Requirement for transcription factor IRF-1 in NO synthase induction in macrophages

R Kamijo, H Harada, T Matsuyama, M Bosland… - Science, 1994 - science.org
R Kamijo, H Harada, T Matsuyama, M Bosland, J Gerecitano, D Shapiro, J Le, SI Koh…
Science, 1994science.org
Production of nitric oxide (NO) by macrophages is important for the killing of intracellular
infectious agents. Interferon (IFN)-γ and lipopolysaccharide stimulate NO production by
transcriptionally up-regulating the inducible NO synthase (iNOS). Macrophages from mice
with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1-/-mice) produced
little or no NO and synthesized barely detectable iNOS messenger RNA in response to
stimulation. Two adjacent IRF-1 response elements were identified in the iNOS promoter …
Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents. Interferon (IFN)- γ and lipopolysaccharide stimulate NO production by transcriptionally up-regulating the inducible NO synthase (iNOS). Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1-/- mice) produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation. Two adjacent IRF-1 response elements were identified in the iNOS promoter. Infection with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type mice. Thus, IRF-1 is essential for iNOS activation in murine macrophages.
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