Recombinant TB9.8 of Mycobacterium bovis Triggers the Production of IL-12 p40 and IL-6 in RAW264.7 Macrophages via Activation of the p38, ERK, and NF-kappa B Signaling Pathways

文献类型： 外文期刊

第一作者： Jia, Hong

作者： Jia, Hong;Liu, Shuqing;Wu, Jing;Hou, Shaohua;Xin, Ting;Guo, Xiaoyu;Yuan, Weifeng;Zhang, Gaimei;Li, Ming;Zhu, Hongfei;Gao, Xintao;Qu, Hongfei;Zhu, Hongfei

作者机构：

关键词： TB9.8;Mycobacterium bovis;RAW264.7 cell;MAPK;NF-kappa B;signaling pathways

期刊名称：INFLAMMATION （ 影响因子：4.092； 五年影响因子：3.923 ）

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收录情况： SCI

摘要： The TB9.8 of Mycobacterium bovis can induce strong antigen-specific T-cell responses in proliferation assays and IFN-gamma assays. However, whether and how TB9.8 activates innate immune cells remain unclear. Therefore, recombinant protein TB9.8 (rTB9.8)-induced proinflammatory cytokine profile by RAW264.7 cells was investigated and the related signaling pathway was studied. Stimulation with rTB9.8 triggered RAW264.7 cells to produce IL-6 and IL-12 p40. In addition, rTB9.8 activated the mitogen-activated protein kinase (MAPK) cascade in RAW264.7 cells by inducing the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 kinase (p38) and also promoted nuclear translocation of phosphorylated p38 and ERK1/2. Furthermore, rTB9.8 activated nuclear factor kappa B (NF-kappa B) signaling pathway by inducing p65 translocation into the nucleus and the phosphorylation of I kappa B alpha in the cytosol. Blocking assays showed that specific inhibitors of ERK1/2, p38, and I kappa B alpha can significantly reduce the expression of IL-6 and IL-12 p40, which demonstrated that rTB9.8-mediated cytokine production is dependent on the activation of these kinases. Thus, this study demonstrates that rTB9.8 can activate RAW264.7 and trigger IL-6 and IL-12 p40 production via the ERK, p38, and NF-kappa B signaling pathways.

分类号： R3

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