MicroRNA-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targeting PPAR{gamma}

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 targeting the 3'-UTR sequences of PPAR and inhibiting PPAR activation. Moreover, we found that PPAR activation not only inhibited CS/LPS-induced TLR2/4 expression and miR-27-3p-mediated TLR2/4 signaling cascades involving the NF-B, JNK/p38 and JAK/STAT pathways in AMs but also ameliorated CS/LPS-induced AM activation and pulmonary inflammation. Our study revealed that miR-27-3p ...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research