Inhibition of LPS-induced NO production by taurine chloramine in macrophages is mediated though Ras-ERK-NF-kappaB.
Taurine is an abundant free amino acid in inflammatory cells that protects cells from inflammatory damages. Although the protection mechanism remains unclear, taurine chloramine (Tau-Cl) produced by the reaction between taurine and hypochlorous acid in neutrophils plays an important role. In this study, we investigated the mechanism(s) by which Tau-Cl inhibits LPS-induced NO production in macrophages. Tau-Cl inhibited LPS-induced iNOS expression and NO production in RAW 264.7 cells. LPS treatment elevated the level of active Ras-GTP, and Tau-Cl inhibited LPS-induced Ras activation. Tau-Cl also inhibited ERK1/2 activation in a dose-dependent manner in both RAW 264.7 cells and murine peritoneal macrophages, whereas it did not exert any effect on p38 MAPK activation. Furthermore, Tau-Cl inhibited NF-kappaB activation without affecting AP-1 activity. These results suggest that Tau-Cl suppresses LPS-induced NO production by inhibiting specific signaling pathways. Thus, Tau-Cl protects cells from inflammatory injury resulting from overproduction of NO in a signaling pathway-specific manner.
Kim
Jun Woo
JW
Inha University College of Medicine, 7-206 3rd St., Shinheung-dong, Jung-gu, Incheon 400-712, Republic of Korea.
Kim
Chaekyun
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004247:DNA / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D018631:ras Proteins / Q000502:physiology*
D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D013654:Taurine; D009569:Nitric Oxide; C043410:N-chlorotaurine; D004247:DNA; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins