Protumoral TSP50 Regulates Macrophage Activities and Polarization via Production of TNF-α and IL-1β, and Activation of the NF-κB Signaling Pathway.
Protumoral TSP50 Regulates Macrophage Activities and Polarization via Production of TNF-α and IL-1β, and Activation of the NF-κB Signaling Pathway.
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Protumoral TSP50 通过 TNF-α 和 IL-1β 的产生以及 NF-κB 信号通路的激活来调节巨噬细胞活动和极化
DOI：
10.1371/journal.pone.0145095
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Li YX
中科院分区：
文献类型：
--
作者：
Yang C;Zhang DM;Song ZB;Hou YQ;Bao YL;Sun LG;Yu CL;Li YX
睾丸特异性蛋白酶 50 (TSP50) 在多种癌症中异常过度表达，并促进细胞增殖和迁移。然而，TSP50是否能够影响肿瘤微环境，特别是微环境中免疫细胞的功能，目前仍不清楚。我们证明，暴露于 TSP50 过表达细胞的条件培养基，或与 TSP50 过表达细胞共培养，增强了巨噬细胞的细胞因子产生和吞噬活性，并诱导 M2b 极化。进一步研究表明，TSP50 过表达细胞中 TSP50 强烈诱导 TNF-α 和 IL-1β 的产生。 TSP50诱导的TNF-α和IL-1β是介导TSP50过表达细胞对巨噬细胞影响的主要因素。在 TSP50 过表达细胞的条件培养基处理后，巨噬细胞中的 NF-κB 通路可能被激活，并且其激活对于观察到的对巨噬细胞的影响是必要的。综上所述，我们的结果表明，细胞中表达的致癌 TSP50 可以激活周围的巨噬细胞并诱导 M2b 极化，部分是通过诱导 TNF-α/IL-1β 分泌和随后的 NF-κB 通路激活。这意味着癌基因 TSP50 调节肿瘤微环境以支持肿瘤发展的潜在机制。
Testes-specific protease 50 (TSP50) is abnormally overexpressed in many kinds of cancers and promotes cell proliferation and migration. However, whether TSP50 can influence the tumor microenvironment, especially the function of immune cells in the microenvironment, remains largely unknown. We demonstrated that exposure to the conditioned medium from TSP50-overexpressing cells, or co-culture with TSP50-overexpressing cells, enhanced the cytokine production and phagocytic activities of macrophages, and induced M2b polarization. Further investigation showed that production of TNF-α and IL-1β was strongly induced by TSP50 in TSP50-overexpressing cells. TSP50-induced TNF-α and IL-1β were main factors that mediated the effects of TSP50-overexpressing cells on macrophages. The NF-κB pathway could be activated in macrophages upon the treatment of conditioned medium of TSP50-overexpressing cells and its activation is necessary for the observed effects on macrophages. Taken together, our results suggested that oncogenic TSP50 expressed in cells could activate surrounding macrophages and induce M2b polarization, partly through inducing TNF-α/ IL-1β secretion and subsequent NF-κB pathway activation. This implies a potential mechanism by which oncogene TSP50 regulates tumor microenvironment to support tumor development.