Recombinant TB10.4 of Mycobacterium bovis induces cytokine production in RAW264.7 macrophages through activation of the MAPK and NF-kappa B pathways via TLR2

文献类型： 外文期刊

第一作者： Liu, Shuqing

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

作者机构：

关键词： TB10.4;Mycobacterium bovis;Mitogen-activated protein kinase;NF-kappaB pathway;TLR2

期刊名称：MOLECULAR IMMUNOLOGY （ 影响因子：4.407； 五年影响因子：4.227 ）

ISSN： 0161-5890

年卷期： 2014 年 62 卷 1 期

页码：

收录情况： SCI

摘要： The TB10.4 antigen of Mycobacterium bovis/Mycobacterium tuberculosis induces a strong Th1 CD4+ T-cell response. Thus, it is currently under intensive study as a possible vaccine candidate. However, how TB10.4 activates innate immune cells is unclear. How TB10.4 interacts with toll-like receptors (TLRs) and signaling pathways responsible for active inflammation have also not been fully elucidated. Here, as stimulated RAW264.7 cells with recombinant TB10.4 (rTB10.4), derived from M. bovis, increased TNF-alpha, IL-6 and IL-12 p40 secretin in a dose-dependent manner. Blocking assays showed that TLR2-, but not TLR4-neutralizing antibody reduced expression of TNF-alpha, IL-6 and IL-12 p40 in RAW264.7 cells. rTB10.4 stimulation activated p38 kinase (p38) and extracellular-regulated kinase (ERK) was TLR2-dependent, whereas inhibition of p38 and ERK activity significantly reduced TNF-alpha, IL-6 and IL-12 p40 production. Furthermore, rTB10.4 stimulation of RAW264.7 cells resulted in TLR2-mediated activation of NF-kappa B and induced translocation of NF-kappa B p65 from the cytoplasm to the nucleus via I kappa B alpha degradation. rTB10.4-induced TNF-alpha, IL-6 and IL-12 p40 release was attenuated by the specific I kappa B phosphorylation inhibitor, BAY 11-7082. These findings indicate that the M. bovis-derived rTB10.4 induced production of TNF-alpha, IL-6 and IL-12 p40 involves p38, ERK and NF-kappa B via the TLR2 pathway. (C) 2014 Elsevier Ltd. All rights reserved.

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