Nakamura Megumi, Hamada Michito, Hasegawa Kazuteru, Kusakabe Manabu, Suzuki Hirona, Greaves David R, Moriguchi Takashi, Kudo Takashi, Takahashi Satoru
Department of Anatomy and Embryology, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences and Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
Gene. 2009 Sep 15;445(1-2):66-72. doi: 10.1016/j.gene.2009.06.003. Epub 2009 Jun 17.
c-Maf, which is one of the large Maf transcription factors, can bind to Maf recognition element (MARE) and activates transcription of target genes. Although c-Maf is expressed in macrophages and directly regulates the expression of interleukin-10, detailed information regarding its function in the null mutant phenotype of tissue macrophages remain unknown. In this study, we demonstrated that c-Maf is specifically expressed in the F4/80 positive fetal liver and adult macrophages. The expression of F4/80, which is a tissue macrophage-specific seven trans-membrane receptor, was dramatically suppressed in the c-Maf-deficient macrophage, whereas the expression of Mac-1 was not affected, suggesting that c-Maf is not necessary for the lineage commitment of macrophages. Luciferase reporter and EMSA showed that c-Maf directly regulates the expression of F4/80 by interacting with the half-MARE site of the F4/80 promoter. These results suggest that c-Maf is required for the F4/80 expression in macrophages in vivo.
c-Maf是大型Maf转录因子之一，可与Maf识别元件（MARE）结合并激活靶基因的转录。尽管c-Maf在巨噬细胞中表达并直接调节白细胞介素-10的表达，但关于其在组织巨噬细胞无效突变表型中的功能的详细信息仍然未知。在本研究中，我们证明c-Maf在F4/80阳性的胎肝和成年巨噬细胞中特异性表达。F4/80是一种组织巨噬细胞特异性的七跨膜受体，其表达在c-Maf缺陷型巨噬细胞中显著受到抑制，而Mac-1的表达不受影响，这表明c-Maf对于巨噬细胞的谱系定向不是必需的。荧光素酶报告基因和电泳迁移率变动分析表明，c-Maf通过与F4/80启动子的半MARE位点相互作用直接调节F4/80的表达。这些结果表明，c-Maf是体内巨噬细胞中F4/80表达所必需的。
