JNK通路对M2巨噬细胞极化及其肿瘤效应的影响

探究了JNK通路对M2巨噬细胞极化及M2介导的促肿瘤效应的影响。构建单核细胞THP1来源M2 巨噬细胞模型(THP1-M2),将细胞分为3组: 用PMA 诱导的未活化巨噬细胞组(M0),用PMA、IL-4处理及阴性干扰(DMSO)的M2型巨噬细胞组(M2),用特异性抑制剂阻断JNK通路的M2 型巨噬细胞组(M2-JNKI)。实时荧光定量PCR检测M2 表型marker基因的表达;免疫蛋白印迹法检测M2 表型marker蛋白水平;细胞划痕试验检测巨噬细胞迁移能力;流式细胞数检测786O及OSRC2凋亡。结果与THP1-M2组相比,阻断JNK通路的M2组M2表型marker表达明显下降,同时其细胞迁移能力也呈下降趋势。且阻断JNK通路后,M2巨噬细胞抑制肾癌细胞凋亡的能力减弱。结果表明,抑制JNK通路后,M2巨噬细胞极化状态受损,其促肿瘤效应可转变为抗肿瘤效应。

Effects of JNK Pathway on Polarization and Pro-tumor Function of M2 Macrophage

The present study investigates the effect of JNK pathway on the polarization of M2 status as well as pro-tumor function mediated by M2. THP1 derived M2 macrophage (THP1-M2) model was established. The cells were divided into 3 groups: the PMA pretreated unpolarized macrophage (M0), the PMA and IL-4 induced M2 macrophage with DMSO (negative control) treated (M2), the JNK inhibitor treated M2 macrophage (M2-JNK I). Furthermore, the M2 associated markers Arginase1 (Arg1),mannose receptor C-type 1 (Mrc1)were analyzed by Q-PCR, the protein level of Arg1 and Mrc1 were detected by Western blot, the migration ability of macrophages was tested by Wound Healing, the apoptosis of 786O and OSRC2 were analyzed by flow cytometry. Compared with the THP1-M2, THP1-M2-JNK I group showed decreased expression of Arg1 and Mrc1, and migration ability was impaired. What’s more, block of JNK pathway inhibited the pro-tumor function of M2 on 786O and OSCR2. Taken together, the results suggest that inhibition of JNK pathway regulates M2 polarization and its pro-tumor effects.