GLUT1 Promotes NLRP3 Inflammasome Activation of Airway Epithelium in Lipopolysaccharide-Induced Acute Lung Injury.
Am J Pathol
; 194(7): 1185-1196, 2024 07.
Article
em En
| MEDLINE
| ID: mdl-38548270
ABSTRACT
Acute lung injury (ALI) is a devastating clinical syndrome caused by different factors, with high morbidity and mortality. Lung injury and inflammation caused by lipopolysaccharide (LPS) can be modulated by NLRP3 inflammasome activation, yet its exact function within the airway epithelium is still unknown. Meanwhile, glucose transporter protein 1 (GLUT1) contributes to a number of inflammatory illnesses, including ALI. The present study aimed to assess GLUT1's function in NLRP3 inflammasome activation of airway epithelium in LPS-induced acute lung injury. BALB/c mice and BEAS-2B cells were exposed to LPS (5 mg/kg and 200 µg/mL, respectively), with or without GLUT1 antagonists (WZB117 or BAY876). LPS up-regulated pulmonary expression of NLRP3 and GLUT1 in mice, which could be blocked by WZB117 or BAY876. Pharmacological inhibition of GLUT1 in vivo significantly attenuated lung tissue damage, neutrophil accumulation, and proinflammatory factors release (TNF-α, IL-6, and IL-1ß) in LPS-exposed mice. Meanwhile, the activation markers of NLRP3 inflammasome (ASC, caspase-1, IL-1ß, and IL-18) induced by LPS were also suppressed. In cultured BEAS-2B cells, LPS induced an increase in GLUT1 expression and triggered activation of the NLRP3 inflammasome, both of which were inhibited by GLUT1 antagonists. These results illustrate that GLUT1 participates in LPS-induced ALI and promotes the activation of the NLRP3 inflammasome in airway epithelial cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
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Transportador de Glucose Tipo 1
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Lesão Pulmonar Aguda
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
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Camundongos Endogâmicos BALB C
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article