Requirement for Transcription Factor IRF-1 in NO Synthase Induction in Macrophages
Ryutaro Kamijo(University Medical Center), Hisashi Harada(The University of Osaka), T. Matsuyama(Ontario Institute for Cancer Research), Maarten C. Bosland(Columbia University Irving Medical Center), John F. Gerecitano(University Medical Center), Daniel Shapiro(University Medical Center), Junming Le(University Medical Center), S. I. Koh(The University of Osaka), Tohru Kimura(The University of Osaka), Shawn J. Green(CASI Pharmaceuticals (United States)), Tak W. Mak(Ontario Institute for Cancer Research), Tadatsugu Taniguchi(The University of Osaka), J Vilček(University Medical Center)
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Abstract
Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents. Interferon (IFN)-gamma 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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