Novel Function of Cyclooxygenase-2: Suppressing Mycobacteria by Promoting Autophagy via the Protein Kinase B/Mammalian Target of Rapamycin Pathway. (24th January 2018)

• Record Type: Journal Article
• Authors: Xiong, Wenjing; Wen, Qian; Du, Xialin; Wang, Jinli; He, Wenting; Wang, Ruining; Hu, Shengfeng; Zhou, Xinying; Yang, Jiahui; Gao, Yuchi; Ma, Li
• Is Part Of: Journal of infectious diseases. Volume 217:Number 8(2018)
• Page Start: 1267
• Page End: 1279
• Publication Date: 2018-01-24
• Subjects: Mycobacterium tuberculosis -- Bacillus Calmette-Guerin -- autophagy -- prostaglandins -- AKT/mTOR pathway -- cyclooxygenase-2; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy033
• Languages: English
• ISSNs: 0022-1899

Abstract

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 : Cyclooxygenase-2 plays an essential role in regulating autophagy-mediated mycobacterial elimination by inhibiting the activity of the protein kinase B/mammalian target of rapamycin pathway, a negative regulatory pathway of autophagy. These findings provide a novel perspective for developing therapeutic interventions for Mycobacterium tuberculosis infection.