Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages  

作　　者：Qingshan Wang Hong Ni Lan Lan Xiaoli Wei Rong Xiang Yue Wang 

机构地区：[1]School of Medicine, Nankai University, Tianjin 300071, China [2]Tianjin Medical University, Tianjin Cancer Hospital Tianjin 300060, China

出　　处：《Cell Research》2010年第6期701-712,共12页细胞研究（英文版）

摘　　要：The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.

关 键 词：Fra-1 M2d IL-6 generation PHENOTYPE CO-CULTURE 

分 类 号：Q786[生物学—分子生物学] Q26