Mcl-1 signals pathway inhibitors in mouse peritoneal macrophage apoptosis infected with the Xinjiang strain of M. tuberculosis

Mcl-1信号通路抑制剂对结核分枝杆菌新疆株感染小鼠腹膜巨噬细胞凋亡的影响

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作者:Xiaofang Wang, Xinmin Wang, Le Zhang, Yuqing Zhang, Feiyu Wang, Yang Lu, Wanjiang Zhang, Jiangdong Wu

Abstract

A present, myeloid cell leukemia-1 (Mcl-1) was suggested as a potential new target for controlling latent TB infection. Therefore, we investigated the role of the Mcl-1 signalling pathway in mouse peritoneal macrophages infected with XJ-MTB, aiming at finding a new strategy for TB management in Xinjiang. We using TUNEL, Immunohistochemical analysis, ELISA, HE, RT-PCR and Western blot detected macrophages apoptosis, the damage of mice tissues and the expression of apoptosis genes and proteins. Results found that inhibition of the Mcl-1 signalling pathway not only reduced the survival of intracellular XJ-MTB, but also increased peritoneal macrophage apoptosis in latent XJ-MTB-infected mouse peritoneal macrophages and relieved the pathological damage of mouse organs infected with XJ-MTB, especially MAPK signalling pathway inhibitor PD98059 (P<0.05). Moreover, after inhibitor PD98059 treated mouse peritoneal macrophages infected with XJ-MTB, Bcl-2, Bax and Mcl-1 were reduced, while Cytochrome-c and Caspase-8 protein levels were significantly increased, and Cytochrome-c protein levels was significant higher than Caspase-8 (P<0.05). In conclusion, the MAPK signalling pathway inhibitor PD98059 down-regulated Mcl-1 expression and effectively increased macrophage apoptosis in mice infected with XJ-MTB. Furthermore, it also relief pathological organ damage and promote the elimination of inflammation. The intrinsic apoptotic pathway plays a predominant role in the regulatory role.

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