STAT1 is required for iNOS activation, but not IL-6 production in murine fibroblasts

The role of transcription factor STAT1 in production of pro-inflammatory me diators nitric oxide (NO) and IL-6 was examined in murine embryonic fibrobl asts. While cells from wild-type animals released large amounts of NO after stimulation with IFN-gamma in combination with LPS, TNF-alpha or IL-1, the ir STAT1-deficient counterparts failed to synthesise detectable levels of t his free radical gas. Inability of STAT1(-/-) fibroblasts to produce NO was accompanied by complete absence of mRNA for iNOS and its transcription fac tor IRF-1, both readily upregulated in wild-type cells. However, treatment with cytokines (IFN-gamma, TNF-alpha, IL-1, IL-17) significantly increased IL-6 generation in STAT1-deficient fibroblasts. These results indicate that STAT1 activation and subsequent IRF-1 transcription are required for induc tion of iNOS, but not IL-6 in murine fibroblasts. (C) 2001 Academic Press.