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

Metalloproteinases and their specific inhibitors, believed to play a role in extracellular matrix metabolism, are regulated by inflammatory cytokines. Here we have addressed the question of whether liver, the major site of synthesis of plasma proteinase inhibitors, is also capable of synthesizing the tissue inhibitor of metalloproteinase-1 (TIMP-1). We show at mRNA and protein levels that TIMP-1 is expressed in differentiated human hepatoma cells (HepG2) and that its synthesis is up-regulated by interleukin-6 (IL-6), transforming growth factor beta 1 and phorbol 12-myristate 13-acetate. The physiological role of this phenomenon is underlined by the fact that lipopolysaccharide administration into rats in vivo, as well as IL-6-stimulation of rat hepatocytes in primary culture, also leads to an increase of TIMP-1 mRNA in liver cells.
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PMID:Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in human hepatoma cells (HepG2). Up-regulation by interleukin-6 and transforming growth factor beta 1. 133 Jul 2

We have previously shown that changes in acute-phase protein glycosylation result from alterations occurring within hepatocytes as a result of regulation by cytokines, that the glycosylation patterns of proteins secreted by Hep 3B and Hep G2 cells respond differently to the crude mixtures of cytokines found in conditioned medium from LPS-stimulated monocytes, and that interleukin-6 (IL-6) causes increased concanavalin A (Con A) binding of alpha 1 protease inhibitor in Hep 3B cells and decreased Con A binding of this protein in Hep G2 cells. In the present study we found that transforming growth factor beta 1 (TGF-beta), like IL-6, led to secretion of forms of alpha 1-protease inhibitor with increased Con A binding in Hep 3B cells, and that IL-6 and TGF-beta in combination were additive. In contrast, in Hep G2 cells, TGF-beta had an effect opposite to that produced by IL-6, leading to secretion of forms of alpha 1-protease inhibitor with increased Con A binding. When employed in combination with IL-6. TGF-beta abolished the effect of that cytokine. These studies indicate that TGF-beta influences glycosylation of alpha 1-protease inhibitor in two human hepatoma cell lines in a manner that can be differentiated from that of IL-6. The identification of TGF-beta as a second defined cytokine capable of influencing glycoprotein glycosylation and the demonstration that the effect of one cytokine can be modulated by another cytokine support the view that changes in glycosylation of plasma proteins are mediated by combinations of cytokines.
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PMID:Transforming growth factor beta 1 influences glycosylation of alpha 1-protease inhibitor in human hepatoma cell lines. 217 6

We studied the effect of transforming growth factor beta 1 (TGF beta 1) on mouse placental lactogen (mPL)-I and mPL-II secretion by primary cultures of placental cells from Days 7, 9, and 12 of pregnancy. We also studied the effects of co-incubation of epidermal growth factor (EGF) or interleukin-6 (IL-6) with TGF beta 1 on mPL-I and mPL-II secretion. TGF beta 1 at 10 ng/ml did not affect mPL-I secretion by cells from Days 7 or 9 of pregnancy or mPL-II secretion by cells from Day 7 of pregnancy but significantly inhibited mPL-II secretion by cells from Days 9 or 12 of pregnancy. The lowest concentration of TGF beta 1 that significantly inhibited mPL-II secretion by cells from Days 9 or 12 of pregnancy was 1 ng/ml. Immunocytochemistry for mPL-II indicated that treatment of placental cells from Day 12 of pregnancy with 10 ng/ml TGF beta 1 significantly reduced the number of mPL-II-containing cells. Inhibition of mPL-II secretion by TGF beta 1 was eliminated completely by addition of an anti-TGF beta 1 antibody. Northern analysis showed that steady state levels of mPL-II mRNA were not reduced by incubation of placental cells from Day 12 of pregnancy with 10 ng/ml TGF beta 1 for 5 days. EGF at 10 ng/ml significantly inhibited mPL-II secretion by cells from Day 7 of pregnancy, and addition of 10 ng/ml TGF beta 1, which did not itself inhibit mPL-II secretion by those cells, enhanced the inhibition by EGF of mPL-II secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Posttranscriptional inhibition of mouse placental lactogen-II secretion by transforming growth factor beta 1: synergistic effects with epidermal growth factor and interleukin-6. 749 90

Because fibronectin (FN) is known to be present in membranes in proliferative vitreoretinopathy, we sought to identify cytokines that regulate the release of FN by retinal pigment epithelial cells (RPE). Levels of FN in the supernatant of cultured human RPE cells were quantified with an ELISA, after which the cells were stimulated with human recombinant cytokines, interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interferon gamma (IFN-gamma), transforming growth factor beta 1 and 2 (TGF-beta), and phorbol myristate acetate (PMA). Protein kinase C (PKC) was blocked by 2 nM calphostin C or 1 mM staurosporine. RPE cells released FN into the supernatant constitutively. TGF-beta 1 and TGF-beta 2 upregulated the FN release in a dose- and time-dependent manner. The other cytokines tested were without effect. In combination, IFN-gamma and IL-1 beta reduced the effect of TGF-beta. PMA, which is a PKC activator, also increased the release of FN in a dose-dependent manner. Blocking of PKC with specific inhibitors abolished the effects of TGF-beta and PMA. The results show that TGF-beta is a potent stimulator of FN release by RPE cells, and exerts its effects via signal transduction involving PKC. Its effect is reduced by IFN-gamma.
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PMID:Cytokine effect on fibronectin release by retinal pigment epithelial cells. 795 9

