Abstract
Sphingosine kinase 1 and its product, sphingosine 1-phosphate (S1P), as well as their receptors, have been implicated in inflammatory responses. The functions of receptors S1P1 and S1P2 on cell motility have been investigated. However, the function of S1P3 has been poorly investigated. In this study, the roles of S1P3 on inflammatory response were investigated in primary peritoneal macrophages. S1P3 receptor was induced along with sphingosine kinase 1 by stimulation of lipopolysaccharide (LPS). LPS treatment induced inflammatory genes, such iNOS, COX-2, IL-1β, IL-6 and TNF-α. TY52156, an antagonist of S1P3 suppressed the induction of inflammatory genes in a concentration dependent manner. Suppression of iNOS and COX-2 induction was further confirmed by western blotting and NO measurement. Suppression of IL-1β induction was also confirmed by western blotting and ELISA. Caspase 1, which is responsible for IL-1β production, was similarly induced by LPS and suppressed by TY52156. Therefore, we have shown S1P3 induction in the inflammatory conditions and its pro-inflammatory roles. Targeting S1P3 might be a strategy for regulating inflammatory diseases.