Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Pro-Inflammatory Role of S1P3 in Macrophages

  • Received : 2018.11.05
  • Accepted : 2019.02.18
  • Published : 2019.07.01
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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 $S1P_1$ and $S1P_2$ on cell motility have been investigated. However, the function of $S1P_3$ has been poorly investigated. In this study, the roles of $S1P_3$ on inflammatory response were investigated in primary peritoneal macrophages. $S1P_3$ receptor was induced along with sphingosine kinase 1 by stimulation of lipopolysaccharide (LPS). LPS treatment induced inflammatory genes, such iNOS, COX-2, $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. TY52156, an antagonist of $S1P_3$ 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 $IL-1{\beta}$ induction was also confirmed by western blotting and ELISA. Caspase 1, which is responsible for $IL-1{\beta}$ production, was similarly induced by LPS and suppressed by TY52156. Therefore, we have shown $S1P_3$ induction in the inflammatory conditions and its pro-inflammatory roles. Targeting $S1P_3$ might be a strategy for regulating inflammatory diseases.

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References

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