Palmitate-Induced S1P Signaling Pathway Attenuates by Cchicoric Acid in Human Peripheral Blood Mononuclear Cells
Abstract Objective: Sphingosine 1-phosphate (S1P) signaling pathway is involved in the pathogenesis of type 2 diabetes (T2D). So, targeting S1P signaling pathway could be considered as potential therapeutic target for T2D. The aim of this study was to investigate the effects of palmitate and chicoric acid (CA) on S1P signaling pathway in peripheral blood mononuclear cells (PBMCs) from newly diagnosed patients with T2D and healthy subjects. Materials and Methods: 20 newly diagnosed patients with T2D and 20 healthy subjects, aged 40-60 years, were enrolled in the study. PBMCs were isolated and treated with palmitate and CA. Then, Sphingosine kinase 1 (SPHK1) and Sphingosine 1-phosphate receptor 1 (S1PR1) genes expression were evaluated by real-time PCR and S1PR1 protein levels were quantified using ELISA.Results: Palmitate significantly increased SPHK1 and S1PR1 genes expression and S1PR1 protein levels in PBMCs of both patients and healthy subjects. However, CA ameliorates palmitate-increased SPHK1 and S1PR1 genes expression and S1PR1 levels in these cells. Furthermore, a significant positive correlation between SPHK1 and S1PR1 genes expression with the S1PR1 protein levels was observed. Conclusions: These data indicate that CA could be considered as a novel S1P signaling pathway inhibitor through down regulation of SPHK1 and S1PR1.