Contribution of Thrombospondin‐1 and ‐2 to Lipopolysaccharide‐Induced Acute Respiratory Distress Syndrome
Qiang Li, Xiaoxiao Fu, Yuan Jiang, Shu Han
Abstract
Thrombospondin (TSP) proteins have been shown to impact T‐cell adhesion, migration, differentiation, and apoptosis. Thrombospondin‐1 (TSP‐1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide‐ (LPS‐) induced inflammation. In contrast, thrombospondin‐2 (TSP‐2) has been associated with activation of “anti‐inflammatory” T‐regulatory cells (Tregs). In this study, we investigated the effects of both TSP‐1 and TSP‐2 overexpression on macrophage polarization and activation in vitro and in vivo . We analyzed the effects of TSP‐1 and TSP‐2 on inflammation, vascular endothelial permeability, edema, ultrastructural morphology, and apoptosis in lung tissues of an ARDS mouse model and cultured macrophages. Our results demonstrated that TSP‐2 overexpression effectively attenuated LPS‐induced ARDS in vivo and promoted M2 macrophage phenotype polarization in vitro . Furthermore, TSP‐2 played a role in regulating pulmonary vascular barrier leakage by activating the PI3K/Akt pathway. Overall, our findings indicate that TSP‐2 can modulate inflammation and could therefore be a potential therapeutic target against LPS‐induced ARDS.