Dihydroquercetin (DHQ) ameliorates LPS-induced acute lung injury by regulating macrophage M2 polarization through IRF4/miR-132-3p/FBXW7 axis.
Acute lung injury
Dihydroquercetin
FBXW7
Macrophage M2 polarization
miR-132–3p
Journal
Pulmonary pharmacology & therapeutics
ISSN: 1522-9629
Titre abrégé: Pulm Pharmacol Ther
Pays: England
ID NLM: 9715279
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
07
06
2023
revised:
11
08
2023
accepted:
25
08
2023
pubmed:
31
8
2023
medline:
31
8
2023
entrez:
30
8
2023
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 37648017
pii: S1094-5539(23)00061-5
doi: 10.1016/j.pupt.2023.102249
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102249Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.