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)

Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), neutrophil-activating peptide-1/interleukin-8 (NAP-1/IL-8), and interleukin-6 (IL-6) are pivotal in the regulation of hematopoiesis and immune responses. In mesenchymal cells, their expression is induced by tumor necrosis factor alpha (TNF) and other agents. We now show that, while induction of cytokine expression by TNF in human lung fibroblasts was parallel, glucocorticoid hormones differentially affected their production. Dexamethasone (1 mumol/L) concordantly repressed expression of GM-CSF, NAP-1/IL-8 and IL-6. RNA and protein levels were reduced to approximately 5%, 20%, and 30% of control cells, respectively, as determined by Northern blot analyses and immunoassays. A 50% reduction of RNA levels for all three cytokines occurred in the range of 1 hour. In contrast, dexamethasone (1 mumol/L) did not decrease M-CSF RNA levels and protein release. M-CSF RNA and protein levels were maintained even when dexamethasone (1 mumol/L) was present for the whole duration of a 48-hour TNF stimulation. Further experiments showed that dexamethasone downregulates expression of GM-CSF, NAP-1/IL-8, and IL-6 mainly by decreasing the mRNA stability of these cytokines, and that the dexamethasone-mediated repression of cytokine expression depends on ongoing protein and RNA syntheses. Our study suggests that glucocorticoid hormones repress expression of a set of cytokine genes important in conditions of stress. However, they seem not to affect M-CSF expression, which is likely to be more crucial in maintaining long-term functions of myeloid cells.
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PMID:Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but not of M-CSF in human fibroblasts. 137 Feb 8

We have tested the hypothesis that the bronchial epithelium has the capacity to generate and release cytokines that could contribute to inflammatory events associated with inflammatory lung diseases. Messenger RNA (mRNA) for interleukin-6 (IL-6), IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) was identified in human bronchial epithelial cell primary cultures, characterized on the basis of staining for cytokeratin, using both in situ hybridization and Northern blotting. Using in situ hybridization we have shown that the majority of the cells expressed mRNA for IL-6 and IL-8, whereas fewer than 20% of cells expressed message for GM-CSF. The numbers of cells expressing message were increased by culture with tumour necrosis factor-alpha (TNF-alpha) (20 ng/ml, 24 hr). These observations were substantiated by Northern blotting, which showed that both TNF-alpha and IL-1 beta were able to induce a dose-dependent increase in IL-8-specific mRNA. Immunoreactive IL-6 and GM-CSF were detected and quantified in the culture supernatants by ELISA, and IL-8 by radioimmunoassay. The levels of immunoreactivity were increased by incubation of epithelial cells with either IL-1 beta or TNF-alpha for 24 hr. A transformed tracheal epithelial cell line (9HTEo-) expressed mRNA for IL-6, IL-8 and GM-CSF but, whereas levels of immunoreactive IL-6 in culture supernatants were comparable with those in primary cell cultures, levels of IL-8 were low and GM-CSF trivial. These observations indicate that the bronchial epithelium has the potential to be a major source of IL-8 and a number of other cytokines, and that production can be amplified substantially by IL-1 beta and TNF-alpha. The bronchial epithelium is ideally situated to modulate inflammatory and immunological events in and around the airways, and these observations suggest that it could contribute to promote and sustain inflammatory and immunological processes in inflammatory lung diseases such asthma.
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PMID:Expression and generation of interleukin-8, IL-6 and granulocyte-macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1 beta and tumour necrosis factor-alpha. 147 79

There is increasing experimental and clinical evidence that a number of cytokines play a major role in the response to injury and infection and in the development of organ damage in critically ill patients. Tumour necrosis factor (TNF) is now proposed to be a key mediator of organ injury during sepsis. It is elevated early in the course of septic shock and high levels correlate with unfavourable outcome. In animals it can produce the effects of endotoxin. The prophylactic administration of anti-TNF antisera protects mice and rabbits from lethal effects of lipopolysaccharide. Interleukin-1 (IL-1) is an endogenous pyrogen which induces leukocytosis and muscle catabolism. It causes hypotension and tachycardia by reducing smooth muscle contractility. IL-1 receptor blockers have been shown to diminish mortality in experimental endotoxic shock. Interleukin-6 (IL-6) is a pyrogen and lymphocyte activator. It is the major stimulus to acute phase protein production by the liver. A recently described neutrophil-activating peptide (Interleukin-8; IL-8) may be involved in the pathogenesis of ARDS. High blood levels of IL-8 have been found in patients with septic shock. Platelet-derived growth factor (PDGF) has been shown to stimulate TNF production, leukocyte chemotaxis and pulmonary vasoconstriction in response to endotoxin. Other cytokines and growth factors have not yet been studied in critical illness. The cytokine network can be either protective or damaging. Its activation during critical illness triggers complex and still poorly understood interactions. A better comprehension of its role in protection from infection and in the pathogenesis of multiple organ failure may allow therapeutic manipulations aimed at minimising adverse effects while retaining immunological protection.
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PMID:The cytokine network in the critically ill. 152 67

