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- Title
Novel Function of Cyclooxygenase-2: Suppressing Mycobacteria by Promoting Autophagy via the Protein Kinase B/Mammalian Target of Rapamycin Pathway.
- Authors
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; Yang, Jiahui
- 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.
- Subjects
CYCLOOXYGENASE 2; MYCOBACTERIA; AUTOPHAGY; RAPAMYCIN; CANCER cells
- Publication
Journal of Infectious Diseases, 2018, Vol 217, Issue 8, p1267
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiy033