MiR-146a down-regulates inflammatory response by targeting TLR3 and TRAF6 in Coxsackievirus B infection

MiR-146a 通过靶向 TLR3 和 TRAF6 来下调柯萨奇病毒 B 感染中的炎症反应

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作者:Yanru Fei, Anita Chaulagain, Tianying Wang, Yang Chen, Jinchang Liu, Ming Yi, Ying Wang, Yike Huang, Lexun Lin, Sijia Chen, Weizhen Xu, Lei Tong, Xiaoyu Wu, Dechao Zhao, Fengmin Zhang, Wenran Zhao, Zhaohua Zhong

Abstract

Coxsackievirus B (CVB) is the major cause of human myocarditis and dilated cardiomyopathy. Toll-like receptor 3 (TLR3) is an intracellular sensor to detect pathogen's dsRNA. TLR3, along with TRAF6, triggers an inflammatory response through NF-κB signaling pathway. In the cells infected with CVB type 3 (CVB3), the abundance of miR-146a was significantly increased. The role of miR-146a in CVB infection is unclear. In this study, TLR3 and TRAF6 were identified as the targets of miR-146a. The elevated miR-146a inhibited NF-κB translocation and subsequently down-regulated proinflammatory cytokine expression in the CVB3-infected cells. Therefore, the NF-κB pathway can be doubly blocked by miR-146a through targeting of TLR3 and TRAF6. MiR-146a may be a negative regulator on inflammatory response and an intrinsic protective factor in CVB infection.

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