| First Author | Wang M | Year | 2019 |
| Journal | Mol Med Rep | Volume | 19 |
| Issue | 2 | Pages | 1272-1283 |
| PubMed ID | 30569161 | Mgi Jnum | J:295134 |
| Mgi Id | MGI:6459676 | Doi | 10.3892/mmr.2018.9747 |
| Citation | Wang M, et al. (2019) Apolipoprotein M induces inhibition of inflammatory responses via the S1PR1 and DHCR24 pathways. Mol Med Rep 19(2):1272-1283 |
| abstractText | Apolipoprotein M (ApoM) is a type of apolipoprotein. It is well known that highdensity lipoprotein (HDL) decreases inflammatory responses via the apoMsphingosine1phosphate (S1P) pathway. The present study further investigated the importance of ApoM in the inhibitory effects of HDL on inflammation. Mice with an apoM gene deficiency (apoM/) were employed to investigate the effects of ApoM on the expression of interleukin1beta (IL1beta), monocyte chemotactic protein1 (MCP1), S1P receptor1 (S1PR1) and 3betahydroxysterol Delta24reductase (DHCR24), as compared with in wildtype mice (apoM+/+). Furthermore, cell culture experiments were performed using a permanent human hybrid endothelial cell line (EA.hy926). Cells were cultured in the presence of recombinant human apoM (recapoM) or were induced to overexpress apoM (apoMTg); subsequently, cells were treated with tumor necrosis factoralpha (TNFalpha), in order to investigate the effects of ApoM on IL1beta and MCP1. The results demonstrated that the mRNA expression levels of IL1beta and MCP1 were significantly higher in the liver following administration of lipopolysaccharide in apoM/ mice compared with in apoM+/+ mice. In cell culture experiments, when cells were precultured with recapoM or were engineered to overexpress apoM (apoMTg), they exhibited decreased expression levels of IL1beta and MCP1 following TNFalpha treatment compared with in normal apoMexpressing cells (apoMTgN). Furthermore, the mRNA expression levels of IL1beta and MCP1 were significantly elevated following addition of the S1PR1 inhibitor W146, but not by the scavenger receptor class B type I inhibitor, block lipid transport1 (BLT1), in apoMTg cells prior to TNFalpha treatment. Conversely, there were no differences in these inflammatory biomarkers under the same conditions in apoMTgN cells. The mRNA expression levels of DHCR24 were significantly reduced by the addition of BLT1 prior to TNFalpha treatment in apoMTg cells; however, there was no difference in the expression of this inflammatory biomarker in apoMTgN cells. In conclusion, ApoM displayed inhibitory effects against the inflammatory response in vivo and in vitro; these effects may be induced via the S1PR1 and DHCR24 pathways. |
