Requirement for transcription factor IRF-1 in NO synthase induction in macrophages.
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.
Kamijo
R
R
Department of Microbiology, New York University Medical Center, NY 10016.
Harada
H
H
Matsuyama
T
T
Bosland
M
M
Gerecitano
J
J
Shapiro
D
D
Le
J
J
Koh
S I
SI
Kimura
T
T
Green
S J
SJ
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009154:Mutation; D009163:Mycobacterium bovis; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D008070:Lipopolysaccharides; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007372:Interferons; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases