Role of uridine triggering M2 macrophage polarization to alleviate LPS-induced acute lung injury through the STAT6 signaling pathway

Acute respiratory distress syndrome (ARDS), the most severe presentation of acute lung injury (ALI), involves diffuse pulmonary inflammation and edema, with hypoxemic respiratory failure as the end result. Given the high mortality and limited therapeutic options, the development of novel interventions is urgently needed. Effective control of excessive pulmonary inflammation and modulation of alveolar macrophage polarization play critical roles in disease progression. In this study, we investigated the therapeutic potential of uridine in alleviating ALI. An in vivo model was established by intratracheal administration of lipopolysaccharide (LPS) in mice, and in vitro experiments were performed using LPS-stimulated MH-S cells. Our results demonstrated that uridine treatment significantly attenuated LPS-induced lung injury, as evidenced by reduced lung index (LI), wet-to-dry weight ratio (W/D), myeloperoxidase (MPO) activity, protein leakage and pro-inflammatory cytokine levels in lung tissues and bronchoalveolar lavage fluid (BALF), along with improved survival in mice. Mechanistically, uridine‑induced M2 polarization of alveolar macrophages was accompanied by STAT6 phosphorylation, suggesting a potential involvement of this pathway. Collectively, these findings suggest that uridine may serve as a promising adjunctive therapeutic agent for ALI, potentially improving disease outcomes through the induction of M2 macrophage polarization.