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IL-6 Expression (il-6 + expression)
Selected AbstractsExpression of inflammatory molecules and associations with BMI in childrenEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2010George V. Z. Dedoussis Eur J Clin Invest 2010; 40 (5): 388,392 Abstract Background, Adipose tissue secrets several adipokines that have been proposed to be enrolled in many inflammatory pathways. Our aim was to investigate the adipokine expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) in children. Materials and methods, Thirty-one (17 males and 14 females) healthy children aged 10·9 ± 1·8 years with a body mass index (BMI) of 19·3 ± 3·5 kg m,2 were enrolled. Adipokines (TNF-alpha, IL-6 and leptin) gene expression was quantified by real-time quantitative PCR in adipose tissue and PBMCs from the same children. Their serum levels were also measured. Results, BMI was positively correlated with leptin gene expression in adipose tissue and with leptin serum levels (, = 0·476, P = 0·006 and , = 0·576, P = 0·003 respectively). Leptin's serum levels were positively correlated with leptin gene expression in adipose tissue (, = 0·462, P = 0·02). Adipose tissue gene expression of leptin and TNF-alpha and serum leptin and TNF-alpha serum levels were positively correlated (, = 0·752, P < 0·001, , = 0·311 and P = 0·015 respectively). In PBMCs, a positive correlation between TNF-alpha and IL-6 expression was found (, = 0·526, P = 0·042). Conclusion, We demonstrated powerful correlations of adipokines gene expression in adipose tissue and PBMCs in children, underlying that these molecules share common pathways related to childhood obesity. [source] ME3738 protects from concanavalin,A-induced liver failure via an IL-6-dependent mechanismEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2003Christian Klein Abstract ME3738 is a new compound that attenuates liver disease in several models of acute and chronic liver inflammation. We used the concanavalin,A (Con,A) model to elucidate the molecular mechanismsof ME3738 to block liver cell damage. Pretreatment of BALB/c mice with ME3738 prior to Con,A injection resulted in a significant reduction in liver injury. The protective effect of ME3738 prior to Con,A injection was associated with a reduction in IL-6 serum levels and NF-,B DNA binding in liver nuclear extracts. However, STAT3 DNA binding was induced via ME3738 prior to Con,A injection. Further analysis showed that ME3738 induces IL-6 serum levels and activates STAT3 DNA binding and target gene transcription. The relevance of this finding was assessed in IL-6,/, mice. Inthese animals, ME3738 induced no increase in IL-6 serum expression, and activation of IL-6-dependent pathways was not found. In addition, ME3738 did not protect IL-6,/, animals from Con,A-induced liver failure, while IL-6 injection was still effective. Therefore, we demonstrate that ME3738 triggers IL-6 expression, which activates pathways that are relevant to protect from Con,A-induced liver failure. [source] Interferon-, synergistically enhances induction of interleukin-6 by double stranded RNA in HeLa cellsFEBS JOURNAL, Issue 9 2000Jennifer L. Harcourt Double stranded RNA (dsRNA), an intermediate that is common during viral infection, directly induces much higher levels of expression of interleukin-6 (IL-6) mRNA than does the cytokine IL-1,. Interferon , (IFN,) by itself does not induce expression of IL-6; nonetheless, IFN, pretreatment dramatically enhances IL-6 induction by dsRNA but not by IL-1,. Mutation of either the activating transcription factor/cyclic AMP response element binding protein (ATF/CREB) or the NF-IL-6 binding element within the IL-6 promoter eliminates most responsiveness of CAT reporter constructs to either dsRNA or to IL-1,. IFN, pretreatment partially restores responsiveness to dsRNA but not to IL-1, when either the ATF/CREB site or the NF-IL-6 site is mutated, but at least one of these sites must be intact for responsiveness to be restored. Mutation of the ,B binding site in the IL-6 promoter eliminates responsiveness to either IL-1, or to dsRNA, and pretreatment with IFN, does not restore any responsiveness. Incubation with dsRNA leads to a decrease in protein translation, especially in cells that have been pretreated with IFN,. Nonetheless, IFN, pretreatment followed by dsRNA leads to very high IL-6 protein levels. These studies demonstrate that major differences exist in the induction of IL-6 at both the mRNA and protein levels by dsRNA compared to cytokines and that IFN, pretreatment selectively enhances IL-6 induction by dsRNA but not by IL-1,. The high levels of IL-6 expression that result when cells encounter class I IFN prior to dsRNA suggest a mechanism for a