M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun
M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun
复制标题
M-CSF 与 NFκB 合作，通过上调 c-Jun 诱导巨噬细胞从 M1 向 M2 转化
DOI：
10.4161/cbt.26718
复制
发表时间：
2014-01-01
影响因子：
3.6
通讯作者：
Wang, Yue
中科院分区：
文献类型：
--
作者：
Yang, Yujiao;Qin, Junfang;Wang, Yue
越来越多的证据表明，与肿瘤相关的巨噬细胞（TAM）是巨噬细胞的极化M2亚型，它发挥促肿瘤作用并促进某些癌症的恶性肿瘤，但混凝土机制的定义不当。我们先前的研究表明，原始癌基因AP-1在巨噬细胞中调节IL-6的表达，并促进了M2巨噬细胞的形成。在这项研究中，我们研究了细胞外刺激M-CSF是否有助于此过程或核因子NFB在巨噬细胞的偏振M2亚型激活状态中具有协同作用。将RAW 264.7巨噬细胞和4T1小鼠乳腺癌细胞共培养以重建肿瘤微环境。与4T1或其上清液共同培养，AP-1家族成员C-Jun的表达在RAW 264.7巨噬细胞中的基因水平和蛋白质水平上都显着增加，但是C-的表达是FOS在基因水平和蛋白质水平上均未增加。与4T1共培养后，RAW 264.7的M-CSF消耗量要比RAW 264.7巨噬细胞更高。随着M-CSF的刺激，C-JUN的mRNA显着增加，但在添加抗M-CSF后明显下降。同时，NFB家族的成员P50也有类似的C-Jun趋势。 WB的结果表明，随着M-CSF的刺激，核中的P-JUN大大增加，但在添加中和抗体后会减少。共免疫沉淀和免疫印迹技术证实，C-JUN和P50 NFB共沉淀，C-JUN蛋白表达得到了RM-CSF效应的适当增强。总之，M-CSF通过用NFB的一定协同作用上调C-JUN来诱导巨噬细胞的转化。我们的研究可能提出针对癌症的新型治疗策略。
Increasing evidence suggests tumor-associated macrophages (TAMs) are polarized M2 subtype of macrophage that exerts pro-tumor effects and promote the malignancy of some cancers, but the concrete mechanism is not well defined. Our previous research exhibited that proto-oncogene AP-1 regulated IL-6 expression in macrophages and promoted the formation of M2 macrophages. In this study, we investigate whether extra-cellular stimulus M-CSF help this process or nuclear factor NFκB has a synergistic role in the activation state of polarized M2 subtype of macrophage. RAW 264.7 macrophage and 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. Being co-cultured with 4T1 or its supernatant, the expression of c-Jun, the member of AP-1 family, has a dramatically increase both on the level of gene and on the protein in RAW 264.7 macrophages, but the expression of c-Fos does not increase neither on the level of gene nor on the protein. After co-cultured with 4T1, RAW 264.7 has a higher consumption of M-CSF than RAW 264.7 macrophages alone. With the stimulation of M-CSF, the mRNA of c-Jun increased significantly, but decreased remarkably after adding the anti-M-CSF. And at the same time, p50, the member of NFκB family, has a similar tendency to c-Jun. WB results suggest that with the stimulation of M-CSF, p-Jun in nuclear increases heavily but decreases after the neutralizing antibody added. Coimmunoprecipitation and immunoblotting techniques confirmed that c-Jun and p50 NFκB coprecipitated, and c-Jun protein expression is properly enhanced with rM-CSF effect. In conclusion, M-CSF induces macrophage transformation by upregulating c-Jun with a certain synergy of NFκB. Our study may present a novel therapeutic strategy against cancer.