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Front. Pharmacol. | doi: 10.3389/fphar.2018.00142

Downregulation of TLR4 by miR-181a provides negative feedback regulation to Lipopolysaccharide-induced inflammation

 Kangfeng Jiang1,  Gan Zhao1, Tao Zhang1, Yaping Yang1, Shuai Guo1, Aftab Shaukat1,  Haichong Wu1 and  Ganzhen Deng1*
  • 1Huazhong Agricultural University, China

Acute lung injury (ALI) is a progressive clinical disease with a high mortality rate, and characterized by an excessive uncontrolled inflammatory response. MicroRNAs (miRNAs) play a critical role in various human inflammatory diseases, and have been recognized as important regulators of inflammation. However, the regulatory mechanisms mediated by miRNAs involved in LPS-induced inflammation in ALI remain hazy. In this study, we found that miR-181a expression in the lung tissues of ALI mice and LPS-stimulated RAW 264.7 macrophages is dramatically reduced. We also show that over-expression of miR-181a significantly decreased the production of inflammatory cytokines, such as such as IL-1β, IL-6 and TNF-α, whereas inhibition of miR-181a reversed this decrease. Moreover, miR-181a inhibits NF-κB activation and accumulation of reactive oxygen species (ROS) by targeting TLR4 expression. We further verify that miR-181a suppresses TLR4 expression by binding directly to the 3′-UTR of TLR4. Therefore, we provide the first evidence for the negative regulation of miR-181a in LPS-induced inflammation via the suppression of ROS generation and TLR4-NF-κB pathway.

Keywords: Acute Lung Injury, MiR-181a, LPS, NF-κB, ROS

Received: 26 Nov 2017; Accepted: 09 Feb 2018.

Edited by:

Marc Diederich, Seoul National University, South Korea

Reviewed by:

Amanda J. Gibson, Royal Veterinary College, United Kingdom
Parisa Kalantari, Tufts University School of Medicine, United States  

Copyright: © 2018 Jiang, Zhao, Zhang, Yang, Guo, Shaukat, Wu and Deng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Ganzhen Deng, Huazhong Agricultural University, Wuhan, China, ganzhendeng@sohu.com