Quercetin induces itaconic acid-mediated M1/M2 alveolar macrophages polarization in respiratory syncytial virus infection.
Phytomedicine
; 130: 155761, 2024 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-38797031
ABSTRACT
BACKGROUND:
Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive.PURPOSE:
This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection.METHODS:
BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism.RESULTS:
Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes.CONCLUSION:
Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quercetina
/
Succinatos
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Macrófagos Alveolares
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Infecções por Vírus Respiratório Sincicial
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Proteína 3 que Contém Domínio de Pirina da Família NLR
/
Camundongos Endogâmicos BALB C
Limite:
Animals
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Alemanha