We investigated, in five cell strains per experiment, whether several cytokines known or believed to have effects on bone resorption were produced by nearly homogeneous strains of cultured normal human osteoblast-like (hOB) cells that display virtually the complete phenotype of the mature osteoblast. In unstimulated hOB cells, we detected constitutive production of interleukin-6 (IL-6) (mean +/- SE, 122 +/- 32 pg/ml) and IL-8 (135 +/- 39 pg/ml), but not of IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF alpha). IL-1 beta in doses from 1-100 U/ml stimulated dose-dependent increases in IL-6 (r = 0.87; P less than 0.001) and IL-8 (r = 0.95; P less than 0.001). Similar increases occurred after stimulation with TNF alpha in doses from 3-300 U/ml. IL-1 beta and TNF alpha also stimulated GM-CSF production, but only at higher doses. 17 beta-Estradiol (10(-8) M) had no significant effect on the secretion of any of these cytokines, either constitutively or after stimulation with IL-1 beta or TNF alpha. Stimulated production of IL-4 was not detected after treatment with IL-1 beta or TNF alpha, and that of TNF alpha was not detected after treatment with IL-1 beta. We conclude that IL-6, IL-8, and GM-CSF, but not IL-4 and TNF alpha, are produced by highly differentiated normal human cells of the osteoblast lineage, but their secretion is not regulated by estrogen. However, we cannot exclude the possibility that estrogen regulation of these cytokines may occur during early stages of osteoblast differentiation.
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PMID:Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 beta and tumor necrosis factor-alpha: lack of regulation by 17 beta-estradiol. 157 80

Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural cell-derived cytokines in allergic inflammation. 193 66

Interleukins (IL) are a heterogeneous class of cytokines involved in activation of T lymphocytes (IL-1, 2, 4, 6 and 7), B lymphocytes (IL-1, 2, 4, 5, 6 and 7), and macrophages (IL-1 and 4), and hematopoiesis (IL-1, 2, 3, 4, 5, 6 and 7), acting either by themselves, or as co-stimulator factors. Interleukin-1 (IL-1 alpha and IL-1 beta) is induced by different signals including microbial products; it mediates various events occurring during inflammation (e.g. fever, osteolysis, leucopenia, hypotension, hyperalgia, etc...). Such mechanisms are often the consequences of the induction by IL-1 of lipid mediators (e.g. prostaglandins, platelet activating factor, etc). IL-1 often acts synergistically with Tumor Necrosis Factor during the pro-inflammatory process. IL-1 as well as microbial products induces the production of interleukin-6 and interleukin-8. IL-6 also plays a role in inflammation, mainly as an inducer of acute phase proteins synthesis by hepatocytes. IL-8 has chemotactic and activating properties for neutrophils.
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PMID:[Interleukins and inflammation]. 230 78

Cytokine regulation was compared in three groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy; adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria. Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, TNF receptors (TNF R), and the TNF/TNF R ratios were significantly higher in severe malaria compared with uncomplicated malaria. High plasma levels of all immunoregulatory molecules were associated with slow cure after therapy. In all patients, phytohemagglutinin-induced cytokine production was depressed on admission compared with convalescence. A significant difference was the higher TNF production capacity in patients with severe malaria on day 2 and day 5 compared with that in patients with uncomplicated malaria. In contrast to IL-6 and IL-8, a high TNF production capacity during the acute phase of malaria predicted a rapid clinical and parasitologic cure in the patients. These findings illustrate the dual role of TNF in the protection and pathology of malaria.
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PMID:Prediction of accelerated cure in Plasmodium falciparum malaria by the elevated capacity of tumor necrosis factor production. 748 13

Cytokines and cellular adhesion molecules (CAMs) may play a role in the inflammatory and fibrotic processes underlying systemic sclerosis (SSc). We compared the immunohistological distribution of cytokines and CAMs in skin biopsies from 12 SSc patients and 14 normal (NL) individuals. Among CAMs, vascular cell adhesion molecule-1 (VCAM-1), which mediates leukocyte-endothelial adhesion, showed increased expression on SSc versus NL endothelium and stratum granulosum. P-selectin was up-regulated in SSc versus NL stratum granulosum. The CD44 lymphocyte homing receptor showed the most striking differences between SSc and NL: its expression was increased in SSc stratum granulosum, stratum spinosum, on lymphocytes, and macrophages. Regarding cytokines, interleukin-6 (IL-6) expression was increased on SSc versus NL endothelium and fibroblasts. Tumor necrosis factor-alpha (TNF-alpha) reactivity was more prevalent in SSc than NL stratum granulosum, whereas IL-8 expression was higher on SSc compared to NL endothelium. Some CAMs, such as VCAM-1 and P-selectin, and cytokines, namely TNF-alpha and IL-8, were more commonly found in skin biopsies taken from early (< or = 1 year's duration) SSc, while others, such as IL-6, showed up-regulation in the late stage of the disease. The results suggest that certain CAMs and cytokines may play a differential role in both the early, inflammatory, and the late, fibrotic stage of SSc.
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PMID:In situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic sclerosis. Their role in early and late disease. 750 81

Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1) is involved in the pathogenesis of toxic shock syndrome and perhaps other staphylococcal diseases. Recently, the C-terminal part of the TSST-1 toxin has been shown to be responsible for mitogenic activity in animal models. We studied the role of the C-terminal structural unit of TSST-1 with regard to proliferation, cytokine release (tumor necrosis factor alpha [TNF-alpha], interleukin-6 [IL-6], and IL-8), mRNA expression for IL-6, IL-8, IL-10, TNF-alpha, and CD40 ligand (CD40L), synthesis of immunoglobulin E (IgE), IgA, IgG, and IgM, CD23 expression, and soluble CD23 (sCD23) release from human peripheral blood mononuclear cells (PBMC). For this purpose, we used the recombinant wild-type TSST-1 (p17) mutant toxin Y115A (tyrosine residue modified to alanine) and toxin H135A (histidine residue modified to alanine). Unmodified toxin p17 and mutant toxin Y115A, at a concentration below 5 ng, to a lesser degree, induced a strong proliferation. Toxin p17 followed by toxin Y115A was the most pronounced inducer for mRNA expression for IL-10 and CD40L and cytokine generation (mRNA and protein) for TNF-alpha, IL-6, and IL-8. Mutant protein H135A failed to activate human PBMC. Both toxins p17 and, to a lesser degree, Y115A significantly suppressed IL-4- and anti-CD40-induced synthesis of all four Igs as well as IL-4-induced CD23 expression and sCD23 release. Mutant toxin H135A failed to do so. Thus, our data show that a region in the C terminus of TSST-1 is responsible not only for mitogenic activity but also for additional immunomodulating biological activities of TSST-1. More specifically, histidine residue H135A of the 194-amino-acid toxin appears to be critical for the expression of biological activities in a human in vitro model.
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PMID:Role of a carboxy-terminal site of toxic shock syndrome toxin 1 in eliciting immune responses of human peripheral blood mononuclear cells. 753 24

During the initial phase of respiratory syncytial virus (RSV) infection, when a low virus-cell ratio is most probable, signs of inflammation are detectable in the infected respiratory tissue. Therefore we analysed the release of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, tumour necrosis factor-alpha (TNF-alpha), and the soluble form of the TNF receptor-I (sTNFR-I), from peripheral blood mononuclear cells (PBMC) after exposure to low infectious RSV doses (multiplicity of infection, MOI, 0.001-1) and incubation times of up to 24 hr. The PBMC secreted IL-8 in a time- and virus dose-dependent fashion. As was verified by Northern blot analysis, the increased IL-8 secretion rate was accompanied by an enhanced IL-8 mRNA steady-state level. The infection of the PBMC after 4 hr post-RSV exposure was verified by detection of RSVSH genomic RNA and mRNA after reverse transcription and polymerase chain reaction (PCR) amplification. In addition, after 24 hr post-infection we determined the percentage of infected cells by specific immunofluorescence using monoclonal antibodies directed against the F- and G-proteins. After exposure of PBMC to inactivated RSV, we observed only RSVSH genomic RNA and a reduced IL-8 release. Thus, even the binding and/or phagocytosis of RSV by PBMC induced an IL-8 synthesis to some extent. Following an incubation time of 24 hr, PBMC exposed to small RSV doses synthesized and released high amounts of IL-6 into the cell supernatant. In contrast, only low amounts of TNF-alpha were released from PBMC. In addition to the release of the proinflammatory cytokines, an enhanced level of the sTNFR-I was measured in the cell supernatants at a MOI of 0.1. However, there was no correlation between TNFR-I membrane expression and cell supernatant concentration. Co-culture experiments performed with PBMC and human epithelial cells (A549) revealed that the enhanced IL-8 secretion profile observed in the coculture was partially dependent on the cytokines TNF-alpha, IL-1 beta and TNF-beta/lymphotoxin released by the cells themselves.
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PMID:Cytokine (IL-8, IL-6, TNF-alpha) and soluble TNF receptor-I release from human peripheral blood mononuclear cells after respiratory syncytial virus infection. 755 23


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