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

We investigated the gene expression of the alpha chain of C4b-binding protein (C4bp alpha) in a variety of tissues, and in liver cell and hepatoma lines. C4bp alpha mRNA was detected in the liver, but not in the other tissues examined. The constitutive gene expression of C4bp alpha by a hepatoma line, HepG2, was significantly augmented by treatment with monocyte-conditioned medium (MoCM), 12-O-tetradecanoylphorbol-13-acetate (TPA), interleukin-6 (IL6) and tumor necrosis factor (TNF) but not by a calcium ionophore (A23187) or interleukin-1 beta (IL1 beta).
 ...
PMID:Interleukin 6 and tumor necrosis factor fully activate liver-specific gene expression of the alpha chain of C4b-binding protein. 165 65

An anesthetized endotoxemic baboon model has been developed by infusing 2.0 mg E. coli endotoxin/kg i.v. over 1 hr (n = 7). Animals were monitored for 5-7 days with analyses of: cardiovascular, metabolic, and organ dysfunction; acid base, hemostatic, and hematological alterations; as well as tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels. Pathophysiologies detected at 2 hr included transient decreases in vascular resistance and blood pressure, a 157% increase in blood lactate, and a 90% decrease in circulating neutrophils. Organ dysfunction was not observed until 24 hr and, although thrombocytopenia was prevalent (-72% at 48 hr), disseminated intravascular coagulation (DIC) was not a major pathology. Hematocrit fell 21% by 24 hr and was -41% at 5-7 days. Serum TNF peaked at 90 min (7.8 +/- 0.2 ng/mL) and was undetectable after 3 hr. IL-6 also increased early, peaked at 3 hr (3872 +/- 846 U/mL) and was still detectable at 24 hr. A low mortality primate model of gram-negative sepsis has been developed that is characterized by early cardiovascular and metabolic dysfunction (2-6 hr), late organ dysfunction (24-48 hr), sub-clinical DIC, a prolonged anemia, and a 29% mortality between 48 and 72 hr.
 ...
PMID:Characterization of an endotoxemic baboon model of metabolic and organ dysfunction. 165 18

We have studied the effect of interleukin-6 (IL-6) on the binding of tumor necrosis factor (TNF) to various cell lines. A significant increase (up to 250%) in binding was observed on rat hepatocytes and on the human hepatoma cell line HepG2, while no changes in the number of cells or cell morphology could be observed. Scatchard plot analysis showed that IL-6 enhanced the number of TNF receptors without affecting the receptor affinity. The effect reached plateau levels after approximately 6 h and at IL-6 concentrations of 10 ng/ml. It could be completely eliminated by cotreatment of cells with anti-IL-6 antibodies, but not by treatment with anti-interferon-gamma (IFN-gamma), suggesting that IFN-gamma, which can enhance TNF receptor expression on a variety of cells, was not a mediator in this IL-6 effect. Treatment with inhibitors of protein or RNA synthesis completely abolished the IL-6-induced increase, suggesting that IL-6 caused an enhanced transcription of TNF receptor mRNA. IL-1 had no effect on TNF binding to HepG2. However, when cells were cotreated with IL-1 and IL-6, IL-1 could completely abrogate the IL-6 effect.
 ...
PMID:Interleukin-6 enhances the expression of tumor necrosis factor receptors on hepatoma cells and hepatocytes. 165 25

In this study, we investigated the influence of D-galactosamine (GalN), indomethacin, and dexamethasone on the pharmacokinetics of injected or induced tumor necrosis factor (TNF) and interleukin-6 (IL-6) after a bolus injection of murine TNF (mTNF) or lipopolysaccharide (LPS). It is well known that GalN treatment renders mice much more vulnerable to TNF or LPS lethality. Nevertheless, GalN had no influence on TNF clearance or IL-6 induction after mTNF injection; however, the induced TNF and IL-6 levels were considerably augmented by the GalN cotreatment when a high dose of LPS was injected (GalN was given as a single injection together with TNF or LPS). Indomethacin and dexamethasone, either of which shows a clear protection against TNF/LPS lethality in normal mice, did not change the clearance of injected mTNF, but both reduced the TNF-induced IL-6 levels. Indomethacin did not affect the level and clearance of LPS-induced TNF, whereas the induced IL-6 levels were significantly lower than in the control mice. The circulating TNF and IL-6 concentrations after LPS injection in mice pretreated with dexamethasone were very considerably reduced. Furthermore, neither agent had an influence on the number of TNF binding sites on hepatocytes. We conclude that the strongly enhanced sensitivity of GalN-treated mice towards mTNF-induced or LPS-induced lethality was not reflected in circulating TNF or IL-6 levels, and that dexamethasone and indomethacin both reduce circulating IL-6 concentrations in mice treated with TNF and LPS.
 ...
PMID:The influence of modulating substances on tumor necrosis factor and interleukin-6 levels after injection of murine tumor necrosis factor or lipopolysaccharide in mice. 165 27

