Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter
Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter
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DOI：
10.4049/jimmunol.170.2.997
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发表时间：
2003-01-15
影响因子：
4.4
通讯作者：
Asano, Y
中科院分区：
文献类型：
--
作者：
Maruyama, S;Sumita, K;Asano, Y
IL-12是由p40和p35组成的异源二聚体，是保护宿主免受病毒和微生物感染的关键细胞因子。IL-12在感染过程中连接先天免疫系统和获得性免疫系统，诱导1型T细胞的分化，在消灭微生物中发挥重要作用。在ifn - γ存在的情况下，NF-kappaB调节il - 12p40基因的诱导。IFN- γ诱导IFN调节因子-1 (IRF-1)，进而诱导il - 12p40基因的转录。然而，IRF-1在il - 12p40基因启动子区域的结合位点尚未正式确定。在本研究中，我们证明了IRF-1直接结合到il - 12p40基因启动子上，并确定了其结合位点。il - 12p40基因启动子区域的IRF-1结合位点位于5′上游区域的-72 ~ -58区域。-63 ~ -61位点是IRF-1结合il - 12p40基因启动子的关键位点。虽然ifn - γ必须存在才能诱导IL-12 p40基因，但p35基因可以被LPS强烈诱导，即使在没有ifn - γ的情况下，因此p35基因的诱导是独立于IRF-1的。
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.