Fingolimod attenuates renal ischemia/reperfusion-induced acute lung injury by inhibiting inflammation and apoptosis and modulating S1P metabolism

Abstract

Objective This study examined whether the immunomodulator fingolimod (FTY720) could alleviate renal ischemia/reperfusion (I/R)-induced lung injury and explored the potential mechanisms. Methods Renal I/R was established in a rat model, and FTY720 (0.5, 1, or 2 mg/kg) was injected intraperitoneally after 15 minutes of ischemia. Pro-inflammatory cytokine levels, oxidative stress, apoptosis, and the mRNA expression of the sphingosine-1-phosphate (S1P)-related signaling pathway genes sphingosine kinase-1 (SphK1) and sphingosine kinase-2 were analyzed in lung tissue. Results Increased pro-inflammatory cytokine levels; decreased total superoxide dismutase, catalase, and glutathione peroxidase levels; increased apoptosis; and increased S1P lyase and SphK1 expression were observed following renal I/R. FTY720 reversed renal I/R-induced changes and effectively attenuated lung injury. Conclusion FTY720 protected against acute lung injury in rats subjected to renal I/R by decreasing pulmonary inflammation and apoptosis, increasing oxidative stress, and modulating S1P metabolism.