LPS and TNF alpha induce SOCS3 mRNA and inhibit IL-6-induced activation ofSTAT3 in macrophages

Recent findings indicate that cytokine signaling can be modulated by other mediators of simultaneously activated signal transduction pathways. In this study we show that LPS and TNF alpha are potent inhibitors of IL-6-mediate d STAT3 activation in human monocyte derived macrophages, rat liver macroph ages and RAW 264.7 mouse macrophages but not in human hepatoma cells (HepG2 ) or in rat hepatocytes. Accordingly, LPS and TNF alpha were found to induc e the expression of SOCS3 mRNA in each of the investigated type of macropha ges but not in HepG2 cells. Using a specific inhibitor, evidence is present ed that the p38 MAP kinase might be involved, especially for the inhibitory effect of TNF alpha. (C) 1999 Federation of European Biochemical Societies .