Selenium inhibits lipopolysaccharide-induced nitric oxide production by attenuation of NF[kappa]B and p38 MAPK pathways in murine macrophages.
Kim-SH; Johnson-VJ; Sharma-RP
FASEB J 2003 Mar; 17(5)(Part 2):A1030
Selenium (Se) is an essential biological element that modulates a variety of cellular processes. In response to lipopolysaccharide (LPS) macrophages increase the production of nitric oxide (NO) and reactive oxygen species (ROS). These molecules cause pathophysiological conditions including many lethal diseases. The present study was designed to investigate the effect of Se on LPS-induced NO and ROS and the signaling pathways involved in a macrophage cell line, J774A.1. Pretreatment with Se decreased the production of NO in LPS-stimulated cells. Concomitant decrease in the expression of both mRNA and protein for inducible nitric oxide synthase (iNOS) was observed. Pretreatment of cells by Se decreased the LPS-induced nuclear translocation of nuclear factor-kappaB (NFkappaB) and this inhibition was reversed by addition of a dithiothreitol. Additionally, Se decreased the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) but not of JNK and ERK. Furthermore, Se decreased the intracellular reduced glutathione (GSH) and LPS-induced ROS. These data suggest that Se modulates the endotoxin-induced oxidative stress involving NFkappaB activation and p38 MAPK cascade in murine macrophages.
Cell-function; Cellular-function; Cellular-reactions; Pathology; Physiology; Physiological-disorders; Diseases; Oxidative-processes
Abstract; Conference/Symposia Proceedings
The FASEB Journal, Experimental Biology 2003, San Diego, California, April 11-15, 2003