UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xeroderma pigmentosum is a rare, autosomal recessive disease in which patients develop excessive solar damage at an early age and have a 1000-fold increased risk of developing cutaneous neoplasms. Xeroderma pigmentosum can be classified into seven complementation groups (A-G) with defects in different DNA nucleotide excision repair genes. Xeroderma pigmentosum patients also have impaired immune function including reduced natural killer cell activity and impaired induction of interferon-gamma. We hypothesized that altered cytokine induction may contribute to the immune defect in xeroderma pigmentosum patients. We examined cytokine mRNA expression after ultraviolet B irradiation using reverse transcriptase polymerase chain reaction in fibroblasts derived from five xeroderma pigmentosum patients in complementation groups A, C, and D and in complemented XP-A and XP-D cells. Cytokines interleukin-1beta and interleukin-6 displayed impaired ultraviolet B induction whereas interleukin-8 had normal induction in the xeroderma pigmentosum fibroblasts. Stable complementation of XP-A and XP-D cell lines increased ultraviolet-B-induced interleukin-1beta and interleukin-6 expression. These results demonstrate a deficient response of xeroderma pigmentosum fibroblasts to ultraviolet B in terms of cytokine interleukin-1beta and interleukin-6 induction but normal interleukin-8 induction and exhibit a role for DNA repair in cytokine induction.
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PMID:Impaired ultraviolet-B-induced cytokine induction in xeroderma pigmentosum fibroblasts. 1171 Sep 26

Severe combined immunodeficiency (SCID) mice were engrafted with rheumatoid arthritis (RA) synovium and evaluated to determine whether RA synovial morphology and function were maintained in the RA-SCID grafts. The four major components of RA synovitis, inflammation, immune reactivity, angiogenesis, and synovial hyperplasia persisted in RA-SCID grafts for 12 weeks. Retention of chronic inflammatory infiltrates was demonstrated by histological evaluation and by immunohistology for CD3, CD20, and CD68. Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia. Immune and inflammatory components were confirmed by the detection of human immunoglobulins and human interleukin-6 in serum samples obtained from grafted animals. Human blood vessels were detected by dense expression of CD31. Small vessels persistently expressed the vitronectin receptor, alpha v beta 3, a marker of angiogenesis. All vessels expressed VAP-1, a marker of activated endothelial cells. Finally, the grafts retained the ability to support immigration by human leukocytes, as demonstrated by the functional capacity to recruit adoptively transferred 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled T cells. T cells entering the RA-SCID grafts became activated and produced interferon-gamma, as detected by reverse transcriptase-polymerase chain reaction analysis. These studies demonstrate that the RA-SCID model maintains many of the phenotypic and functional features of the inflamed RA synovium.
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PMID:Inflammation, immune reactivity, and angiogenesis in a severe combined immunodeficiency model of rheumatoid arthritis. 1178 29

The aim of this study was focused on the analysis of gene expression of pro- and anti-inflammatory cytokines, and c-Myc in liver carcinogenesis in bile duct ligation (BDL)+furan treated rats. We also correlated the molecular and immunohistochemical findings with the degree of architecture distortion and histopathological changes in the liver. Groups of rats were subjected to BDL and one week later, animals were given furan in corn oil by gavage at 45 mg/kg body weight, once a week, five times weekly, for 1--4 weeks. Determination of pro- and anti-inflammatory cytokines gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) was performed in tissue, and liver sections were processed for immunohistochemistry of c-Myc. There was a significant increase in the TNF-alpha gene expression at the first week after BDL+furan treatment. Interleukin-6 gene expression was also increased at the first week and remained elevated up to the third week after treatment. C-Myc expression was detected beginning at the first week and peaking at fourth week after treatment where its expression was found at histologically distorted parenchymal areas. The present study suggest a possible relationship in the overexpression of pro-inflammatory cytokines and c-Myc in the development of carcinogenesis.
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PMID:Ductular hyperplasia is characterized by an over expression of c-Myc in bile duct ligation + furan injured rats: possible role of interleukin-6. 1181 52

Mast cell hyperplasia is observed in various inflammatory skin diseases. Although the mechanisms involved in the pathogenesis of these conditions remains largely uninvestigated, it is speculated that mediators produced in the lesional skin provide a favorable microenvironment for mast cell growth. Among the proinflammatory mediators, leukemia inhibitory factor (LIF), which shares a receptor component (gp130 subunit) with interleukin-6 (IL-6), has been identified as a mast cell growth-enhancing factor produced by cells of the keratinocyte-derived cell line (KCMH-1). In this study, we investigated the effect of four IL-6 family cytokines, IL-6, IL-11, oncostatin M (OSM) and LIF on mast cell growth in a mast cell/fibroblast co-culture system. When mouse bone marrow-derived cultured mast cells (BMMC) were maintained on a NIH/3T3 fibroblast monolayer, these cytokines induced proliferation of the mast cells, but none of the cytokines had any effect on mast cell proliferation in the absence of fibroblasts. mRNA for gp130 and receptors for the four IL-6 family cytokines were detected in NIH/3T3 fibroblasts by reverse transcriptase-mediated polymerase chain reaction. In contrast, only mRNA for the IL-11 receptor and gp130 were detected in BMMC. Tyrosine phosphorylation of gp130 was observed in NIH/3T3 fibroblasts after stimulation with all the cytokines. Some IL-6 family cytokines enhanced the production of stem cell factor (SCF), a potent mast cell growth factor, from NIH/3T3 fibroblasts, but the amount of SCF produced by NIH/3T3 fibroblasts was not paralleled by the mast cell growth-enhancement induced by the IL-6 family cytokines. When anti-SCF antibody was added with the IL-6 family cytokines in the BMMC/fibroblast coculture system, a significant effect of these cytokines remained, although the growth-enhancing activity was markedly reduced. A similar result was obtained when BMMC were prepared from W/W(V)-mice, which lack functional c-kit, in the BMMC/ fibroblast coculture system. These results suggest that IL-6 family cytokines stimulate mast cell growth by a fibroblast-dependent mechanism, and also suggest the existence of another pathway between BMMC and NIH/3T3 fibroblasts cooperating with the SCF/c-kit pathway. IL-6 family cytokines may thus contribute to mast cell hyperplasia in skin diseases.
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PMID:The IL-6 family cytokines, interleukin-6, interleukin-11, oncostatin M, and leukemia inhibitory factor, enhance mast cell growth through fibroblast-dependent pathway in mice. 1182 Jul 27

CD40-induced activation of cytokine gene expression in dendritic cells (DC) is an important process in the initiation of primary immune responses. We have determined the intracellular signaling events that lead to CD40 ligation-induced activation of interleukin-6 (IL-6) gene transcription in a murine DC line, FSDC, that is phenotypically representative of bone marrow-derived DC. IL-6 reverse transcriptase-PCR and promoter assays established the responsiveness of FSDC to anti-CD40 ligation. Further promoter assays showed that the transcription factors NF-kappaB and AP-1 are downstream transcriptional mediators of CD40-induced IL-6 gene expression. Anti-CD40 treatment of FSDC stimulated increased expression of specific NF-kappaB (p50:p65) and AP-1 (c-Jun, JunB, JunD, and c-Fos) DNA-protein complexes. Overexpression of an IkappaB-alpha super-repressor or a dominant negative JunD resulted in a strong inhibition of CD40-inducible IL-6 promoter activity supporting a role for both transcription factors. Upstream signal transduction events were studied by transfection of wild type and mutant human CD40 expression constructs into FSDC followed by stimulation with an anti-human CD40 antibody. These experiments revealed that anti-CD40 stimulation of NF-kappaB and IL-6 gene transcription requires specific amino acid residues in the cytoplasmic region of CD40 involved in the recruitment of TRAF2. Induction of IL-6 mRNA by anti-CD40 treatment was found to be a transient event (24 h) and was followed by a diminution of IL-6 transcript to levels below those found in unstimulated cells. This loss of IL-6 expression was associated with reduced p50:p65 NF-kappaB DNA binding and elevated binding of CBF1 to a site overlapping the NF-kappaB site. Overexpression of CBF1 resulted in a profound inhibition of basal and anti-CD40-induced IL-6 promoter activities indicating that prolonged induction of CBF1 may contribute to the transient nature of the IL-6 response. The physiological relevance of these molecular events to DC function is discussed.
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PMID:CD40 induces interleukin-6 gene transcription in dendritic cells: regulation by TRAF2, AP-1, NF-kappa B, AND CBF1. 1188 48

Serum soluble interleukin-6 receptors (sIL-6R) have been demonstrated to play an important role in hematopoiesis. We report here that serum sIL-6R levels reflect proliferative kinetics of the progenitors after stimulation by chemotherapy plus granulocyte colony-stimulating factor. Serum sIL-6R were serially evaluated in 26 courses of peripheral blood (PB) stem cell collections in 16 patients using enzyme-linked immunosorbent assay. Expressions of IL-6R and CD34 on PB mononuclear cells were examined by flow cytometric analysis and expressions of IL-6R mRNA were examined by reverse transcriptase polymerase chain reaction. There were no significant differences between the serum sIL-6R levels on day 0 in patients (27.8+/-2.1 ng/ml, mean +/- SEM) and those in controls (27.5+/-1.5 ng/ml). Following chemotherapy the serum sIL-6R levels were significantly decreased, reaching a minimal level on day 14 (22.3+/-1.2 ng/ml, p < 0.01) and then significantly increased to above the baseline levels on day 21 (32.0+/-2.1 ng/ml, p < 0.01). Similar oscillations in the number of white blood cells, IL6R+ cells, CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM) in PB could be observed and the peak expression of mRNA was compatible with the expression of antigen. Serum sIL-6R levels on day 17 and 19 were positively correlated with the number of CD34+ cells, IL-6R+ cells, CFU-GM in PB and the number of collected CD34+ cells in leukapheresis products. In addition, when comparing the 2 groups divided by the number of prior chemotherapies, the status of disease or dose of the mobilizing regimen, the serum sIL-6R levels were significantly increased after day 17 in the group that received fewer courses of prior chemotherapy, the group in complete remission and the group of high-dose chemotherapy. These findings indicated that sIL-6R levels do not reflect the hematopoietic ability in the steady state, or the capability of the hematopoiesis after stimulation. Thus, sIL-6R levels may be a marker for the timing of PBSC collection or the prediction of the number of collected CD34+ cells.
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PMID:Serum soluble IL-6 receptor levels during the mobilization of stem cells to peripheral blood. 1200 69

Hereditary gingival fibromatosis (HGF) is a rare oral condition characterized by a slow and progressive enlargement of the gingiva, involving both the maxilla and mandible. In vitro, HGF fibroblasts demonstrate a proliferative index significantly higher than fibroblasts from normal gingiva (NG). The objective of this study was to determine the effect of dihydrotestosterone on the proliferation of gingival fibroblasts derived from patients with HGF (n = 4) and from four healthy individuals. Additionally, we analyzed the effect of dihydrotestosterone on interleukin-6 (IL-6) production and determined the expression levels of androgen receptors in NG and HGF fibroblasts. Gingival fibroblasts from NG and HGF were incubated with increasing concentrations of dihydrotestosterone with or without androgen blockers, and cultured for 24 h, and the proliferation index was determined by automated cell counter. IL-6 production, in this system, was quantified using a "capture" enzyme-linked immunosorbent assay (ELISA). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to measure the mRNA expression of androgen receptors. The results indicated that dihydrotestosterone simultaneously downregulates the production of IL-6 and upregulates the cell proliferation. Finasteride and cyprosterone acetate, two anti-androgens, partially reversed these effects. Androgen receptor mRNA expression was identified in both NG and HGF fibroblasts; however, the levels in NG were higher than those observed in HGF. These results show that testosterone coordinates the proliferation and production of IL-6 of normal and HGF fibroblasts.
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PMID:Testosterone stimulates proliferation and inhibits interleukin-6 production of normal and hereditary gingival fibromatosis fibroblasts. 1203 Sep 72