heightened host response to viral infection with heightened production of this pleotropic cytokine. [source] Activation of the complement system in human nonalcoholic fatty liver disease,HEPATOLOGY, Issue 6 2009Sander S. Rensen Activation of the innate immune system plays a major role in nonalcoholic fatty liver disease (NAFLD). The complement system is an important component of innate immunity that recognizes danger signals such as tissue injury. We aimed to determine whether activation of the complement system occurs in NAFLD, to identify initiating pathways, and to assess the relation between complement activation, NAFLD severity, apoptosis, and inflammatory parameters. Liver biopsies of 43 obese subjects with various degrees of NAFLD and of 10 healthy controls were analyzed for deposition of complement factors C1q, mannose-binding lectin (MBL), C4d, activated C3, and membrane attack complex (MAC)-associated C9. Furthermore, hepatic neutrophil infiltration, apoptosis, and pro-inflammatory cytokine expression were quantified. Whereas complement activation was undetectable in the liver of healthy subjects, 74% of the NAFLD patients showed hepatic deposition of activated C3 and C4d. C1q as well as MBL accumulation was found in most activated C3-positive patients. Strikingly, 50% of activated C3-positive patients also displayed MAC-associated C9 deposition. Deposition of complement factors was predominantly seen around hepatocytes with macrovesicular steatosis. Subjects showing accumulation of activated C3 displayed increased numbers of apoptotic cells. Importantly, hepatic neutrophil infiltration as well as interleukin (IL)-8 and IL-6 expression was significantly higher in patients showing activated C3 deposition, whereas patients with C9 deposition additionally had increased IL-1, expression. Moreover, nonalcoholic steatohepatitis (NASH) was more prevalent in patients showing hepatic C9 or activated C3 deposition. Conclusion: There is widespread activation of the complement system in NAFLD, which is associated with disease severity. This may have important implications for the pathogenesis and progression of NAFLD given the function of complement factors in clearance of apoptotic cells, hepatic fibrosis, and liver regeneration. (HEPATOLOGY 2009.) [source] Interleukin-6 from intrahepatic cells of bone marrow origin is required for normal murine liver regenerationHEPATOLOGY, Issue 1 2002Xavier Aldeguer Interleukin-6 (IL-6) is required for normal liver regeneration, but the specific cellular source of this growth factor is unknown. We investigated whether this signal originates from the resident macrophage, the Kupffer cell. Using a murine model of bone marrow transplantation, we replaced recipient bone marrow,derived cells, including Kupffer cells, with cells of donor genetic phenotype. Recipients deficient in IL-6 (IL-6,/,) were lethally irradiated, then rescued with 107 donor bone marrow cells capable of expressing IL-6 (IL-6+/+). Conversely, IL-6+/+ recipients received IL-6,/, marrow. Successful engraftment was measured by the presence of the Y chromosome SRY locus in the livers of female recipients receiving male marrow, in situ IL-6 expression by Kupffer cells, and up-regulation of IL-6 in splenocytes after activation with lipopolysaccharide (LPS). Kupffer cell isolation in IL-6,/, females receiving IL-6+/+ male marrow clearly showed the presence of the SRY locus and IL-6 disrupted allele, whereas males receiving female marrow demonstrated no SRY or IL-6 signals, confirming the extent of replacement. Replacement of these cells in IL-6,/, mice with IL-6+/+ bone marrow successfully restored the regenerative response after partial hepatectomy (PHx) as indicated by signal transduction and activator of transcription 3 (STAT3) activation and hepatocyte DNA replication. Alternatively, complete replacement of Kupffer cells in IL-6+/+ mice by transplantation with IL-6,/, cells significantly inhibited liver regeneration and was partially restored by administration of IL-6. This investigation demonstrates a paracrine mechanism by which cells of bone marrow origin, most likely Kupffer cells, regulate the regenerative capacity of the hepatocyte through IL-6 expression. [source] Phosphorylcholine-Coated Circuits Improve Preservation of Platelet Count and Reduce Expression of Proinflammatory Cytokines in CABG: A Prospective Randomized TrialJOURNAL OF CARDIAC SURGERY, Issue 4 2009Costas J. Schulze M.D. Phosphorylcholine (PC) is a new-generation coating material designed to ameliorate biocompatibility and thereby to reduce the detrimental interactions of CPB. We studied the effects of PC-coated perfusion circuits on platelet function and the humoral and cellular response to CPB. Methods: Thirty patients undergoing coronary artery bypass grafting were randomized to PC-coated (PC group, n = 15) and noncoated (control group, n = 15) circuit groups. Clinical data, total blood loss, and pre- and postoperative platelet counts were recorded and IL-6 and TNF-,, CD41a, CD42b, and CD62p were measured at induction of anesthesia, after the initiation of CPB and at termination of CPB. Results: There was a significantly improved preservation of platelet count following CPB in the PC group (p = 0.028), which was sustained over a period of 72 hours. The use of PC-coated circuits further resulted in a significant attenuation of TNF-, and IL-6 expression (p < 0.05 and p < 0.01); however, we were unable to detect any differences in clinical outcomes. Conclusions: Despite similar clinical outcome, the obvious reduction of cytokine expression and improved preservation of platelet count suggest superior biocompatibility of PC-coated circuits. [source] Gene regulation of ,4,2 nicotinic receptors: microarray analysis of nicotine-induced receptor up-regulation and anti-inflammatory effectsJOURNAL OF NEUROCHEMISTRY, Issue 3 2009Vishnu Hosur Abstract ,4,2 Nicotinic acetylcholine receptors play an important role in the reward pathways for nicotine. We investigated whether receptor up-regulation of ,4,2 nicotinic acetylcholine receptors involves expression changes for non-receptor genes. In a microarray analysis, 10 ,M nicotine altered expression of 41 genes at 0.25, 1, 8 and 24 h in h,4,2 SH-EP1 cells. The maximum number of gene changes occurred at 8 h, around the initial increase in 3[H]-cytisine binding. Quantitative RT-PCR corroborated gene induction of endoplasmic reticulum proteins CRELD2, PDIA6, and HERPUD1, and suppression of the pro-inflammatory cytokines IL-1, and IL-6. Nicotine suppresses IL-1, and IL-6 expression at least in part by inhibiting NF,B activation. Antagonists dihydro-,-erythroidine and mecamylamine blocked these nicotine-induced changes showing that receptor activation is required. Antagonists alone or in combination with nicotine suppressed CRELD2 message while increasing ,4,2 binding. Additionally, small interfering RNA knockdown of CRELD2 increased basal ,4,2 receptor expression, and antagonists decreased CRELD2 expression even in the absence of ,4,2 receptors. These data suggest that endoplasmic reticulum proteins such as CRELD2 can regulate ,4,2 expression, and may explain antagonist actions in nicotine-induced receptor up-regulation. Further, the unexpected finding that nicotine suppresses inflammatory cytokines suggests that nicotinic ,4,2 receptor activation promotes anti-inflammatory effects similar to ,7 receptor activation. [source] Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseasesJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2010J. H. Ross Ross JH, Hardy DC, Schuyler CA, Slate EH, Mize TW, Huang Y. Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. J Periodont Res 2010; 45: 688,694. © 2010 John Wiley & Sons A/S Background and Objective:, Epidemiological studies have established that patients with diabetes have an increased prevalence and severity of periodontal disease. Interleukin (IL)-6, a multifunctional cytokine, plays a role in the tissue inflammation that characterizes periodontal disease. Our recent study has shown a trend of increase in periodontal IL-6 expression at the mRNA level across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. However, the periodontal IL-6 expression at the protein level in these patients has not been investigated. Material and Methods:, Periodontal tissue specimens were collected from eight patients without periodontal disease and diabetes (group 1), from 17 patients with periodontal disease alone (group 2) and from 10 patients with both periodontal disease and diabetes (group 3). The frozen sections were prepared from these tissue specimens and IL-6 protein expression was detected and quantified. Results:, The nonparametric Kruskal,Wallis test showed that the difference in IL-6 protein levels among the three groups was statistically significant (p = 0.035). Nonparametric analysis using the Jonckheere,Terpstra test showed a tendency of increase in periodontal IL-6 protein levels across group 1 to group 2 to group 3 (p = 0.006). Parametric analysis of variance (ANOVA) on IL-6 protein levels showed that neither age nor gender significantly affected the difference of IL-6 levels among the groups. Conclusion:, Periodontal IL-6 expression at the protein level is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. [source] Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney diseaseNEPHROLOGY, Issue 3 2010PAOLO FERRARI ABSTRACT Aim: To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin-6 (IL-6) and improved iron mobilization. Background: CKD patients may have elevated IL-6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL-6 expression. Methods: We studied 14 patients with stages 4,5 CKD (glomerular filtration rate <30mL/min per 1.73 m2) due to non-inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin-stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run-in period of 3 weeks and during 4 weeks of pentoxifylline treatment. Results: Ten patients (eGFR 23 ± 6 mL/min) completed the study. At the end of the run-in period average haemoglobin was 111 ± 5 g/L, ferritin 92 ± 26 µg/L, transferrin saturation 15 ± 3% and circulating IL-6 10.6 ± 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL-6 (6.6 ± 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 ± 5%, P < 0.003) and decreased serum ferritin (81 ± 25 µg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 ± 6 g/L by week 4 (P < 0.001). Conclusions: Pentoxifylline reduces circulating IL-6 and improves haemoglobin in non-inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin. [source] Interleukin-6 involvement in brain arteriovenous malformationsANNALS OF NEUROLOGY, Issue 1 2006Yongmei Chen MD We recently reported that the GG genotype of the interleukin-6 (IL-6),174G>C promoter polymorphism is associated with clinical presentation of intracranial hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we investigated whether tissue IL-6 expression was associated with IL-6,174G>C genotype, and whether IL-6 was linked to downstream targets involved in angiogenesis and vascular instability. Our results showed that the highest IL-6 protein levels in brain AVM tissue were associated with IL-6,174GG genotype (GG: 57.7 ± 20.2; GC: 35.6 ± 26.6; CC: 13.9 ± 10.2pg/mg; p = 0.001). IL-6 protein levels were increased in AVM tissue from patients with hemorrhagic presentation compared with patients without hemorrhage (55 ± 22 vs 40 ± 27pg/mg; p = 0.038). IL-6 messenger RNA expression strongly correlated with messenger RNA levels of IL-1,, tumor necrosis factor-,, IL-8, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-12. We further investigated the plausibility of IL-6 being an upstream cytokine responsible for initiating the angiogenic cascade by cell culture and animal experiments. IL-6 induced MMP-3 and MMP-9 expression and activity in mouse brain and increased proliferation and migration of cerebral endothelial cells. Together, our results suggest that the IL-6 genotype associated with intracranial hemorrhage modulates IL-6 expression in brain AVM tissue, which is consistent with the hypothesis that inflammatory processes induce angiogenic activity possibly contributory to brain AVM intracranial hemorrhage. Ann Neurol 2005 [source] Aurothiomalate inhibits cyclooxygenase 2, matrix metalloproteinase 3, and interleukin-6 expression in chondrocytes by increasing MAPK phosphatase 1 expression and decreasing p38 phosphorylation: MAPK phosphatase 1 as a novel target for antirheumatic drugsARTHRITIS & RHEUMATISM, Issue 6 2010Riina Nieminen Objective Aurothiomalate is a disease-modifying antirheumatic drug that suppresses inflammation and retards cartilage degradation and bone erosion in arthritis. The molecular mechanisms of action of aurothiomalate are not known in detail. MAPK pathways are major signaling pathways in inflammation that regulate the production of many inflammatory and destructive factors in arthritis. The purpose of the present study was to investigate the effects of aurothiomalate on the activity of p38 MAPK and on the expression of MAPK phosphatase 1 (MKP-1), cyclooxygenase 2 (COX-2), matrix metalloproteinase 3 (MMP-3), and interleukin-6 (IL-6) in immortalized murine H4 chondrocytes and in intact human and murine cartilage. Methods Protein expression was examined by Western blotting or by enzyme-linked immunosorbent assay, and messenger RNA (mRNA) expression was examined by real-time reverse transcription,polymerase chain reaction analysis. The mediator role of MKP-1 was investigated by using small interfering RNA (siRNA) methods to down-regulated MKP-1 expression in chondrocytes in culture and by comparing the responses in intact cartilage from MKP-1,deficient and wild-type mice. The effects of aurothiomalate were also confirmed in human rheumatoid cartilage by using tissue samples obtained at the time of total knee replacement surgery. Results Aurothiomalate inhibited IL-1,,induced COX-2 expression and prostaglandin E2 production by destabilizing COX-2 mRNA, as did the p38 MAPK inhibitor SB203580. Interestingly, aurothiomalate also increased the expression of MKP-1 and reduced the IL-1,,induced phosphorylation of p38 MAPK. Knockdown of MKP-1 by siRNA significantly impaired the ability of aurothiomalate to inhibit the phosphorylation