Activation of alveolar macrophages (AMs) and the release of cytokines play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, little is known about the mechanisms of AM activation. miRNAs have recently emerged as key regulators of inflammation and as mediators of macrophage activation and polarization. We identified potential miRNAs related to AM activation using miRNA microarray analysis, which showed that miR-27-3p expression was up-regulated in AMs and the lung tissues of mice exposed to cigarette smoke (CS)/lipopolysaccharide (LPS), and found that miR-27-3p regulated proinflammatory cytokine production and AM polarization depending on TLR2/4 intracellular signaling in AMs. We also found that miR-27-3p controlled TLR2/4 signaling in AMs via targetting the 3′-UTR sequences of peroxisome proliferator-activated receptor γ (PPARγ) and inhibiting PPARγ activation. Moreover, we found that PPARγ activation not only inhibited CS/LPS-induced TLR2/4 expression and miR-27-3p-mediated TLR2/4 signaling cascades involving the nuclear factor-κB (NF-κB), c-Jun NH2-terminal kinase (JNK)/p38, and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways in AMs but also ameliorated CS/LPS-induced AM activation and pulmonary inflammation. Our study revealed that miR-27-3p mediated AM activation by the inhibition of PPARγ activation and sensitization of TLR signaling.
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Depiction of a macrophage. In issue 9 of Clinical science, Liu et al. discuss the role of miRNAs in alveolar macrophage activation; for details see pages 943–958.
Research Article|
May 14 2018
MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targetting PPARγ
Dan Wang;
Dan Wang
*
1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University (Chengdu), Chengdu 610041, P.R. China
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Sirong He;
Sirong He
*
2Department of Immunology, Chongqing Medical University, Chongqing 400016, P.R. China
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Bicui Liu;
Bicui Liu
1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University (Chengdu), Chengdu 610041, P.R. China
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Chuntao Liu
1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University (Chengdu), Chengdu 610041, P.R. China
Correspondence: Chuntao Liu ([email protected])
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Publisher: Portland Press Ltd
Received:
January 25 2018
Revision Received:
March 19 2018
Accepted:
March 23 2018
Accepted Manuscript online:
March 23 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (9): 943–958.
Article history
Received:
January 25 2018
Revision Received:
March 19 2018
Accepted:
March 23 2018
Accepted Manuscript online:
March 23 2018
Citation
Dan Wang, Sirong He, Bicui Liu, Chuntao Liu; MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targetting PPARγ. Clin Sci (Lond) 16 May 2018; 132 (9): 943–958. doi: https://doi.org/10.1042/CS20180083
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