneous coronary intervention (PCI) was performed as a standard therapy. No serious adverse drug reactions were observed. All the cases left the hospital without the symptom of heart failure. We discuss the possibility of the clinical use of rhIL-11 as an adjunct therapy to PCI for the STEMI patients.

Upper Atmosphere Research Report Number 5

DTIC Science & Technology

1948-06-17

instrument was recovered, however, and in good condition. TRAJECTORY ALTITUDE AND VELOCITY Vb TIME 1Q170 T- 170 ISO ----- -- d *--- -------- 150 1600-A...8217aa- 6- 2~~D v Y 0 0 , 1 3$%-3p’P 0 Fel UL !UAT .21 ,’S P I1L11*1111-z Fe -II RI a D- 0C Si I3e 3P- 4s3P0 02400 2500 2600 27000 WAVELENGTH...tototot- to 4 L (4 ~~~~4 toý to ).- IDt 0 4 mo ao 0--0)o- cot i0 t CU1 Ci) M4 ISo &a0c 0c nU n s U4C - ~ r e 4.o..4 -W--I~4 w-t4 M..4(4.4 (4(4l C Mt

IL-17 Contributes to Cell-Mediated Defense against Pulmonary Yersinia pestis Infection1

PubMed Central

Lin, Jr-Shiuan; Kummer, Lawrence W.; Szaba, Frank M.; Smiley, Stephen T.

2010-01-01

Pneumonic plague is one of the world’s most deadly infectious diseases. The causative bacterium, Yersinia pestis, has the potential to be exploited as a biological weapon and no vaccine is available. Vaccinating B cell-deficient mice with D27-pLpxL, a live attenuated Y. pestis strain, induces cell-mediated protection against lethal pulmonary Y. pestis challenge. Here we demonstrate that prime/boost vaccination with D27-pLpxL confers better protection than prime-only vaccination. The improved survival does not result from enhanced bacterial clearance, but is associated with increased levels of IL-17 mRNA and protein in the lungs of challenged mice. The boost also increases pulmonary numbers of IL-17-producing CD4 T cells. Interestingly, the vast majority of these cells simultaneously produce canonical type 1 and type 17 cytokines; most produce IL-17 and TNFα, and many produce IL-17, TNFα and IFNγ. Neutralizing IL-17 counteracts the improved survival associated with prime/boost vaccination without significantly impacting bacterial burden. Thus, IL-17 appears to mediate the enhanced protection conferred by booster immunization. Although neutralizing IL-17 significantly reduces neutrophil recruitment to the lungs of mice challenged with Y. pestis, this impact is equally evident in mice that receive one or two immunizations with D27-pLpxL, suggesting it cannot suffice to account for the improved survival that results from booster immunization. We conclude that IL-17 plays a yet to be identified role in host defense that enhances protection against pulmonary Y. pestis challenge, and we suggest that pneumonic plague vaccines should aim to induce mixed type 1 and type 17 cellular responses. PMID:21172869

Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines.

PubMed

Gelaleti, Gabriela Bottaro; Borin, Thaiz Ferraz; Maschio-Signorini, Larissa Bazela; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Calvinho, Guilherme Berto; Facchini, Mariana Castilho; Viloria-Petit, Alicia M; de Campos Zuccari, Debora Aparecida Pires

2017-08-15

Mammary tumorigenesis can be modulated by melatonin, which has oncostatic action mediated by multiple mechanisms, including the inhibition of the activity of transcription factors such as NF-κB and modulation of interleukins (ILs) expression. IL-25 is an active cytokine that induces apoptosis in tumor cells due to differential expression of its receptor (IL-17RB). IL-17B competes with IL-25 for binding to IL-17RB in tumor cells, promoting tumorigenesis. This study purpose is to address the possibility of engaging IL-25/IL-17RB signaling to enhance the effect of melatonin on breast cancer cells. Breast cancer cell lines were cultured monolayers and 3D structures and treated with melatonin, IL-25, siIL-17B, each alone or in combination. Cell viability, gene and protein expression of caspase-3, cleaved caspase-3 and VEGF-A were performed by qPCR and immunofluorescence. In addition, an apoptosis membrane array was performed in metastatic cells. Treatments with melatonin and IL-25 significantly reduced tumor cells viability at 1mM and 1ng/mL, respectively, but did not alter cell viability of a non-tumorigenic epithelial cell line (MCF-10A). All treatments, alone and combined, significantly increased cleaved caspase-3 in tumor cells grown as monolayers and 3D structures (p<0.05). Semi-quantitative analysis of apoptosis pathway proteins showed an increase of CYTO-C, DR6, IGFBP-3, IGFBP-5, IGFPB-6, IGF-1, IGF-1R, Livin, P21, P53, TNFRII, XIAP and hTRA proteins and reduction of caspase-3 (p<0.05) after melatonin treatment. All treatments reduced VEGF-A protein expression in tumor cells (p<0.05). Our results suggest therapeutic potential, with oncostatic effectiveness, pro-apoptotic and anti-angiogenic properties for melatonin and IL-25-driven signaling in breast cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhanced Expression of IL-18 and IL-18BP in Plasma of Patients with Eczema: Altered Expression of IL-18BP and IL-18 Receptor on Mast Cells.