We analyzed the response of human astrocytoma cell line U373-MG to various cytokines by measuring the production of interleukin-6 (IL6) mRNA and cytokine protein. Interferon gamma (IFN gamma), transforming growth factor beta 1 (TGF-beta 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF) did not induce IL6 mRNA production; however, IL6 mRNA expression and protein production was strongly induced by IL1 alpha and to a lesser extent by IFN alpha. The IL6 mRNA expression induced by IL1 alpha was potentiated by TGF-beta 1 and IFN alpha and slightly decreased by IFN gamma. The potentiation of cytokine mRNA accumulation by TGF-beta 1 was both time- and concentration-dependent. Induction of IL6 mRNA by IL1 alpha was optimally potentiated either if U373-MG cells were pretreated with TGF-beta 1 or if TGF-beta 1 was added within 30 min after stimulation with IL1 alpha. The potentiation of IL6 mRNA by TGF-beta 1 required de novo synthesis of an intermediate protein since treatment with cycloheximide abrogated the amount of mRNA enhanced by TGF-beta 1 without affecting IL1 alpha-driven mRNA production. Nuclear run-on analyses demonstrated increased transcriptional activity of the IL6 gene when stimulated with IL1 alpha in the presence of TGF-beta 1. However, actinomycin-D pulse chase experiments showed that TGF-beta 1 did not increase the stability of IL6 mRNA. Thus, in concert, the results demonstrate that TGF-beta 1 potentiates IL6 production in astrocytoma cells by promoting the transcriptional activity of the IL6 gene and requires coexpression of new proteins. Since cytokines can provide potent mitogenic signals to tumor cells, the results presented here further suggest that the antitumor effect of combination cytokine therapy might partly depend on heterotypic interactions between tumor cells and cytokines.
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PMID:Transforming growth factor beta-1 (TGF-beta 1) potentiates IL1 alpha-induced IL6 mRNA and cytokine protein production in a human astrocytoma cell line. 805 3

PTH and other hormones that stimulate resorption affect osteoclasts indirectly by modulating cytokine production by osteoblasts. However, the identity and role of the osteoblast-derived cytokines involved in this process are unclear. To examine which cytokines are regulated by PTH, we assessed cytokine mRNA levels in osteoblasts using the reverse transcription-polymerase chain reaction technique. Of the 16 cytokines we examined, unstimulated MC3T3-E1 osteoblastic cells expressed mRNA for interleukins 5, 6, and 7, macrophage and granulocyte-macrophage colony-stimulating factors, transforming growth factor beta 1, and leukemia inhibitory factor. PTH specifically increased expression of interleukin-6 (approximately 50-fold) and leukemia inhibitory factor (approximately 10-fold). Levels of both IL-6 and LIF mRNA peaked 30-60 minutes after addition of PTH and returned to baseline by 4-6 h. This rapid and transient mRNA response, which resembles that of immediate early genes, was also observed in primary rat osteoblasts. The transient mRNA response was accompanied by increased secretion of IL-6 protein. Lipopolysaccharide, another stimulator of resorption, increased mRNA levels of a group of cytokines that were not induced by PTH, namely interleukin-1 alpha, tumor necrosis factor alpha, and granulocyte-macrophage and granulocyte colony-stimulating factors. We conclude that osteoblasts produce complex networks of cytokines that (1) are regulated by bone-resorptive agents and (2) may be involved in controlling bone resorption.
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PMID:Regulation of cytokine expression in osteoblasts by parathyroid hormone: rapid stimulation of interleukin-6 and leukemia inhibitory factor mRNA. 825 53

Oral administration of cholera toxin (CT) induces a strong mucosal immune response to CT as well as having a potent adjuvant effect. Since one of the first cell types to encounter CT during cholera infection or after oral administration is the epithelial cell, we studied the effect of CT on interleukin-6 (IL-6) secretion by the rat intestinal epithelial cell line IEC-6. CT was found to rapidly enhance IL-6 secretion and IL-6 gene expression by these cells. The addition of dibutyryl cyclic AMP (cAMP) to cultures of IEC-6 cells had little effect on IL-6 secretion, yet mRNA levels were elevated, suggesting that the response may have been regulated by cAMP. Purified B subunit of CT did not significantly enhance IL-6 secretion or mRNA expression. CT and transforming growth factor beta 1 synergistically enhanced IL-6 secretion in IEC-6 cells. The addition of CT with either IL-1 beta or tumor necrosis factor alpha gave even greater synergistic enhancement of IL-6 secretion, and dibutyryl cAMP could mimic CT's synergy with IL-1 beta. These results indicate that the intestinal epithelial cell is capable of secreting high levels of IL-6 after encountering CT, especially in the presence of inflammatory cytokines. This high level of IL-6 secretion could be a very important component of the mucosal immune response to CT and may also account for a portion of the adjuvant effect of CT.
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PMID:Enhancing effect of cholera toxin on interleukin-6 secretion by IEC-6 intestinal epithelial cells: mode of action and augmenting effect of inflammatory cytokines. 840 61