Several oligopeptide segments of fimbrial subunit protein (fimbrilin) of Porphyromonas gingivalis strain 381 were synthesized and tested for immunobiological activities. Peptides F3(31-50; amino acid residue numbers 31 to 50, based on the amino acid sequence of the fimbrilin proposed by Dickinson et al., Infect. Immun., 170, 1658, 1988), F12(212-231) and F17(312-331) were found to be immunodominant epitopes of this fimbrial protein as revealed by ELISA. Furthermore, peptides F5(71-90) and F17(312-331) were demonstrated to agglutinate rabbit erythrocytes, and were mitogenic for BALB/c spleen cells but not thymocytes. These peptides enhanced the number of fimbria-specific antibody-secreting cells in BALB/c spleen cell cultures, and induced cytokines such as tumor necrosis factor-alpha and interleukin-6 production in human monocyte/macrophage cultures. The data demonstrate that these defined peptide segments are responsible for the immunostimulating portions within the fimbrial protein molecule.
 ...
PMID:Immunobiological activities of synthetic peptide segments of fimbrial protein from Porphyromonas gingivalis. 165 12

Communication circuits operating between activated monocytes/macrophages and adjacent hepatocytes in the liver effect important alterations in hepatocyte function. We demonstrate here that primary human hepatocytes and hepatoma cells are able to function as effector cells in the recruitment of inflammatory cells in hepatic disease and inflammatory states by synthesizing a neutrophil/lymphocyte chemotactic factor, interleukin-8. We have further investigated the possibility that endogenous factors elaborated by activated peripheral blood monocytes and Kupffer cells in the liver are mediators of hepatocyte-derived interleukin-8 expression. Twenty-four-hour conditioned medium from lipopolysaccharide-stimulated peripheral blood monocytes and nonparenchymal human liver cells enriched for Kupffer cells induced a time-dependent increase in interleukin-8 messenger RNA levels in SK-hepatoma cells over a 24-hr period, similar to that seen for tumor necrosis factor-alpha or interleukin-1 beta induction of interleukin-8 in primary hepatocytes. Exogenously added lipopolysaccharide or recombinant interleukin-6 had no effect. Cell-associated interleukin-8 antigen was present in SK-hepatoma and primary hepatocytes that had been incubated with macrophage-conditioned medium, tumor necrosis factor or interleukin-1 beta. Similarly, neutrophil chemotactic activity was secreted by SK-hepatoma cells, a significant proportion of which could be blocked with interleukin-8--specific antiserum. Preincubation of macrophage-conditioned medium with neutralizing antibodies to tumor necrosis factor-alpha or interleukin-1 beta reduced its interleukin-8 messenger RNA-inducing capacity. Exposure of SK-hepatoma to conditioned medium followed by removal of the stimulus resulted in a rapid down-regulation of interleukin-8 messenger RNA to 50% of the maximum level within the first hour. These data suggest that products derived from activated Kupffer cells can modulate hepatoma cells and primary hepatocyte interleukin-8 gene expression. In addition, macrophage/monocyte-derived tumor necrosis factor-alpha and interleukin-1 beta have major roles in the positive regulatory component of this modulation.
 ...
PMID:Kupffer cell-derived cytokines induce the synthesis of a leukocyte chemotactic peptide, interleukin-8, in human hepatoma and primary hepatocyte cultures. 166 18

The nature of the events that precipitate autoimmune diseases varies. Interleukin-1 and tumor necrosis factor do not precipitate autoimmune diseases but rather act as effector molecules. They induce eicosanoid and nitric oxide synthesis, stimulate collagenases and collagen synthesis, and trigger the genes for other cytokines, namely interleukin-2, interleukin-6 and interleukin-8. The ability to block interleukin-1 with the receptor antagonist, and tumor necrosis factor with soluble receptors, has given investigators specific tools to test the role of these two cytokines in the pathological processes of autoimmune disease.
 ...
PMID:Inflammatory cytokines: interleukin-1 and tumor necrosis factor as effector molecules in autoimmune diseases. 166 33

We have previously reported that synovial cells could participate in B cell differentiation processes in rheumatoid arthritis (RA) by producing interleukin-6 (IL-6) spontaneously or in response to interleukin-1 (IL-1) stimulation. In this paper, we examined the effects of tumor necrosis factor-alpha (TNF-alpha) on IL-6 production by human synovial fibroblasts. TNF-alpha, as well as IL-1, is a putative relevant molecule in the inflammatory process and in articular destruction in RA. Both IL-1 and TNF-alpha induced IL-6 production by synovial fibroblasts in a dose dependent manner. When synovial fibroblasts were stimulated by IL-1 and TNF-alpha in combination, IL-6 production increased synergistically after 48 hr of a 72 hr culture period. Kinetic studies revealed that the presence of both cytokines at the early phase of stimulation was required for the synergistic effect. These results suggest that TNF-alpha could be involved in a cytokine network in the affected joints of RA and could contribute synergistically with IL-1 to the IL-6 production by synovial fibroblasts in vivo.
 ...
PMID:Interleukin 1 and tumor necrosis factor-alpha synergistically increase the production of interleukin 6 in human synovial fibroblast. 166 42

There is clear evidence for communication between the immune and neuroendocrine systems. However, the effect of cytokines as major immune mediators on the hypothalamic growth peptides, GHRH and somatostatin (SRIH), is not well established. To investigate a possible hypothalamic action of the cytokines interleukin-1 beta (IL-1), interleukin-6, and tumor necrosis factor-alpha, on the release of GHRH and SRIH, we used a previously validated acute rat hypothalamic explant system. IL-1 caused a pronounced dose-dependent stimulation of SRIH in the dose-range 1-100 U/ml (P less than 0.01). GHRH showed a slight, but significant, increase in response to IL-1 tested in the dose-range 10-100 U/ml. Similar studies with mediobasal hypothalamic (GHRH and SRIH) or median eminence (SRIH) fragments produced no change in either GHRH or SRIH release. The effects of IL-1 were antagonized by the cyclo-oxygenase inhibitor, indomethacin (10 micrograms/ml). Stimulation of GHRH and SRIH could not be blocked by the CRH-antagonist alpha-helical CRH (9-41) at 10(-6) M. Interleukin-6, in the dose range 10-100 U/ml, and tumor necrosis factor-alpha, in the dose range 10-10,000 U/ml, had no effect on the acute hypothalamic release of either GHRH or SRIH. It is concluded that IL-1 stimulates the acute hypothalamic release of GHRH and SRIH, and that this effect is mediated by cyclo-oxygenase products. The marked IL-1 stimulation of hypothalamic SRIH release may override the minor increase of GHRH increase, and may thus contribute to disturbances in growth seen in the presence of chronic inflammation.
 ...
PMID:Interleukin-1 beta modulates the acute release of growth hormone-releasing hormone and somatostatin from rat hypothalamus in vitro, whereas tumor necrosis factor and interleukin-6 have no effect. 167 97

Heparin-binding growth factor-1 (HBGF-1), also known as acidic fibroblast growth factor, is a potent mitogen for a variety of cell types including vascular endothelial and smooth muscle cells. Studies using murine 3T3 fibroblasts have shown that HBGF-1 induces numerous cellular responses such as the tyrosine phosphorylation of specific polypeptides and the increased expression of actin mRNA. Here we report that the addition of HBGF-1 to quiescent human umbilical vein endothelial cells increases the level of platelet-derived growth factor (PDGF) A-chain mRNA but not PDGF B-chain mRNA. In contrast, factors that inhibit endothelial cell proliferation such as phorbol myristate acetate and the cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha increase both PDGF A-chain and B-chain mRNA levels. HBGF-1 induction of PDGF A-chain mRNA expression occurs in the presence of the protein synthesis inhibitor cycloheximide and thus does not require de novo protein synthesis. HBGF-1 also increases c-fos, c-jun, and c-myc mRNA levels; in the presence of cycloheximide, PDGF A-chain and protooncogene mRNA accumulation kinetics are similar. Nuclear run-on experiments indicate that the transcription rate of the PDGF A-chain gene transiently increases after HBGF-1 addition. Immunoprecipitation analysis using PDGF A-chain-specific antibodies indicates that HBGF-1-stimulated cells synthesize and secrete an increased amount of PDGF relative to unstimulated cells. If HBGF-1 can regulate PDGF expression by vascular endothelial cells in vivo, then HBGF-1 availability would be an important component of smooth muscle cell growth control. For example, HBGF-1 within the vessel wall would promote smooth muscle cell proliferation by (a) direct interaction with smooth muscle cell HBGF-1 receptors, and (b) increasing the amount of endothelial cell-derived PDGF available for binding to smooth muscle cell PDGF receptors.
 ...
PMID:Heparin-binding growth factor-1 stimulation of human endothelial cells induces platelet-derived growth factor A-chain gene expression. 168 99


<< Previous 1 2 3 4 5 6 7 8 9 10