Taurine chloramine inhibits the LPS-induced NO production by modulating Ras-MEK-ERK signaling pathway and NFkB

초록

Taurine is an abundant free amino acid in inflammatory cells and protects cells from inflammatory damages. Taurine reacts with toxic hypochlorous acid (HOCl/OCl-) produced by the myeloperoxidase system and generates less toxic taurine chloramine (Tau-Cl) in neutrophils. Tau-Cl inhibits nitric oxide (NO) production in macrophages stimulated with lipopolysaccharide (LPS) and interferon-g. In this study, we investigated the mechanism(s) which Tau-Cl inhibits LPS-induced NO production in macrophages. Tau-Cl significantly inhibited LPS-derived iNOS expression and NO production in RAW 264.7 cells. Tau-Cl inhibited LPS-induced extracellular signal-regulated kinase (ERK)1/2 activation in a dose-dependent manner, while it had no effect on p38 MAPK activation. Tau-Cl also inhibited Ras activation and MAP/ERK kinase (MEK)1/2 activation. These results suggest that Tau-Cl suppresses the LPS-induced NO production by inhibiting Ras-MEK-ERK signaling pathway, not by its direct cytotoxicity. In addition, Tau-Cl selectively inhibited nuclear factor kappaB (NF-kB) activation without affecting activator protein 1 (AP-1). Accordingly, the present results suggest that Tau-Cl protects cells from inflammatory injury resulting from overproduction of NO by a signaling-specific manner.