of p38 MAPK and the expression of COX-2, MMP-3, and IL-6. Likewise, aurothiomalate reduced COX-2, MMP-3, and IL-6 expression in articular cartilage from patients with rheumatoid arthritis, as well as in articular cartilage from wild-type mice but not from MKP-1,/, mice. Conclusion Our findings indicate a novel mechanism for the antiinflammatory and antierosive actions of aurothiomalate, through increased expression of MKP-1, which leads to reduced activation of p38 MAPK and suppressed expression of COX-2, MMP-3, and IL-6. The results suggest that manipulation of MKP-1 levels is a promising new mechanism to be directed in the search and development of novel antiinflammatory and antierosive compounds that have the good efficacy of gold compounds but not their toxicity. [source] Comparison of synovial tissues from the knee joints and the small joints of rheumatoid arthritis patients: Implications for pathogenesis and evaluation of treatmentARTHRITIS & RHEUMATISM, Issue 8 2002Maarten C. Kraan Objective Serial synovial biopsy samples are increasingly being used for the evaluation of novel therapies for rheumatoid arthritis (RA). Most studies have used tissues from knee biopsies, but technical improvements have made serial small joint arthroscopy feasible as well. Theoretically, there could be differences in the features of synovial inflammation between various joints as a result of mechanical factors, differences in innervation, and other factors. We therefore undertook this study to compare the cell infiltrate in paired synovial biopsy samples from inflamed knee joints and paired inflamed small joints of patients with RA. Methods Nine RA patients with both an inflamed knee joint and an inflamed small joint (wrist or metacarpophalangeal joint) underwent an arthroscopic synovial biopsy of both joints on the same day. Multiple biopsy specimens were collected and stained for macrophages, T cells, plasma cells, fibroblast-like synoviocytes, and interleukin-6 (IL-6) by immunohistochemistry. Sections were evaluated by digital image analysis. Results There were no significant differences in mean cell numbers for all markers investigated in samples from the knee joint compared with samples from the small joints. We detected statistically significant correlations for the numbers of sublining macrophages, T cells, and plasma cells, as well as for IL-6 expression, between the knee joint and the small joints. However, there was no significant correlation between different joints for the numbers of intimal macrophages or fibroblast-like synoviocytes. Conclusion The results of this study show that the inflammation in one inflamed joint is generally representative of that in other inflamed joints. Therefore, it is possible to use serial samples from the same joint, selecting either large or small joints, for the evaluation of antirheumatic therapies. [source] Pulsed electromagnetic fields stimulation affects BMD and local factor production of rats with disuse osteoporosisBIOELECTROMAGNETICS, Issue 2 2010Wei-Wei Shen Abstract Pulsed electromagnetic fields (PEMF) have been used widely to treat nonunion fractures and related problems in bone healing, as a biological and physical method. With the use of Helmholtz coils and PEMF stimulators to generate uniform time-varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on bone mineral density (BMD) and local factor production in disuse osteoporosis (DOP) rats were investigated. Eighty 4-month-old female Sprague Dawley (SD) rats were randomly divided into intact (INT) group, DOP group, calcitonin-treated (CT) group, and PEMF stimulation group. The right hindlimbs of all the rats were immobilized by tibia-tail fixation except for those rats in the INT group. Rats in the CT group were injected with calcitonin (2,IU/kg, i.p., once a day) and rats in the PEMF group were irradiated with PEMF immediately postoperative. The BMD, serum transforming growth factor-beta 1 (TGF-,1), and interleukin-6 (IL-6) concentration of the proximal femur were measured 1, 2, 4, and 8 weeks after treatment. Compared with the CT and DOP groups, the BMD and serum TGF-,1 concentration in the PEMF group increased significantly after 8 weeks. The IL-6 concentration in the DOP group was elevated significantly after operation. The PEMF group showed significantly lower IL-6 level than the DOP group. The results found demonstrate that PEMF stimulation can efficiently suppress bone mass loss. We, therefore, conclude that PEMF may affect bone remodeling process through promoting TGF-,1 secretion and inhibiting IL-6 expression. Bioelectromagnetics 31:113,119, 2010. © 2009 Wiley-Liss, Inc. [source] Promotion of stem cell proliferation by vegetable peptoneCELL PROLIFERATION, Issue 5 2009J. Lee Objectives:, Technical limitations and evolution of therapeutic applications for cell culture-derived products have accelerated elimination of animal-derived constituents from such products to minimize inadvertent introduction of microbial contaminants, such as fungi, bacteria or viruses. The study described here was conducted to investigate the proliferative effect of vegetable peptone on adult stem cells in the absence of serum, and its possible mechanisms of action. Materials and methods:, Cell viability and proliferation were determined using the MTT assay and Click-iTÔ EdU flow cytometry, respectively. In addition, changes in expression of cytokine genes were analysed using MILLIPLEXÔ human cytokine enzyme-linked immunosorbent assay kit. Results:, Viability of cord blood-derived mesenchymal stem cells (CB-MSC) and adipose tissue-derived stem cells (ADSC) increased significantly when treated with the peptone. In addition, median value of the group treated with peptone shifted to the right when compared to the untreated control group. Furthermore, quantitative analysis of the cytokines revealed that production of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-,1), and interleukin-6 (IL-6) increased significantly in response to treatment with our vegetable peptone in both CB-MSCs and ADSCs. Conclusions:, Our findings revealed that the vegetable peptone promotes proliferation of CB-MSCs and ADSCs. In addition, results of this study suggest that induction of stem cell proliferation by vegetable peptone is likely to be related to its induction of VEGF, TGF-,1, and IL-6 expression. [source] Induction of glucocorticoid receptor-, expression in epithelial cells of asthmatic airways by T-helper type 17 cytokinesCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2010A. Vazquez-Tello Summary Background Corticosteroid insensitivity in asthmatics is associated with an increased expression of glucocorticoid receptor-, (GR-,) in many cell types. T-helper type 17 (Th17) cytokine (IL-17A and F) expressions increase in mild and in difficult-to-treat asthma. We hypothesize that IL-17A and F cytokines alone or in combination, induce the expression of GR-, in bronchial epithelial cells. Objectives To confirm the expression of the GR-, and IL-17 cytokines in the airways of normal subjects and mild asthmatics and to examine the effect of cytokines IL-17A and F on the expression of GR-, in bronchial epithelial cells obtained from normal subjects and asthmatic patients. Methods The expression of IL-17A and F, GR-, and GR-, was analysed in bronchial biopsies from mild asthmatics and normal subjects by Q-RT-PCR. Immunohistochemistry for IL-17 and GR-, was performed in bronchial biopsies from normal and asthmatic subjects. The expression of IL-6 in response to IL-17A and F and dexamethasone was determined by Q-RT-PCR using primary airway epithelial cells from normal and asthmatic subjects. Results We detected significantly higher levels of IL-17A mRNA expression in the bronchial biopsies from mild asthmatics, compared with normal. GR-, expression was significantly lower in the biopsies from asthmatics compared with controls. The expression of IL-17F and GR-, in biopsies from asthmatics was not significantly different from that of controls. Using primary epithelial cells isolated from normal subjects and asthmatics, we found an increased expression of GR-, in response to IL-17A and F in the cells from asthmatics (P0.05). This effect was only partially significant in the normal cells. Dexamethasone significantly decreased the IL-17-induced IL-6 expression in cells from normal individuals but not in those from asthmatics (P0.05). Conclusion Evidence of an increased GR-, expression in epithelial cells following IL-17 stimulation suggests a possible role for Th17-associated cytokines in the mechanism of steroid hypo-responsiveness in asthmatic subjects. Cite this as: A. Vazquez-Tello, A. Semlali, J. Chakir, J. G. Martin, D. Y. Leung, D. H. Eidelman and Q. Hamid, Clinical & Experimental Allergy, 2010 (40) 1312,1322. [source] Thymoquinone decreases AGE-induced NF- ,B activation in proximal tubular epithelial cellsPHYTOTHERAPY RESEARCH, Issue 9 2007Ahmed Amir Radwan Sayed Abstract The inhibitory effects of thymoquinone (TQ) on activation of the redox-sensitive transcription factor nuclear factor kappa B (NF- ,B) and interleukin-6 (IL-6) were studied in vitro. Human proximal tubular epithelial cells (pTECs) were cultivated and stimulated with advanced glycation end products (AGEs) and the effects of TQ were studied. A significant reduction of AGE-induced NF- ,B-activation and Il-6 expression was observed. This points to potential antioxidative qualities of TQ. Copyright © 2007 John Wiley & Sons, Ltd. [source] | |||||||||||||