Taurine chloramine inhibits production of nitric oxide and prostaglandin E2 in activated C6 glioma cells by suppressing inducible nitric oxide synthase and cyclooxygenase-2 expression.
Taurine prevents tissue damage in various models of inflammation through a mechanism postulated to involve taurine monochloramine (Tau-Cl). Tau-Cl is formed through the action of a halide-dependent myeloperoxidase system associated with polymorphonuclear leukocytes (PMN), eosinophils, and basophils. Production of nitric oxide (NO), PGE2, and other proinflammatory mediators by activated macrophages is inhibited by Tau-Cl. Since glial cells may be activated to produce NO, PGE2 and other proinflammatory mediators, similar to macrophages, we examined the effects of Tau-Cl on the production of NO and PGE2 by rat C6 glioma cells. C6 cells were seeded to grow over 2-3 days to approximately 90% confluency before exposure to various concentrations of Tau-Cl in HBSS for 2 h (37 degreesC, 5% CO2). The HBSS was replaced, after washing the cells, with DMEM containing 4% fetal calf serum and activators (LPS, 10 microgram/ml; rat rIFN-gamma, 50 U/ml; and human rTNF-alpha, 50 ng/ml). Media content of NO2- and PGE2 was measured 48 h after activation and cell lysates were subjected to SDS-PAGE followed by Western blot analyses to determine the relative expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. Media accumulation of NO2- and PGE2 was inhibited by Tau-Cl in a concentration dependent manner and this was accompanied by decreased amounts of iNOS and COX-2 proteins in cell lysates. Additional experiments determined the effects of Tau-Cl on the kinetics of iNOS and COX-2 mRNA expression. Expression of iNOS mRNA was markedly inhibited in activated C6 cells that were previously exposed to Tau-Cl and this persisted for at least 24 h. In contrast, inhibition of COX-2 mRNA expression was only transiently reduced in Tau-Cl exposed cells during the first 4 h of activation and was relatively unimpaired thereafter (8-24 h). These results suggest that Tau-Cl inhibits the transcriptional expression of the iNOS gene but inhibits expression of COX-2 protein by post-transcriptional mechanisms.
Liu
Y
Y
Departments of Developmental Biochemistry and Immunology, New York State Institute for Basic Research, 1050 Forest Hill Road, Staten Island, NY, 10314-6330, USA.
Tonna-DeMasi
M
M
Park
E
E
Schuller-Levis
G
G
Quinn
M R
MR
D000818:Animals; D015152:Blotting, Northern; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D005910:Glioma; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D018836:Inflammation Mediators; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D013654:Taurine; D009569:Nitric Oxide; C043410:N-chlorotaurine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone