Requirement for Transcription Factor IRF-1 in NO Synthase Induction in Macrophages
- 18 March 1994
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 263 (5153), 1612-1615
- https://doi.org/10.1126/science.7510419
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.Keywords
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