Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The capacity of human cultured mesangial cells to produce soluble factors potentially relevant for mechanisms of inflammation and immunity at the glomerular site was analyzed. The nature of the secreted factors initially was investigated by Northern blot analysis using total cellular RNAs isolated from resting and activated mesangial cells. On exposure of mesangial cells to human recombinant interleukin-1 beta (IL-1 beta), high levels of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) mRNAs were detected. Similar transcripts were found after stimulation with human recombinant tumor necrosis factor-alpha (TNF-alpha). Active secretion of IL-8 was documented by radioimmunoassay in supernatants of mesangial cells activated by either IL-1 beta or TNF-alpha. Using an in vitro migration assay, supernatants from resting mesangial cells were found to be devoid of any chemotactic activity for granulocytes or monocytes. On stimulation with IL-1 beta, however, mesangial cell supernatants expressed MCP-1 biologic activity detected as induction of a strong migratory response for human monocytes but not for granulocytes. In addition, IL-1 beta and TNF-alpha induced high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) mRNAs. Similarly IL-1 beta and TNF-alpha induced the interleukin-6 (IL-6) gene and active secretion of its mature protein. These data strongly support an effector role for mesangial cells in modulating immune-inflammatory responses in glomeruli. Release of cytokines may activate not only infiltrating inflammatory cells through short paracrine pathways, but also mesangial cells themselves through an autocrine pathway.
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PMID:Interleukin-1 beta and tumor necrosis factor-alpha induce gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells. 201 80

A number of cytokines are active during the evolution of an inflammatory response, including tumor necrosis factor-alpha, interleukin-1, and novel chemotactic cytokines. This latter group of mediators belong to supergene families of inflammatory signals that play a key role in the selective recruitment of immune cells. In this presentation, we present data demonstrating, for the first time, endothelial cell expression of monocyte chemotactic protein (MCP) mRNA induced by LPS, interleukin-1 or tumor necrosis factor. Human fibroblasts were also found to express monocyte chemotactic factor mRNA in response to interleukin-1 or tumor necrosis factor, but LPS was not effective. In addition, neither primary cultures expressed MCP in response to interleukin-6. These studies demonstrate that non-immune "bystander" cells can play an active role in the recruitment of inflammatory cells via the production of novel chemotactic cytokines.
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PMID:Monocyte chemotactic protein gene expression by cytokine-treated human fibroblasts and endothelial cells. 278 88

Theoretic and in vitro evidence suggests that thrombosis and inflammation are interrelated. The purpose of the present study was to define the relationship between inflammation and deep venous thrombosis (DVT) in an in vivo model. Initiation of DVT was accomplished by administration of antibody to protein C (HPC4, 2 mg/kg) and tumor necrosis factor (TNF, 150 micrograms/kg); stasis; and subtle venous catheter injury. Thrombosis was assessed by thrombin-antithrombin assay (TAT), 125I-fibrinogen scanning (scan) over both the proximal and distal iliac veins, and ascending venography. Cytokines TNF, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8) were measured along with differential white blood cell counts, platelet counts, fibrinogen (FIB), and erythrocyte sedimentation rates (ESR). Baboon pairs were sacrificed on day 3 (T + 3d), T + 6d, and T + 9d and veins removed. All animals developed inferior vena cava and left iliofemoral DVT by venography; no right DVT was found. TAT was elevated by T + 1hr and peaked at T + 3hrs. Left iliofemoral DVT was found at T + 1hr by scan and reached a 20% uptake difference between the affected left and nonaffected right side at T + 3hrs. TNF peaked at T + 1hr; MCP-1 peaked at T + 6hrs; IL-8 and IL-6 peaked on T + 2d; all cytokines declined to baseline. TNF and TAT elevations were found to correlate with all cytokines; elevations in IL-8 were correlated with elevations in MCP-1 and IL-6 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inflammatory and procoagulant mediator interactions in an experimental baboon model of venous thrombosis. 845 29

