Pro-Inflammatory Role of S1P₃ in Macrophages
10.4062/biomolther.2018.215
- Author:
Jae Yeong HEO
1
;
Dong Soon IM
Author Information
1. College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea. imds@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
S1P;
S1P₃;
Macrophage;
Inflammation;
Caspase 1;
GPCR
- MeSH:
Blotting, Western;
Caspase 1;
Cell Movement;
Enzyme-Linked Immunosorbent Assay;
Inflammation;
Interleukin-6;
Macrophages;
Phosphotransferases;
Sphingosine
- From:Biomolecules & Therapeutics
2019;27(4):373-380
- CountryRepublic of Korea
- Language:English
-
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.
