Publication Date:
1994-03-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kamijo, R -- Harada, H -- Matsuyama, T -- Bosland, M -- Gerecitano, J -- Shapiro, D -- Le, J -- Koh, S I -- Kimura, T -- Green, S J -- A128993/PHS HHS/ -- P30CA13343/CA/NCI NIH HHS/ -- R35CA49731/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1994 Mar 18;263(5153):1612-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, New York University Medical Center, NY 10016.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7510419" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Oxidoreductases/*biosynthesis/genetics
;
Animals
;
Base Sequence
;
DNA-Binding Proteins/genetics/*metabolism
;
Enzyme Induction
;
Interferon Regulatory Factor-1
;
Interferons/pharmacology
;
Lipopolysaccharides/pharmacology
;
Macrophage Activation
;
Macrophages, Peritoneal/*enzymology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Inbred DBA
;
Molecular Sequence Data
;
Mutation
;
Mycobacterium bovis
;
Nitric Oxide/metabolism
;
Nitric Oxide Synthase
;
Phosphoproteins/genetics/*metabolism
;
Promoter Regions, Genetic
;
RNA, Messenger/genetics/metabolism
;
Regulatory Sequences, Nucleic Acid
;
Transcription Factors/genetics/*metabolism
;
Tuberculosis/immunology
;
Tumor Necrosis Factor-alpha/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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