PubMed

Hu, Yalin; Wang, Junling; Zhang, Huiyun; Xie, Hua; Song, Weiwei; Jiang, Qijun; Zhao, Nan; He, Shaoheng

2017-01-01

IL-18 has been found to be associated with eczema. However, little is known of the role of IL-18 binding protein (BP) and IL-18 receptor (R) in eczema. We therefore investigated the expression of IL-18, IL-18BP, and IL-18R on mast cells by using flow cytometry analysis and mouse eczema model. The results showed that plasma free IL-18 and free IL-18BP levels in eczema patients were higher than those in healthy controls. IL-18 provoked up to 3.1-fold increase in skin mast cells. IL-18 induced also an increase in IL-18BP+ mast cells, but a reduction of IL-18R+ mast cells in mouse eczema skin. It was found that house dust mite allergen Der p1 and egg allergen OVA induced upregulation of the expression of IL-18, IL-18BP, and IL-18R mRNAs in HMC-1 cells following 2 and 16 h incubation. In conclusion, correlation of IL-18 and IL-18BP in eczema plasma suggests an important balance between IL-18 and IL-18BP in eczema. The decrease in molar concentration ratio of plasma IL-18BP/IL-18 and allergen-induced upregulated expression of IL-18 and IL-18R in skin mast cells of the patients with eczema suggests that anti-IL-18 including IL-18BP therapy may be useful for the treatment of eczema.

Enhanced Expression of IL-18 and IL-18BP in Plasma of Patients with Eczema: Altered Expression of IL-18BP and IL-18 Receptor on Mast Cells

PubMed Central

2017-01-01

IL-18 has been found to be associated with eczema. However, little is known of the role of IL-18 binding protein (BP) and IL-18 receptor (R) in eczema. We therefore investigated the expression of IL-18, IL-18BP, and IL-18R on mast cells by using flow cytometry analysis and mouse eczema model. The results showed that plasma free IL-18 and free IL-18BP levels in eczema patients were higher than those in healthy controls. IL-18 provoked up to 3.1-fold increase in skin mast cells. IL-18 induced also an increase in IL-18BP+ mast cells, but a reduction of IL-18R+ mast cells in mouse eczema skin. It was found that house dust mite allergen Der p1 and egg allergen OVA induced upregulation of the expression of IL-18, IL-18BP, and IL-18R mRNAs in HMC-1 cells following 2 and 16 h incubation. In conclusion, correlation of IL-18 and IL-18BP in eczema plasma suggests an important balance between IL-18 and IL-18BP in eczema. The decrease in molar concentration ratio of plasma IL-18BP/IL-18 and allergen-induced upregulated expression of IL-18 and IL-18R in skin mast cells of the patients with eczema suggests that anti-IL-18 including IL-18BP therapy may be useful for the treatment of eczema. PMID:28839348

Chemokine CXCL11 links microbial stimuli to intestinal inflammation

PubMed Central

Liu, Z; Chen, X; Wang, X; Chen, X; Song, C-H; Du, Y; Su, J; Yaseen, S A; Yang, P-C

2011-01-01

Interleukin (IL)-17 plays an important role in the pathogenesis in a number of immune inflammatory disorders. This study aims to investigate the mechanism by which microbial product flagellin is involved in the development of T helper type (Th)17 cells. Serum levels of IL-17 and CXCL9-11 in patients with ulcerative colitis (UC) were evaluated. The source and mechanism of CXC11 release in intestinal mucosa were examined with colonic biopsies from UC patients and a colitis mouse model. The role of flagellin in the development of Th17 cells was studied with a cell co-culture system. High serum levels of CXCL11 and IL-17 were observed in UC. Flagellin could induce the production of CXCL11 in CD14+ cells that facilitated the development of Th17 cells. In a skewed Th1 response environment flagellin induces intestinal inflammation, with IL-17 expression predominant. CXCR3/CXCL11 pathway is involved in microbial product flagellin-induced intestinal inflammation in which the Th17 response plays an important role. PMID:21438871