Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter

被引:61
|
作者
Maruyama, S
Sumita, K
Shen, H
Kanoh, M
Xu, X
Sato, M
Matsumoto, M
Shinomiya, H
Asano, Y [1 ]
机构
[1] Ehime Univ, Sch Med, Dept Immunol & Host Def, Shigenobu, Ehime 7910295, Japan
[2] Univ Tokyo, Grad Sch Med, Dept Immunol, Tokyo, Japan
来源
JOURNAL OF IMMUNOLOGY | 2003年 / 170卷 / 02期
关键词
D O I
10.4049/jimmunol.170.2.997
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-12 is a heterodimer composed of p40 and p35 and is a key cytokine that functions to protect the host from viral and microbial infections. IL-12 links the innate immune system with the acquired immune system during infection, and induces differentiation of type 1 T cells that play an important role in the eradication of microbes. The induction of the IL-12 p40 gene is regulated by NF-kappaB in the presence of IFN-gamma. IFN-gamma induces IFN regulatory factor-1 (IRF-1), which in turn induces the transcription of the IL-12 p40 gene. However, the IRF-1 binding site in the promoter region of the IL-12 p40 gene has not yet been formally determined. In the present study, we demonstrated that IRF-1 directly bind's to the IL-12 p40 gene promoter and identified its binding site. The IRF-1 binding site in the promoter region of the IL-12 p40 gene is shown to be in the -72 to -58 area of the 5'-upstream region. The -63 to -61 position is the critical site within this region for the binding of IRF-1 to the IL-12 p40 gene promoter. While IFN-gamma must be present for IL-12 p40 gene induction, the p35 gene is strongly induced by LPS, even in the absence of IFN-gamma, and therefore the induction of the p35 gene is IRF-1 independent.
引用
收藏
页码:997 / 1001
页数:5
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