Traces of bacterial lipopolysaccharide suppress IFN-gamma-induced nitric oxide synthase gene expression in primary mouse macrophages.

摘要: A nitric oxide synthase (iNOS) inducible by cytokines and microbial products contributes to the cytotoxic antimicrobial activity of mouse macrophages. Bacterial LPS interacts synergistically with IFN-gamma induce iNOS when both stimuli are added together. In contrast, we show here that pre-exposure peritoneal macrophages low concentrations suppresses induction is subsequently. Suppression required pretreatment for at least 8 h was optimal in range 50 200 pg/ml. exerted smooth rough forms from Escherichia coli lipid Salmonella minnesota, but not a biologically inactive Rhodobacter sphaeorides. nitrite accumulation enzyme prior exposure could be explained their markedly decreased content protein, as revealed immunoblot monospecific anti-iNOS IgG. Messenger RNA affected biphasic manner LPS. Five hours after addition IFN-gamma, mRNA levels were unaltered or even enhanced LPS, 24 48 h, expression inhibited strongly enough account reduced protein. did appear mediated endogenous prostaglandins, transforming growth factor-beta, TNF-alpha, though exogenous TNF-alpha also suppressive. These findings suggest preactivation pathways normally contributing synergistic may deplete factors needed its expression. Regulation vivo depend on relative tempo which inflammatory immune responses evolve.