Qingwen Baidu Decoction attenuates acute lung injury via macrophage exosomal miR-146a suppression of alveolar epithelial cell pyroptosis.

BACKGROUND AND AIM: The anti-inflammatory and anti-pyroptosis effects of traditional Chinese medicine Qingwen Baidu Decoction (QBD), as well as the potential involvement of miR-146a from M2 alveolar macrophage exosomes in acute lung injury (ALI) remain uncharacterized. This study aims to explore the mechanism by which QBD attenuates lipopolysaccharide (LPS)-induced ALI and the involvement of alveolar macrophage exosomal miR-146a. EXPERIMENTAL PROCEDURE: Mouse models of LPS-induced ALI were treated with QBD and/or antago-miR-146a. Vascular permeability was assessed by wet/dry (W/D) ratio and total protein concentration of broncho-alveolar lavage fluid (BALF). BALF neutrophils were stained with Wright-Giemsa stain and counted. M2 macrophages were assessed by immunofluorescence. The exosomes and alveolar macrophages were isolated from BALF. Alveolar epithelial type Ⅱ cells (AEC-II) were isolated from lung tissues and incubated with the exosomes. TLR-4/NF-κB signaling and pyroptosis proteins were detected by western blotting and flow cytometry. RESULTS AND CONCLUSION: QBD treatment attenuated lung damage and enhanced M2 polarization. M2 secreted exosomal miR-146a was increased after QBD treatment. The exosomal miR-146a can be taken up by AEC-II to suppress AEC-II pyroptosis via inhibiting TLR4/NF-κB signaling pathway. Mid-to high-dose QBD increased miR-146a expression, suppressed TLR4/NF-κB signaling, and attenuated ALI in vivo. Inhibition of miR-146a abolished the protective effect of QBD against ALI. QBD increased miR-146a expression and secretion in M2 macrophage exosomes, decreased TLR4/NF-κB signaling in AEC II cells, and suppressed AEC-II pyroptosis, attenuating septic lung injury.