Exploring the Protective Role and the Mechanism of Sphingosine 1 Phosphate in Endotoxic Cardiomyocytes.

FTY720 is a sphingosine 1 phosphate (S1P) receptor agonist approved for the treatment of multiple sclerosis, which is a chronic inflammatory autoimmune disorder. Sepsis is a complex syndrome associated with progressive endotoxemic developments, which finally leads to damage of multiple organs, including the heart. In critical patients, cardiovascular dysfunction due to sepsis is a major cause of death. Previous studies have shown an association between S1P and cardioprotection in the situation of ischemia reperfusion and myocardial infarction. Therefore, we will study the role of S1P towards endotoxic cardiomyocytes. Different doses of FTY720 were applied or not to endotoxic cardiomyocytes. The concentration of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 was measured by enzyme-linked immuno sorbent assay. Western blotting was used to analyze the downstream signaling pathways. We discovered that FTY720 reduced the levels of TNF-α and IL-6 through the NF-ΚB pathway, inhibited the expression of caspase-3, and activated both protein kinase B and extracellular signal-regulated kinase 1/2. Additionally, the activation of protein kinase B and extracellular signal-regulated kinase 1/2 could be inhibited by the S1P1 and S1P3 receptor antagonist vulcanized polyethylene23019. Therefore, we infer that S1P exerts a protective effect towards endotoxic cardiomyocytes by decreasing the levels of TNF-α and IL-6, regulating apoptotic and survival signaling pathway. The S1P1 and S1P3 receptors are involved in the prosurvival signal activation.

Pubmed ID: 30300318