Previous studies have suggested that the production of interleukin-6 (IL-6) is increased in the intestinal mucosa during inflammation, and that nuclear factor-kappaB (NF-kappaB) is an important regulator of the IL-6 gene in the enterocyte. We tested the hypothesis that sodium arsenite inhibits IL-6 production in stimulated enterocytes and that this effect of arsenite is caused by down-regulation of NF-kappaB activity. Cultured Caco-2 cells were treated with sodium arsenite and were then stimulated with IL-1beta. IL-6 production and gene expression were determined by ELISA and reverse transcriptase-PCR respectively. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay. IL-1beta increased NF-kappaB DNA binding activity, IL-6 mRNA levels and IL-6 production. These effects of IL-1beta were inhibited by treatment of the cells with sodium arsenite in a dose- and time-dependent fashion. When cells were transfected with a plasmid expressing the p65 subunit of NF-kappaB, the inhibitory effect of sodium arsenite on NF-kappaB activity and IL-6 production was blunted. These results suggest that sodium arsenite inhibits IL-6 production in enterocytes subjected to an inflammatory stimulus, and that this effect, at least in part, reflects down-regulated NF-kappaB activity.
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PMID:Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-kappaB activity. 1224 37

The novel human gene MIA2 encoding a melanoma inhibitory activity (MIA) homologous protein was identified by a GenBank(TM) search. MIA2, together with MIA, OTOR, and TANGO, belongs to the novel MIA gene family sharing important structural features, significant homology at both the nucleotide and protein levels, and similar genomic organization. In situ hybridization, reverse transcriptase-PCR, and Northern blots presented a highly tissue-specific MIA2 expression pattern in the liver. Promoter studies analyzing transcriptional regulation of MIA2 revealed an HNF-1-binding site at position -236 controlling hepatocyte-specific expression. Mutation of the site led to a complete loss of promoter activity in HepG2 cell. Further sites detected in the MIA2 promoter were consensus binding sites for SMAD and STAT3, Consistently, stimulation of MIA2 mRNA expression occurred by treatment with interleukin-6, transforming growth factor-beta, and conditioned medium from activated hepatic stellate cells. In accordance with these results, MIA2 mRNA was found to be increased in liver tissue of patients with chronic hepatitis C infection compared with controls. MIA2 mRNA levels were significantly higher in patients with severe fibrosis or inflammation than in patients with less severe fibrosis or inflammation. In summary our data indicate that MIA2 represents a potential novel acute phase protein and MIA2 expression responds to liver damage. The increased transcription in more severe chronic liver disease suggests that MIA2 may serve as a marker of hepatic disease activity and severity.
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PMID:Specific expression and regulation of the new melanoma inhibitory activity-related gene MIA2 in hepatocytes. 1258 26

Thrombin, a serine protease, plays an important role in the progression of atherosclerosis. How atorvastatin could limit the pro-inflammatory response to thrombin was studied in cultured rat aortic smooth muscle cells. The variations in expression of interleukin-6, heme oxygenase-1, p(22phox) and Mox-1 mRNAs were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Interleukin-6 release was determined using the B9 cell assay. Nuclear factor-kappa B (NF-kappaB) translocation was analysed by electrophoretic mobility shift assay (EMSA) and RhoA protein translocation by Western blot. Thrombin activated interleukin-6 secretion and mRNA expression in smooth muscle cells in a dose-dependent manner. The greatest effect on mRNA expression was obtained after 1 h of stimulation. Preincubation (72 h) of the cells with various concentrations of atorvastatin prevented this effect. Simultaneous addition of mevalonate overcame this statin effect. Thrombin was without effect on p(22phox) and heme oxygenase-1 mRNA expression but, after 3 h of stimulation, induced a two-fold increase in that of Mox-1. Preincubation with atorvastatin dose-dependently downregulated this Mox-1 mRNA expression. In addition, thrombin induced NF-kappaB translocation and membrane translocation of RhoA in smooth muscle cells which were both prevented by pre-treatment of the cells by atorvastatin. These data demonstrate the ability of atorvastatin to prevent the induction by thrombin of a pro-inflammatory phenotype in smooth muscle cells.
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PMID:Atorvastatin limits the pro-inflammatory response of rat aortic smooth muscle cells to thrombin. 1292 59

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