Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
Department of Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
Mol Med Rep. 2019 Feb;19(2):1272-1283. doi: 10.3892/mmr.2018.9747. Epub 2018 Dec 12.
Apolipoprotein M (ApoM) is a type of apolipoprotein. It is well known that high‑density lipoprotein (HDL) decreases inflammatory responses via the apoM‑sphingosine‑1‑phosphate (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 interleukin‑1β (IL‑1β), monocyte chemotactic protein‑1 (MCP‑1), S1P receptor‑1 (S1PR1) and 3β‑hydroxysterol Δ‑24‑reductase (DHCR24), as compared with in wild‑type 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 (rec‑apoM) or were induced to overexpress apoM (apoMTg); subsequently, cells were treated with tumor necrosis factor‑α (TNF‑α), in order to investigate the effects of ApoM on IL‑1β and MCP‑1. The results demonstrated that the mRNA expression levels of IL‑1β and MCP‑1 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 pre‑cultured with rec‑apoM or were engineered to overexpress apoM (apoMTg), they exhibited decreased expression levels of IL‑1β and MCP‑1 following TNF‑α treatment compared with in normal apoM‑expressing cells (apoMTgN). Furthermore, the mRNA expression levels of IL‑1β and MCP‑1 were significantly elevated following addition of the S1PR1 inhibitor W146, but not by the scavenger receptor class B type I inhibitor, block lipid transport‑1 (BLT‑1), in apoMTg cells prior to TNF‑α 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 BLT‑1 prior to TNF‑α 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.
载脂蛋白 M（ApoM）是一种载脂蛋白。众所周知，高密度脂蛋白（HDL）通过 ApoM-鞘氨醇-1-磷酸（S1P）途径降低炎症反应。本研究进一步探讨了 ApoM 在 HDL 抑制炎症中的重要性。使用载脂蛋白 M 基因缺失（apoM-/-）的小鼠来研究 ApoM 对白细胞介素-1β（IL-1β）、单核细胞趋化蛋白-1（MCP-1）、S1P 受体-1（S1PR1）和 3β-羟甾醇 Δ-24-还原酶（DHCR24）表达的影响，与野生型小鼠（apoM+/+）相比。此外，使用永生化人杂交内皮细胞系（EA.hy926）进行细胞培养实验。将细胞在重组人载脂蛋白 M（rec-apoM）存在下培养，或诱导过表达载脂蛋白 M（apoMTg）；随后，用肿瘤坏死因子-α（TNF-α）处理细胞，以研究 ApoM 对 IL-1β和 MCP-1 的影响。结果表明，脂多糖给药后，apoM-/-小鼠肝脏中 IL-1β和 MCP-1 的 mRNA 表达水平明显高于 apoM+/+小鼠。在细胞培养实验中，当细胞用 rec-apoM 预培养或被工程化以过表达 apoM（apoMTg）时，与正常表达 apoM 的细胞（apoMTgN）相比，用 TNF-α处理后 IL-1β和 MCP-1 的表达水平降低。此外，在用 S1PR1 抑制剂 W146 处理之前，apoMTg 细胞中 IL-1β和 MCP-1 的 mRNA 表达水平显著升高，但在用清道夫受体 B 类 I 抑制剂阻断脂质转运-1（BLT-1）处理之前，apoMTg 细胞中没有差异。相反，在相同条件下，apoMTgN 细胞中这些炎症生物标志物没有差异。在用 TNF-α处理之前，apoMTg 细胞中添加 BLT-1 可显著降低 DHCR24 的 mRNA 表达水平；然而，在 apoMTgN 细胞中，这种炎症生物标志物的表达没有差异。总之，ApoM 在体内和体外均表现出对炎症反应的抑制作用；这些作用可能是通过 S1PR1 和 DHCR24 途径诱导的。
