GLUT1 promotes NLRP3 inflammasome activation of airway epithelium in lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is a devastating clinical disease caused by different factors, with high morbidity and mortality. It has been shown that 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) has been shown to contribute to a number of inflammatory illnesses, including ALI. The present study was aimed to assess GLUT1's function in NLRP3 inflammasome activation of airway epithelium in LPS-induced acute lung injury. BALB/c mice (5 mg/kg) and BEAS-2B cells (200 μg/mL) were respectively exposed to LPS, with or without GLUT1 antagonists (WZB117 or BAY876). LPS upregulated 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-1β) in LPS-exposed mice. Meanwhile, the activation markers of NLRP3 inflammasome (ASC, caspase-1, IL-1β, and IL-18) induced by LPS were also suppressed. In cultured BEAS-2B cells, LPS induced an increase in GLUT1 expression and triggers activation of the NLRP3 inflammasome, both of which were inhibited by GLUT1 antagonists. These results illustrated that GLUT1 participates in LPS-induced ALI, and promotes the activation of the NLRP3 inflammasome in airway epithelial cells.