GLUT1 Promotes NLRP3 In fl ammasome Activation of Airway Epithelium in Lipopolysaccharide-Induced Acute Lung Injury

Acute lung injury (ALI) is a devastating clinical syndrome caused by different factors, with high morbidity and mortality. Lung injury and in fl ammation caused by lipopolysaccharide (LPS) can be modulated by NLRP3 in fl ammasome activation, yet its exact function within the airway epithelium is still unknown. Meanwhile, glucose transporter protein 1 (GLUT1) contributes to a number of in fl am- matory illnesses, including ALI. The present study aimed to assess GLUT1 's function in NLRP3 in fl am- masome 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 mg/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 signi fi cantly attenuated lung tissue damage, neutrophil accumulation, and proin fl ammatory factors release (TNF- a, IL -6, and IL10) in LPS-exposed mice. Meanwhile, the activation markers of NLRP3 in fl ammasome (ASC, caspase-1, IL -10, 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 in fl ammasome, 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 in fl ammasome in airway epithelial cells. (Am J Pathol 2024, 194: