Requirement for Transcription Factor IRF-1 in NO Synthase Induction in Macrophages

作者：Ryutaro Kamijo, Hisashi Harada, T. Matsuyama, Maarten C. Bosland, John F. Gerecitano, Daniel Shapiro, Junming Le, S. I. Koh, Tohru Kimura, Shawn J. Green, Tak W. Mak, Tadatsugu Taniguchi, J Vilček · 发表于：Science · 年份：1994 · DOI：10.1126/science.7510419 · 被引用次数：846 · 研究领域：Immune Response and Inflammation、Nitric Oxide and Endothelin Effects、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

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.