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

FEBS Letters

Tamaoki, Satoshi³  Komuro, Katsutoshi³  Wang, I-Ming¹  Ozato, Keiko²  Masumi, Atsuko³ 

[1] Respiratory Diseases, Wyeth Research, Cambridge, MA 02140, USA;Laboratory of Molecular Growth Regulation, NICHD, National Institutes of Health, Bethesda, MD 20892, USA;Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo 208-0011, Japan

关键词: Interleukin-12;    ICSBP;    IRF-1;    Mouse macrophage;    ISRE;    IFN-γ;    ICSBP;    interferon consensus sequence binding protein;    IRF-1;    interferon regulatory factor-1;    IFN-γ;    interferon-γ;    IL-12;    interleukin-12;    ISRE;    interferon stimulated responsive element;   

DOI  :  10.1016/S0014-5793(02)03556-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

IRF-8/ICSBP and IRF-1 are IRF family members whose expression is induced in response to IFN-γ in macrophages. IL-12 is a cytokine produced in macrophages that plays a critical role in host defense. IFN-γ 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-γ/LPS. Mutation of the Ets or NFκB 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 NFκB 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.

【 授权许可】

Unknown