In this study, the loss of body weight in S1P3 KO mice was significantly attenuated, suggesting that the inflammatory Teneligliptin response to bleomycin was reduced and that S1P3 deficiency was protective against the decline in physical health and feeding induced by bleomycin. During the acute phase of lung injury, H&E staining revealed less histological evidence of inflammation in the lungs of S1P3 KO mice than in those of WT mice, and analysis of BALF collected on the seventh day showed that S1P3 KO mice had a 56% reduction in total cell count compared with WT mice. These results are consistent with the observed changes in body weight. Sammani et al. showed that compared with control mice, S1P2 KO mice as well as mice with reduced S1P3 expression via silencing S1P3-containing nanocarriers were protected against LPS-induced barrier disruption. Singleton et al. also demonstrated that the activation of S1P3, which is expressed in both the alveolar epithelium and lung vascular endothelium, resulted in robust Rho/Rho kinase-mediated endothelial cell barrier disruption. These reports suggest a pro-inflammatory role for S1P3 in lung injury and are consistent with our results showing that S1P3 KO mice had less bleomycin-induced lung inflammation. In addition, these findings appear to be consistent with the results of our BALF analyses, which showed a reduction in total cell counts, but no differences in differential white blood cell profiles. On the other hand, some reports suggest an antiinflammatory role for S1P in lung injury. Intravenous administration of S1P significantly decreased pulmonary vascular leakage and inflammation in a murine model of LPS-mediated acute lung injury and canine models of acute lung injury induced by combined intrabronchial endotoxin administration and high tidal volume mechanical ventilation. Shea et al. showed that Phosalone short-term administration of S1P1 agonists prevented vascular leaks in models of acute lung injury; however, after prolonged exposure to these agents, they acted as functional antagonists of S1P1 and worsened pulmonary vascular leakage after injury.