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 effects of SM-8849 on the development of autoimmune disease in MRL/Mp-1pr/1pr mice were examined. SM-8849 improved survival as well as renal disease, restored the deficits in splenic cell responsiveness to stimulation by mitogens or conventional antigens, and prevented lymphadenopathy and splenomegaly coincident with a decrease in the number of Thy-1+/Lyt-2-/L3T4- cells. SM-8849 also suppressed the production of the B-cell differentiation factor, possibly with a resulting preferential reduction of autoantibodies. In addition, SM-8849 depressed the production of hydrogen peroxide from macrophages. These results suggest that the administration of SM-8849 to a subject with autoimmune diseases can induce immunological improvements with possible clinical effectiveness.
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PMID:Alteration in progression of murine autoimmune disease by treatment with a novel immunomodulator, SM-8849. 178 57

Addition of recombinant interleukin-6 (IL-6) to Plasmodium yoelii hepatic cultures resulted in a specific dose-dependent inhibition of parasite development. Time course experiments showed that, without any direct effect on free sporozoites, IL-6 exerts its action during both the early phase of infection and during the subsequent maturation of the schizonts. Elicitation of the oxidative burst appears to be one mechanism by which IL-6 interferes with the development of hepatic phase. Catalase and superoxide dismutase, two scavengers of hydrogen peroxide and superoxide anions, reversed the IL-6 mediated parasiticidal activity.
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PMID:Inhibitory activity of IL-6 on malaria hepatic stages. 205 7

We have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) and three cytokines on expression of antioxidative enzymes, manganese-superoxide dismutase, copper, zinc-superoxide dismutase, and catalase in cultured hepatocytes of rat. While interleukin-1 beta and interleukin-6 induced manganese-superoxide dismutase gene expression, they slightly suppressed catalase gene expression in rat hepatocytes. TGF-beta 1 suppressed expression of all these antioxidative enzymes in time- and cell density-dependent manners. Furthermore, we examined the effect of TGF-beta 1 on expression of glutathione peroxidase and glutathione-S-transferase, which exhibit glutathione-dependent peroxidase activity in rat hepatocytes. Expression of two major classes of the rat glutathione-S-transferase subunits 1 and 2 was also reduced by TGF-beta 1, although expression of glutathione peroxidase was not affected. Flow cytometric analysis indicated that production of peroxides was increased in hepatocytes treated with TGF-beta 1. These data suggest that augmented production of hydrogen peroxide and its intermediate through suppression of antioxidative enzyme expression may participate in cellular injury or growth inhibition promoted by TGF-beta 1.
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PMID:Suppression of antioxidative enzyme expression by transforming growth factor-beta 1 in rat hepatocytes. 751 58

In the present study, the distal part of the 5'-flanking region of the rainbow trout metallothionein-A promoter was sequenced in order to identify cis-acting regulatory elements. Analysis of this sequence combined with that previously reported for the 5'-flanking region directly proximal to the start of transcription revealed several putative regulatory sequences. In total, six metal-responsive elements (MREs) were identified; these sequences were organised into two clusters, one containing two copies of MRE and located close to the predicted TATA box sequence, and a second consisting of four MREs and lying 500-700 bp upstream from the start of transcription. In addition, the 5'-flanking region contained sequences sharing high similarity with the activator protein 1 consensus sequence as well as one nuclear-factor-interleukin-6-responsive element. Functional analysis of the promoter was performed by introducing deletion mutants of the 5'-flanking region into the vector pGL-2, directly upstream from the luciferase reporter gene. Both MRE clusters were needed for maximal metal inducibility in both rainbow trout hepatoma (RTH-149) and human hepatoblastoma (Hep G2) cell lines. Furthermore, the distal region was found to be functional in promoting gene transcription following exposure of RTH-149 cells to hydrogen peroxide.
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PMID:Structural and functional analysis of the rainbow trout (Oncorhyncus mykiss) metallothionein-A gene. 760 Nov 21

