REQUIREMENT FOR TRANSCRIPTION FACTOR IRF-1 IN NO SYNTHASE INDUCTION IN MACROPHAGES

被引:784
作者
KAMIJO, R
HARADA, H
MATSUYAMA, T
BOSLAND, M
GERECITANO, J
SHAPIRO, D
LE, J
KOH, SI
KIMURA, T
GREEN, SJ
MAK, TW
TANIGUCHI, T
VILCEK, J
机构
[1] NYU MED CTR,DEPT MICROBIOL,NEW YORK,NY 10016
[2] NYU MED CTR,KAPLAN CANC CTR,NEW YORK,NY 10016
[3] OSAKA UNIV,INST MOLEC & CELLULAR BIOL,OSAKA 565,JAPAN
[4] UNIV TORONTO,PRINCESS MARGARET HOSP,ONTARIO CANC INST,DEPT MED BIOPHYS,TORONTO M4X 1K9,ON,CANADA
[5] UNIV TORONTO,PRINCESS MARGARET HOSP,ONTARIO CANC INST,DEPT IMMUNOL,TORONTO M4X 1K9,ON,CANADA
[6] NYU MED CTR,INST ENVIRONM MED,TUXEDO PK,NY 10987
[7] NYU MED CTR,KAPLAN CANC CTR,TUXEDO PK,NY
[8] ENTREMED INC,ROCKVILLE,MD 20850
关键词
D O I
10.1126/science.7510419
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页码:1612 / 1615
页数:4
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