1. Novel Function of Cyclooxygenase-2: Suppressing Mycobacteria by Promoting Autophagy via the Protein Kinase B/Mammalian Target of Rapamycin Pathway.
- Author
-
Wenjing Xiong, Qian Wen, Xialin Du, Jinli Wang, Wenting He, Ruining Wang, Shengfeng Hu, Xinying Zhou, Jiahui Yang, Yuchi Gao, Li Ma, Xiong, Wenjing, Wen, Qian, Du, Xialin, Wang, Jinli, He, Wenting, Wang, Ruining, Hu, Shengfeng, Zhou, Xinying, and Yang, Jiahui
- Subjects
- *
CYCLOOXYGENASE 2 , *MYCOBACTERIA , *AUTOPHAGY , *RAPAMYCIN , *CANCER cells - Abstract
In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2) expression considerably increases to defend the body against mycobacteria by regulating adaptive immunity and restoring the mitochondrial inner membrane. Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important bactericidal mechanism. However, the association between M. tuberculosis-induced COX-2 and autophagy-mediated antimycobacterial response has not been explored. Here, COX-2 expression silencing reduced the autophagy and bactericidal activity against intracellular M. tuberculosis, while COX-2 overexpression reversed the above effects. In addition, enhancement of bactericidal activity was suppressed by inhibiting autophagy in COX-2-overexpressing cells, indicating that COX-2 accelerated mycobacterial elimination by promoting autophagy. Furthermore, the regulatory effects of COX-2 on autophagy were mediated by its catalytic products, which functioned through inhibiting the protein kinase B/mammalian target of rapamycin pathway. Thus, COX-2 contributes to host defense against mycobacterial infection by promoting autophagy, establishing the basis for development of novel therapeutic agents against tuberculosis by targeting COX-2. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF