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)

High levels of interleukin-6 (IL-6) have been detected in synovial fluid from patients with inflammatory arthropathies associated with local bone resorption, suggesting a role for IL-6 as a local regulator of bone resorption and remodeling. In the present study we examined the effects of IL-6 on [3H]thymidine ([3H]TdR) incorporation, collagen synthesis, and alkaline phosphatase activity in UMR-106-01 rat osteoblastic osteosarcoma cells. IL-6 stimulated a dose-dependent increase in [3H]TdR incorporation that was maximal at 1000 U/ml (-147% of basal, p less than 0.005) in osteoblastlike cells that were in a logarithmic phase of growth. The increase in [3H]TdR incorporation was maximal between 12 and 24 h and was neutralized by pretreatment with the polyclonal rabbit antibody to IL-6. IL-6 also increased cell number and the secretion of prostaglandin E2 in UMR-106-01 cells in logarithmic growth phase. The stimulation of [3H]TdR incorporation and release of PGE2 into the culture medium by IL-6 was inhibited by indomethacin. A 24 h exposure of the osteoblastlike cells to 1000 U/ml of IL-6 reduced [3H]proline incorporation into collagenase-digestible (CDP) protein to 73% of control values (p less than 0.01). Noncollagen protein (NCP) synthesis was inhibited to 80% of control values (p less than 0.01) by 1000 U/ml of IL-6. The inhibitory effect was relatively greater on CDP than on NCP and consequently resulted in a decrease in the percentage of collagen synthesis. Alkaline phosphatase activity was not altered in these cells after a 24 h exposure to 1-1000 U/ml of IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of interleukin-6 on cellular function in UMR-106-01 osteoblastlike cells. 202 35

Phosphatidic acid (PA) is a phospholipid involved in signal transduction and in glycerolipid biosynthesis. CDP-diacylglycerol synthase (CDS) or CTP:phosphatidate cytidylyltransferase (EC 2.7.7.41) catalyzes the conversion of PA to CDP-diacylglycerol (CDP-DAG), an important precursor for the synthesis of phosphatidylinositol, phosphatidylglycerol, and cardiolipin. We describe in this study the isolation and characterization of a human cDNA clone that encodes amino acid sequences homologous to Escherichia coli, yeast, and Drosophila CDS sequences. Expression of this human cDNA under the control of a GAL1 promoter in a null cds1 mutant yeast strain complements its growth defect and produces CDS activity when induced with galactose. Transfection of this cDNA into mammalian cells leads to increased CDS activity in cell-free extracts using an in vitro assay that measures the conversion of [alpha-32P]CTP to [32P]CDP-DAG. This increase in CDS activity also leads to increased secretion of tumor necrosis factor-alpha and interleukin-6 from endothelial ECV304 cells upon stimulation with interleukin-1beta, suggesting that CDS overexpression may amplify cellular signaling responses from cytokines.
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PMID:Isolation and expression of an isoform of human CDP-diacylglycerol synthase cDNA. 911 37

Recent controlled and uncontrolled trial data in inflammatory bowel disease have suggested several new avenues of possible therapies and refined our understanding of the uses and selectiveness of anti-tumor necrosis factor (TNF)-based therapies. Infliximab remains the only proven effective anti-TNF therapy, whereas others have proven ineffective (etanercept, CDP-571) or of limited utility (thalidomide, CDP-870). A Crohn's disease Clinical trial Evaluating infliximab in a New long-term Treatment regimen (ACCENT I) and ACCENT II trials supported the strategy of using 5 to 10 mg/kg of infliximab on an every 8-week basis for maintenance of remission, although in clinical practice many physicians take variable approaches to maintenance of remission dosing schedules. On the other hand, no controlled trial data to date have supported the use of infliximab in ulcerative colitis. Therapies utilizing novel mechanistic approaches, such as hematopoietic growth factors, mitogen-activated protein (MAP)-kinase inhibition, and peroxisome proliferator activated receptor gamma ligand receptor binding have shown promise in small uncontrolled trials and await confirmation of their utility in randomized, placebo-controlled trials. Newer biologic (natalizumab) or cytokine-based therapies (monoclonal antibody to interleukin-6) have shown preliminary evidence of efficacy in controlled trials, but neither have yet been approved by the US Food and Drug Administration and, therefore, have not been commercialized. However, tacrolimus, a potent calcineurin inhibitor and inhibitor of interleukin-2 expression, has shown efficacy in Crohn's disease, albeit at the cost of substantial potential toxicity.
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PMID:Newer Therapies for Inflammatory Bowel Disease. 1514 78