Soo-Jin Park, Kyoung-Pil Lee, Saeromi Kang, Jaewon Lee, Hae Young Chung, Dong-Soon Im (College of Pharmacy. Pusan National Univ.) Sato K, Okajima F (IMCR, Gunma Univ.）
About
Sphingosine 1-phosphate (S1P) has been implicated in anti-atherogenic properties of high-density lipoproteins. However, the roles and signaling of S1P in macrophages, the main contributor to atherosclerosis, have not been well studied. Furthermore, pro-inflammatory M1 and anti-inflammatory M2 macrophage phenotypes may influ-ence the development of atherosclerosis. Therefore, we investigated the effects of S1P on macrophage phenotypes, especially on M2 polarization and its signaling in relation to the anti-atherogenic properties of S1P. It was found that S1P induced anti-inflammatory M2 polarization via IL-4 secretion and its signaling, and induced IL-4Rα and IL-2Rγ. In addition, down-stream signalings, such as, stat-6 phosphorylation, SOCS1 induction, and SOCS3 suppression were also observed in macrophages in response to S1P. Furthermore, S1P-induced ERK activation, and the inhibitions of p38 MAPK and JNK were found to be key signals for IL-4 induction. Moreover, the anti-atherogenic effect of S1P in HDL was confirmed by the observation that oxidized LDL-induced lipid accumulation was attenuated in S1P-treated M2 macrophages. Furthermore, the atheroprotective effect of S1P was demonstrated by its anti-apoptotic effect on S1P-treated macrophages. The present study shows that S1P-induced M2 polarization of macrophages could be mediated via IL-4 signaling, and suggests that M2 polarization by S1P is responsible for the anti-atherogenic and atheroprotective properties of high-density lipoproteins in vivo.
Paper information
Sphingosine 1-phosphate induced anti-atherogenic and atheroprotective M2 macrophage polarization through IL-4.
Park SJ, Lee KP, Kang S, Lee J, Sato K, Chung HY, Okajima F, Im DS
Cell Signal 26: 2249-2258, 2014
Online URL
http://www.ncbi.nlm.nih.gov/pubmed/25035231