Allograft rejection is the main cause of corneal graft failure. T lymphocytes and macrophages have been implied to be involved in corneal rejection, but little is known about the molecular mechanism in this process. In this study, cytokine mRNA expression in the cornea was analysed during experimental corneal transplantation. The donor and acceptor corneas of two groups of rats were studied after receiving an allo- (PVG to AO rat) or autograft (AO rat). For controls, central buttons and peripheral corneal rings of the non-transplanted contralateral eyes were used. At different post-operative days (1, 3, 7, 12 and 19), the corneas were removed and subjected to mRNA isolation. All corneal samples underwent semi-quantitative reverse transcriptase-polymerase chain reaction analysis for interleukin-1 beta, interleukin-1, receptor antagonist, interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-alpha, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA expression. Corneal rejection, characterized by opaque corneas with prominent neovascularization, was always diagnosed around day 12. Contralateral, non-grafted corneas showed constitutive mRNA expression for interleukin-1 receptor antagonist and in a few samples also monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA was found. Both allo- and autografts expressed mRNA for the cytokines found in contralateral, non-grafted tissue, as well as for interleukin-1 beta, interleukin-6, interleukin-10 and tumor necrosis factor-alpha. In allografts, the mRNA levels for these cytokines remained constant throughout all post-operative days, with increased interleukin-6 mRNA expression after post-operative day 12. The analysis of the autografts revealed high cytokine mRNA levels until post-operative day 3 or 7, which decreased from then on, except for interleukin-1 receptor antagonist. mRNA for interleukin-2, interleukin-4 and interferon-gamma was not observed in autografts at any time point and in allografts, until post-operative day 12. Interleukin-2 and interferon-gamma mRNA showed maximal expression on POD 12, while in autografts, a marked decrease was observed after POD 3. IL-10 mRNA levels decreased immediately after POD 1 in autografted eyes. For TNF-alpha, an increased mRNA expression starting on POD 7 was found in recipient rings of allografted eyes, while in autografts a weak expression was seen in some samples. MIP-2 transcription increased on PAD 12, while in autografts, its expression was not markedly different from that detected in the contralateral, non-grafted peripheral cornea.
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PMID:Cytokine mRNA expression during experimental corneal allograft rejection. 894 52

M. Leukemia inhibitory factor (LIF). oncostatin M (OsM) and interleukin-6 (IL-6) are members of a cytokine family, which are produced by activated macrophages and glomerular mesangial cells. These cytokines have been implicated in the pathogenesis of glomerular inflammation, but their action on glomerular cells is presently unclear. Therefore, we examined the effects of IL-6, OsM and LIF on chemokine synthesis of rat mesangial cells in culture. While LIF as well as IL-6 up-regulated monocyte chemotactic protein-1 (MCP-1) mRNA expression, OsM showed no such effect. The induction of MCP-1 mRNA by LIF and IL-6 was transient, peaking at one to two hours and two to three hours, respectively, and returning to background levels within several hours. Induction of MCP-1 mRNA by LIF and IL-6 was strongly inhibited by dexamethasone. LIF activated STAT factors in mesangial cells, suggesting their involvement in signal transduction pathways that lead to LIF-stimulated up-regulation of MCP-1 mRNA. By contrast, LIF. IL-6 and OsM failed to affect the expression of the chemokines, macrophage inflammatory protein-2 (MIP-2) and RANTES. The rapid, transient and differential regulation of MCP-1 expression induced by LIF and IL-6 contrasted with uniformly powerful effects of the proinflammatory cytokines IL-1 beta and TNF alpha that induced all tested chemokines for prolonged time periods. These results suggest that the selective and transient induction of MCP-1 by LIF and IL-6 may play a role in the preferential attraction of monocytes to the injured glomerulus.
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PMID:Differential regulation of chemokines by leukemia inhibitory factor, interleukin-6 and oncostatin M. 918 63

Benzydamine is a non-steroidal antiinflammatory drug, devoid of activity on arachidonic acid metabolism, which is extensively used as a topical drug in inflammatory conditions, particularly for the treatment of bacterial vaginosis and Candida albicans-sustained vaginitis. In the present study the effects of benzydamine on the production of several inflammatory cytokines were examined in cultures of Candida albicans-stimulated human mononuclear cells. Benzydamine (6.25-50 microM) inhibited Candida-induced tumor necrosis factor-alpha and, to a lesser extent, interleukin-1 beta production, whereas it did not affect interleukin-6 release. Benzydamine also blocked monocyte chemotactic protein-1 secretion, but it did not affect interleukin-8 production. Unlike benzydamine, ibuprofen and naproxen, two non-steroidal antiinflammatory drugs also used topically, were unable to suppress inflammatory lymphokine production from Candida-activated mononuclear cells. These data suggest that benzydamine may be effective in local Candida infections at least in part by suppressing inflammatory cytokine and monokine production in the vaginal mucosa and consequently decreasing their levels in vaginal secretions.
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PMID:Benzydamine inhibits the release of tumor necrosis factor-alpha and monocyte chemotactic protein-1 by Candida albicans-stimulated human peripheral blood cells. 926 82

To clarify the relationship between cholesterol homeostasis and inflammation we studied the effect of hypercholesterolaemia on in vivo cytokine production and leukocyte migration, in a murine model of local inflammation. Hypercholesterolaemia reduced of 40% the leukocyte recruitment by inhibiting interleukin-6 and monocyte chemotactic protein-1 production in the pouch exudate, without affecting vascular permeability or leukocytes motility.
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PMID:Inhibition of HMG-CoA reductase activity by hypercholesterolaemia reduces leukocyte recruitment and MCP-1 production. 1088 Feb 57

Oncostatin M (OSM) is a multifunctional cytokine, a member of the interleukin-6/leukemia inhibitory factor (IL-6/LIF) family, that can regulate a number of connective-tissue cell types in vitro including cartilage and synovial tissue-derived fibroblasts, however its role in joint inflammation in vivo is not clear. We have analyzed murine OSM (muOSM) activity in vitro and in vivo in mouse joint tissue, to determine the potential role of this cytokine in local joint inflammation and pathology. The effects of muOSM and other IL-6/LIF cytokines on mouse synovial fibroblast cultures were assessed in vitro and showed induction of monocyte chemotactic protein-1, interleukin-6, and tissue inhibitor metalloproteinase-1, as well as enhancement of colony growth in soft agarose culture. Other IL-6/LIF cytokines including IL-6, LIF, or cardiotrophin-1, did not have such effects when tested at relatively high concentrations (20 ng/ml). To assess effects of muOSM in articular joints in vivo, we used recombinant adenovirus expressing muOSM cDNA (AdmuOSM) and injected purified recombinant virus (10(6) to 10(8) pfu) intra-articularly into the knees of various mouse strains. Histological analysis revealed dramatic alterations in the synovium but not in synovium of knees treated with the control virus Ad-dl70 or knees treated with Adm-IL-6 encoding biologically active murine IL-6. AdmuOSM effects were characterized by increases in the synovial cell proliferation, infiltration of mononuclear cells, and increases in extracellular matrix deposition that were evident at day 4, but much more marked at days 7, 14, and 21 after administration. The synovium took on characteristics similar to pannus and appeared to contact and invade cartilage. Collectively, these results provide good evidence that OSM regulates synovial fibroblast function differently than other IL-6-type cytokines, and can induce a proliferative invasive phenotype of synovium in vivo in mice on overexpression. We suggest that OSM may contribute to pathology in arthritis.
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PMID:Murine oncostatin M stimulates mouse synovial fibroblasts in vitro and induces inflammation and destruction in mouse joints in vivo. 1102 23

Cytokines produced by pancreatic acinar cells may mediate cell death and recruitment of inflammatory cells into pancreas in pancreatitis and other disorders. Here, we demonstrate mRNA expression for a number of cytokines in acini isolated from rat pancreas. Using RNA from microscopically selected individual cells, we confirmed the acinar cell as a source for cytokine expression. Competitive RT-PCR, Western blot analysis, and immunocytochemistry showed large amounts of monocyte chemotactic protein-1 and interleukin-6 compared with other cytokines. Cytokine expression was inhibited by either inhibitors of p38 mitogen-activated protein kinase (MAPK), SB-202190 and SB-203580, or (less strongly) by the transcription factor nuclear factor (NF)-kappaB inhibitor MG-132. A combination of SB-203580 and MG-132 inhibited mRNA expression of all cytokines by >90%. The results suggest a major role for p38 MAPK and involvement of NF-kappaB in cytokine expression in pancreatic acinar cells. In contrast to isolated acini, we detected no or very low cytokine expression in normal rat pancreas. Our results indicate that activation of p38 MAPK, transcription factors, and cytokines occurs during removal of the pancreas from the animal and isolation of acini.
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PMID:Activation of pancreatic acinar cells on isolation from tissue: cytokine upregulation via p38 MAP kinase. 1107 16

This study set out to clarify whether the inhibition of sterol or nonsterol derivatives arising from mevalonate biotransformation plays a major role in the in vivo anti-inflammatory action of statins. Hepatic synthesis of all these derivatives was inhibited in mice by administered statins, whereas squalestatin inhibited only sterol derivatives. Using a short-term treatment schedule, we found that statins reduced the hepatic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase without affecting blood cholesterol. This treatment inhibited lipopolysaccharide- and carrageenan-induced pouch leukocyte recruitment and the exudate production of interleukin-6, monocyte chemotactic protein-1, and RANTES. Coadministration of mevalonate reversed the effect of statin on leukocyte recruitment. The inhibition of sterol synthesis by squalestatin did not have any anti-inflammatory effect, indicating that the biosynthesis of nonsterol compounds arising from mevalonate is crucial for the in vivo regulation of cytokine and chemokine production by statins. Their inhibition by statins may account for the reported anti-inflammatory effects of these drugs and may provide a biochemical basis for the recently reported effects of statins in the prevention of cardiovascular disease and mortality.
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PMID:In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products. 1149 48


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