Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS.
Animals
Autophagosomes
/ drug effects
Berberine
/ pharmacology
Cell Line
Inflammasomes
/ metabolism
Macrophages
/ drug effects
Male
Membrane Proteins
/ metabolism
Mice, Inbred BALB C
Mitochondria
/ drug effects
Mitochondrial Proteins
/ metabolism
Mitophagy
/ drug effects
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Orthomyxoviridae
/ drug effects
Pneumonia
/ pathology
Reactive Oxygen Species
/ metabolism
Up-Regulation
/ drug effects
Berberine
NLRP3 inflammasome
influenza virus
mitophagy
Journal
Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
03
11
2019
revised:
05
03
2020
accepted:
09
03
2020
pubmed:
10
4
2020
medline:
2
12
2020
entrez:
10
4
2020
Statut:
ppublish
Résumé
Berberine (BBR) is an isoquinoline alkaloid extracted from several commonly used Chinese herbs. Our previous studies demonstrated BBR-mediated alleviation of lung injury due to inflammation and decrease in the mortality of mice with influenza viral pneumonia. The recent argument of autophagy against inflammatory responses has aroused wide concerns. This study focuses on the reactive oxygen species-Nod-like receptor protein 3 (ROS-NLRP3) pathway to investigate whether BBR inhibits NLRP3 inflammasome activation by inducing mitophagy. Our results demonstrate that BBR and mitochondrion-targeted superoxide dismutase mimetic (Mito-TEMPO; a specific mitochondrial ROS scavenger) significantly restricted NLRP3 inflammasome activation, increased mitochondrial membrane potential (MMP), and decreased mitochondrial ROS (mtROS) generation in J774A.1 macrophages infected with PR8 influenza virus. These observations suggest that the inhibitory effects of BBR on NLRP3 inflammasome activation were associated with the amelioration of mtROS generation. BBR treatment induced regular mitophagy, as evident from the increase in microtubule-associated protein 1 light chain 3 II, decrease in p62, colocalization of LC3 and mitochondria, and formation of autophagosomes. However, 3-methyladenine, an autophagy inhibitor, reversed the inhibitory effects of BBR on mitochondrial damage and NLRP3 inflammasome activation in influenza virus-infected macrophages, indicating the involvement of mitophagy in mediating the inhibitory effects of BBR on NLRP3 inflammasome activation. Furthermore, the knockdown of Bcl-2/adenovirus E18-19-kDa interacting protein 3 (BNIP3) expression attenuated the effects of BBR on mitophagy induction to some extent, suggesting that the BBR-induced mitophagy may be, at least in part, mediated in a BNIP3-dependent manner. Similar results were obtained in vivo using a mouse model of influenza viral pneumonia that was administered with BBR. Taken together, these findings suggest that restricting NLRP3 inflammasome activation by decreasing ROS generation through mitophagy induction may be crucial for the BBR-mediated alleviation of influenza virus-induced inflammatory lesions.
Identifiants
pubmed: 32272506
doi: 10.1002/JLB.3MA0320-358RR
doi:
Substances chimiques
BNip3 protein, mouse
0
Inflammasomes
0
Membrane Proteins
0
Mitochondrial Proteins
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Reactive Oxygen Species
0
Berberine
0I8Y3P32UF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
253-266Informations de copyright
©2020 Society for Leukocyte Biology.
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