IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages
IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages
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DOI：
10.1016/s0014-5793(02)03556-1
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发表时间：
2002-11-06
期刊：
影响因子：
3.5
通讯作者：
Komuro, K
中科院分区：
文献类型：
--
作者：
Masumi, A;Tamaoki, S;Komuro, K
IRF-8/ICSBP和IRF-1是IRF家族成员，其表达响应于巨噬细胞中的IFN-γ而被诱导。IL-12是在巨噬细胞中产生的细胞因子，其在宿主防御中起关键作用。IFN-γ和细菌脂多糖（LPS）诱导IL-12 p40转录，这是产生IL-12所必需的。我们先前已经表明，IL-12 p40表达受损ICSBP缺陷小鼠和ICSBP与IRF-1一起转染可以激活小鼠巨噬细胞中的IL-12 p40表达。为了进一步研究ICSBP和IRF-1的作用，我们研究了巨噬细胞系RAW 264.7中的鼠IL-12 p40启动子活性。我们在这里表明，ICSBP和IRF-1的共转染协同刺激IL-12启动子活性的水平相当的IFN-γ/LPS诱导。Ets或NF κ B位点的突变以前被证明对IL-12 p40转录很重要，但没有消除ICSBP和IRF-1的激活。然而，在NF κ B和C/EBP位点下游发现的ISRE样位点的突变废除了ICSBP和IRF-1的激活。总之，这些结果表明，ICSBP和IRF-1协同刺激鼠IL-12的转录，通过一种新的调节元件在鼠启动子。(C)2002年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
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.