Resveratrol alleviates acute lung injury in mice by promoting Pink1/Parkin-related mitophagy and inhibiting NLRP3 inflammasome activation

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved..

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by rapid onset and widespread inflammation in the lungs, often leading to respiratory failure. These conditions can be triggered by various factors, resulting in a severe inflammatory response within the lungs. Resveratrol, a polyphenolic compound found in grapes and peanuts, is renowned for its potent antioxidative and anti-inflammatory properties. In this study, we investigated how resveratrol protects against lipopolysaccharide (LPS)-induced ALI in mice. We established mouse models of LPS-induced ALI and inflammation in bronchoalveolar lavage fluid (BALF) macrophages. Through histopathological examination, immunofluorescence, western blot, enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM), we assessed the impact of resveratrol on the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes and the process of mitophagy. Our findings indicate that resveratrol significantly mitigated the lung injury and inflammation caused by LPS. This was achieved by inhibiting the oligomerization of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and the activation of NLRP3 inflammasomes. Resveratrol also reduced the levels of IL-1β and IL-18 in serum and BALF, decreased caspase-1 expression, and diminished macrophage pyroptosis. Furthermore, it upregulated Pink1, Parkin, Beclin-1, Autophagy-Related 5 (Atg5), and Microtubule-Associated Proteins 1 A/1B Light Chain 3B (LC3B-II), thereby enhancing mitophagy. Conversely, mitophagy was inhibited by Pink1 siRNA. In conclusion, resveratrol ameliorated ALI in mice, potentially by inhibiting the activation of NLRP3 inflammasomes, activating the Pink1/Parkin pathway, and promoting mitophagy.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:1868

Enthalten in:

Biochimica et biophysica acta. General subjects - 1868(2024), 7 vom: 16. Apr., Seite 130612

Sprache:

Englisch

Beteiligte Personen:

Wu, Dongdong [VerfasserIn]
Zhang, Hui [VerfasserIn]
Li, Fang [VerfasserIn]
Liu, Shuai [VerfasserIn]
Wang, Yang [VerfasserIn]
Zhang, Zhao [VerfasserIn]
Wang, Jiannan [VerfasserIn]
Wu, Qiuge [VerfasserIn]

Links:

Volltext

Themen:

Acute lung injury
Alveolar macrophage
Journal Article
Mitophagy
NLRP3 inflammasome
Pink1/Parkin signaling pathway
Resveratrol

Anmerkungen:

Date Revised 26.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1016/j.bbagen.2024.130612

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM371159377