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 mediators nitric oxide (NO) and IL-6 was examined in murine embryonic fibroblasts. 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, their STAT1-deficient counterparts failed to synthesise detectable levels of this free radical gas. Inability of STAT1-/- fibroblasts to produce NO was accompanied by complete absence of mRNA for iNOS and its transcription factor 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 induction of iNOS, but not IL-6 in murine fibroblasts.
Samardzic
T
T
Institute for Biological Research "Sinisa Stankovic", Belgrade, Yugoslavia. svelja@eunet.yu
Jankovic
V
V
Stosic-Grujicic
S
S
Trajkovic
V
V
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D005347:Fibroblasts / Q000201:enzymology* / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse