Dihydroquercetin (DHQ) ameliorates LPS-induced acute lung injury by regulating macrophage M2 polarization through IRF4/miR-132-3p/FBXW7 axis.

BACKGROUND

Acute lung injury (ALI) is a common complication of sepsis. Dihydroquercetin (DHQ) has been found to attenuate lipopolysaccharide (LPS)-induced inflammation. However, the effect of DHQ on LPS-challenged ALI remains unclear.

METHODS

Pulmonary HE and TUNEL staining and lung wet/dry ratio were detected in LPS-treated Balb/c mice. IL-1β, IL-6 and TNF-α levels were determined utilizing ELISA assay. RAW264.7 cell apoptosis and macrophage markers (CD86, CD206) were tested using flow cytometry. TC-1 viability was analyzed by MTT assay. Western blot measured protein expression of macrophage markers. Interactions of miR-132-3p, IRF4 and FBXW7 were explored utilizing ChIP, RNA pull-down and dual luciferase reporter assays.

RESULTS

DHQ alleviated histopathological change, pulmonary edema and apoptosis in LPS-treated mice. DHQ affected LPS-induced M2 macrophage polarization and TC-1 cell injury-related indicators, such as decreased cell activity, decreased LDH levels, and increased apoptosis. LPS inhibited IRF4 and miR-132-3p expression, activated Notch pathway and increased FBXW7 level, which were overturned by DHQ. IRF4 transcriptionally activated miR-132-3p expression. FBXW7 was a downstream target of miR-132-3p.

CONCLUSION

DHQ alleviated LPS-induced lung injury through promoting macrophage M2 polarization via IRF4/miR-132-3p/FBXW7 axis, which provides a new therapeutic strategy for ALI.