Biomol Ther.  2019 Jul;27(4):373-380. 10.4062/biomolther.2018.215.

Pro-Inflammatory Role of S1P₃ in Macrophages

• Heo JY
• Im DS

• KMID: 2455092
• DOI: http://doi.org/10.4062/biomolther.2018.215

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 perito-neal 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.

Keyword

S1P; S1P₃; Macrophage; Inflammation; Caspase 1; GPCR

MeSH Terms

Blotting, Western
Caspase 1
Cell Movement
Enzyme-Linked Immunosorbent Assay
Inflammation
Interleukin-6
Macrophages*
Phosphotransferases
Sphingosine
Caspase 1
Interleukin-6
Phosphotransferases
Sphingosine