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

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

  • Pulm Pharmacol Ther. 2023 Aug 28;102249. doi: 10.1016/j.pupt.2023.102249.
Chen Li 1,  Jianhua Liu 1,  Changhong Zhang 1,  Liang Cao 1,  Fang Zou 1,  Zhihua Zhang 2
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, Hebei Province, PR China.
  • 2 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, Hebei Province, PR China. Electronic address: [email protected].
PMID: 37648017 DOI: 10.1016/j.pupt.2023.102249
Abstract

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.

Keywords

Acute lung injury; Dihydroquercetin; FBXW7; Macrophage M2 polarization; miR-132–3p.

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