Tissue inhibitor of metalloproteinases (TIMP) 1, 2 and 3 are related proteins that can form complexes with all known matrix metalloproteinases (MMPs). They inhibit the action of MMPs on extracellular matrix components. The balance of MMPs and TIMPs is important for tissue remodeling and its disturbance is believed to play a crucial role in pathophysiological processes such as tumor metastasis, destruction of cartilage and fibrosis. Cytokines and growth factors were found to regulate TIMPs and MMPs in a complex manner. In order to better understand the role of TIMPs in inflammatory joint diseases we have studied in vitro the regulation of TIMP-1 and TIMP-3 by inflammatory cytokines in cultured human synovial lining cells. We found that transforming growth factor beta 1 as well as interleukin-1 beta induce gene expression of both TIMP-1 and TIMP-3. In contrast, oncostatin M, an interleukin-6-type cytokine produced by activated T-lymphocytes and monocytes, had a differential effect on TIMP mRNA levels. After oncostatin M treatment, TIMP-1 expression was up-regulated but basal, as well as interleukin-1 beta-induced, TIMP-3 expression was inhibited. Interleukin-6 itself had no effect on synovial lining cells but a complex of interleukin-6 and the soluble interleukin-6 receptor induced activation of signal transducer and activator of transcription (STAT) factors in these cells and regulated TIMP-1 and TIMP-3 expression in a similar fashion as oncostatin M. Since TIMP-3 is matrix-associated whereas TIMP-1 is found in many body fluids, the role of oncostatin M during inflammatory processes might be to promote ECM degradation in the local environment but to prevent it systemically.
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PMID:Oncostatin M differentially regulates tissue inhibitors of metalloproteinases TIMP-1 and TIMP-3 gene expression in human synovial lining cells. 889 88

The malignant plasma cell in multiple myeloma expresses a monoclonal immunoglobulin (Ig) with a somatically mutated variable region. In humans, somatic hypermutation of Ig variable regions only occurs in mature B cells, during the helper T-cell (TH)-dependent germinal center (GC) reaction. Within this context, the major differentiation steps in normal B cells will be discussed: B-cell maturation, B-cell activation, the GC reaction--during which the B cells strongly proliferate and somatic hypermutation in conjunction with stringent cell selection leads to antibody affinity maturation--and the differentiation of B cells into plasma cells or memory cells. The myeloma cell resembles a normal plasma cell with regard to many of its biologic features, such as its homing to the bone marrow, interaction with stromal cells, or even its capacity to suppress hematopoiesis. While the expression of interleukin-6 (IL-6) and IL-10 disappears during normal differentiation of B cells into plasma cells, that of transforming growth factor beta 1 persists. Thus, normal plasma cells in principle could, like myeloma cells, suppress hematopoiesis if their proportion in the bone marrow greatly increased (this could occur, for example, in bone marrow aplasia). The specific key alteration leading to multiple myeloma still remains to be identified.
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PMID:Key differentiation steps in normal B cells and in myeloma cells. 912 41

To determine which factors are useful for the risk assessment of man-made fibers, we examined the gene expression of proinflammatory cytokines, growth factors, manganese superoxide dismutase (MnSOD), and inducible nitric oxide synthase (iNOS) in mineral fiber-exposed rats by means of reverse transcription-polymerase chain reaction (RT-PCR). Male Wistar rats received a single intratracheal instillation of either saline (control) or two types of fibers (2 mg of Union Internationale Centre le Cancer (UICC) chrysotile or alumina silicate refractory ceramic fiber [RCF]). Expression of interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), platelet-deriving growth factor-A, (PDGF-A), platelet-deriving growth factor-B (PDGF-B), transforming growth factor beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), MnSOD, and iNOS mRNA from lung and lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM) were assessed by RT-PCR. Among these factors, IL-1 alpha, TNF-alpha, IL-6, bFGF, and iNOS would be the possible parameters for the risk assessment of fibers. In a follow-up study, we investigated the time course (3 days, 1 week, 1 month, and 3 months) of expression of IL-1 alpha and TNF-alpha by LPS-stimulated AM exposed to mineral fibers in vivo. Male Wistar rats were instilled intratracheally with saline or fibers (2 mg of Union Internationale Contre le Cancer UICC crocidolite or potassium octatitanate whisker [TW]). The expression of IL-1 alpha mRNA by fibers was greatest in TW, crocidolite, chrysotile, and RCF-instilled rat AM, in that order. The increase of IL-1 alpha and TNF-alpha mRNA in AM peaked at 1 month and 3 days after exposure to crocidolite or TW, respectively. The expression of IL-1 alpha by fibers (crocidolite, chrysotile, TW, and RCF) may be a good indicator of the pathologic potential of fibers.
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PMID:Effects of mineral fibers on the expression of genes whose product may play a role in fiber pathogenesis. 940 Jul 19


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