IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages

被引:73
作者
Masumi, A
Tamaoki, S
Wang, IM
Ozato, K
Komuro, K
机构
[1] Natl Inst Infect Dis, Dept Safety Res Biol, Tokyo 2080011, Japan
[2] Showa Univ, Sch Med, Dept Biochem, Shinagawa Ku, Hatanodia, Japan
[3] Wyeth Res, Resp Dis, Cambridge, MA 02140 USA
[4] NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA
关键词
interleukin-12; ICSBP; IRF-1; mouse macrophage; ISRE; IFN-gamma;
D O I
10.1016/S0014-5793(02)03556-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
IRF-8/ICSBP and IRF-1 are IRF family members whose expression is induced in response to IFN-gamma in macrophages. IL-12 is a cytokine produced in macrophages that plays a critical role in host defense. IFN-gamma and bacterial lipopolysaccharide (LPS) induce IL-12p40 transcription, which is necessary for the production of IL-12. We have previously shown that IL-12p40 expression is impaired in ICSBP-deficient mice and that transfection of ICSBP together with IRF-1 can activate IL-12p40 expression in mouse macrophage cells. To further study the role of ICSBP and IRF-1, we investigated murine IL-12p40 promoter activity in the macrophage cell line RAW 264.7. We show here that co-transfection of ICSBP and IRF-1 synergistically stimulates IL-12 promoter activity to a level comparable to that induced by IFN-gamma/LPS. Mutation of the Ets or NFkappaB site previously shown to be important for IL-12p40 transcription did not abolish the activation by ICSBP and IRF-1. However, mutation of the ISRE-like site found downstream from the NFkappaB and C/EBP sites abrogated the activation by ICSBP and IRF-1. Together, these results indicate that ICSBP and IRF-1 cooperatively stimulate murine IL-12 transcription through a novel regulatory element in the murine promoter. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:348 / 353
页数:6
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