A transformed bovine peritoneal macrophage cell line was developed and characterized. Primary peritoneal macrophages were transformed by calcium-phosphate transfection with SV40 plasmid DNA. The transformed cell line retained the morphology of resident peritoneal macrophages as determined by light microscopy and histochemical analysis showed non-specific esterase activity. In addition, immunohistochemical staining of transformed peritoneal macrophages for lysozyme activity was positive. Transformed cells phagocytized Staphylococcus aureus, lysed chicken red blood cell (RBC) targets with and without opsonization and produced hydrogen peroxide radicals and interleukin-6 upon stimulation with opsonized zymosan and lipopolysaccharide, respectively. Transformed cells were also able to ingest and kill Mycobacterium paratuberculosis, an acid-fast bacillus. These results suggest that this cell line should be useful to study interactions between the bovine and intracellular pathogens.
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PMID:Immortalization and characterization of bovine peritoneal macrophages transfected with SV40 plasmid DNA. 767 7

This study investigated the effects of feeding mice lipids with different fatty acid compositions upon the ability of stimulated macrophages to produce inflammatory mediators. Weanling mice were fed for 8 weeks on a low-fat (LF; 2.5% by weight) diet or on diets containing 20% by weight of hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), or menhaden (fish) oil (MO). Thioglycollate-elicited peritoneal macrophages were isolated. Macrophages isolated from MO-fed mice produced less PGE2, 6-keto-PGF1 alpha, TXB2, and interleukin-6 in response to lipopolysaccharide (LPS) stimulation than those from mice fed each of the other diets. Macrophages from mice fed the OO, SO, or MO diets produced less tumor necrosis factor alpha in response to LPS stimulation than those from mice fed the LF or HCO diets. There was no effect of dietary lipid manipulation upon the production of interleukin-1 by LPS-stimulated macrophages. Macrophages from mice fed the MO diet produced more superoxide and hydrogen peroxide in response to phorbol ester stimulation than those from mice fed each of the other diets. In response to unopsonized zymosan, macrophages from mice fed the SO or MO diets produced more hydrogen peroxide than macrophages from mice fed the other diets. LPS-stimulated nitric oxide production was greater from macrophages from OO-, SO-, or MO-fed mice than from those fed the LF or HCO diets. Thus, the nature of the lipid consumed in the diet has significant effects upon the production of a variety of inflammatory mediators by macrophages. The most potent effect is caused by fish oil consumption. Possible mechanisms by which dietary fatty acids, particularly the n-3 polyunsaturated fatty acids found in fish oils, could affect mediator production by macrophages are described. The clinical relevance of such effects is discussed.
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PMID:Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. 775 22

Redox-based modulation plays a role in transcriptional control of gene expression. In the present study, we investigated the possible role of reactive oxygen species in the induction of interleukin-6 (IL-6) mRNA and in increases in NF kappa B binding activity by tumor necrosis factor (TNF) alpha using a mouse fibroblastic cell line, Balb/3T3. Expression of IL-6 mRNA is known to be dependent upon NF kappa B that binds to the 5'-flanking region of the IL-6 gene. We found that: (i) TNF alpha increased IL-6 mRNA levels and this increase was inhibited by N-acetyl-L-cysteine (NAC), a scavenger of reactive oxygen species. (ii) NF kappa B binding activity in this cell line was also increased by TNF alpha, and the increase was inhibited in the presence of NAC. (iii) The treatment of cells with low doses of hydrogen peroxide increased the NF kappa B binding activity. (iv) Expression of a reporter gene in which the chloramphenicol acetyltransferase (CAT) gene was under the control of NF kappa B binding sites was induced by hydrogen peroxide. These results suggest that the induction of IL-6 mRNA is regulated by a mechanism involving reactive oxygen species and that NF kappa B, whose activity is sensitive to the cellular redox state, plays an important role in this induction in a fibroblastic cell line, Balb/3T3, stimulated with TNF alpha.
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PMID:Inhibition by N-acetyl-L-cysteine of interleukin-6 mRNA induction and activation of NF kappa B by tumor necrosis factor alpha in a mouse fibroblastic cell line, Balb/3T3. 792 24

Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are major proinflammatory cytokines inducing the synthesis and release of many inflammatory mediators. They are involved in immune regulation, autoimmune diseases, and inflammation. Acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum. When human monocytes/macrophages stimulated with silica were treated with 0.1-10 microg/ml acanthoic acid, the production of IL-1 and TNF-alpha was inhibited up to 90%, but the production of interleukin-6 (IL-6) was not inhibited at all. At these concentrations, it had no cytotoxic effect on human monocytes/macrophages. It also suppressed the production of TNF-alpha by alveolar macrophages and lymphocytes stimulated with silica. In addition, acanthoic acid inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages and neutrophils. To know the antifibrotic effects of acanthoic acid, its effects on fibroblast proliferation and collagen synthesis were tested. The proliferation of NIH3T3 cells was inhibited almost completely by the addition of the culture supernatants of human monocytes/macrophages treated with acanthoic acid, but not by the addition of acanthoic acid only. In vitro and in vivo treatment with acanthoic acid reduced collagen production by rat lung fibroblasts and lung tissue. Furthermore, acanthoic acid suppressed granuloma formation and fibrosis in the experimental silicosis. Acanthoic acid reduced serum GOT and GPT in the rats with cirrhosis induced by CCl4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that acanthoic acid has a potent anti-inflammatory and antifibrosis effect by reducing IL-1 and TNF-alpha production.
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PMID:Suppression of interleukin-1 and tumor necrosis factor-alpha production by acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, and it antifibrotic effects in vivo. 866 Aug 20

Essentially complete backbone and side-chain 1H, 15N and 13C resonance assignments for the 185-amino-acid cytokine interleukin-6 (IL-6) are presented. NMR experiments were performed on uniformly [15N]- and [15N,13C]-labeled recombinant human IL-6 (rIL-6) using a variety of heteronuclear NMR experiments. A combination of 13C-chemical shift, amide hydrogen-bond exchange, and 15N-edited NOESY data allowed for analysis of the secondary structure of IL-6. The observed secondary structure of IL-6 is composed of loop regions connecting five alpha-helices, four of which are consistent in their length and disposition with the four-helix bundle motif present in other related cytokines and previously postulated for IL-6. In addition, the topology of the overall fold was found to be consistent with a left-handed up-up-down-down four-helix bundle based on a number of long-range interhelical NOEs. The results presented here provide deeper insight into structure-function relationships among members of the four-helix bundle family of proteins.
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PMID:Complete 1H, 15N and 13C assignments, secondary structure, and topology of recombinant human interleukin-6. 891 71

Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ob mice, which have a mutation that causes leptin deficiency, proving the importance of this factor and its receptors in the obesity syndrome. Cells with leptin receptors have been identified outside of the appetite regulatory centers in the brain. Thus leptin has peripheral targets. Because macrophages express signaling-competent leptin receptors, these cells may be altered during chronic leptin deficiency. Consistent with this concept, the present study identifies several phenotypic abnormalities in macrophages from ob/ob mice, including decreased steady-state levels of uncoupling protein-2 mRNA, increased mitochondrial production of superoxide and hydrogen peroxide, constitutive activation of CCAAT enhancer binding protein (C/EBP)-beta, an oxidant-sensitive transcription factor, increased expression of interleukin-6 and cyclooxygenase (COX)-2, two C/EBP-beta target genes, and increased COX-2-dependent production of PGE2. Given the importance of macrophages in the general regulation of inflammation and immunity, these alterations in macrophage function may contribute to obesity-related pathophysiology.
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PMID:Phenotypic abnormalities in macrophages from leptin-deficient, obese mice. 995 Jul 66


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