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摘要: 目的:研究白细胞介素 (白介素) -37对人THP-1源巨噬细胞泡沫化的影响及机制。方法:体外培养THP-1, 用佛波酯 (PMA) 刺激24h使其分化为巨噬细胞后, 进行以下处理:①用IL-37和 (或) ox-LDL刺激THP-1源巨噬细胞24h;②用不同浓度的IL-37和ox-LDL同时刺激24h;③用ox-LDL刺激THP-1源巨噬细胞24h, 再加IL-37干预24h, 收集细胞。采用油红染色观察各组泡沫细胞所占细胞总数的比例, TC试剂盒测定细胞内TC的含量, 利用RT-PCR、Western blot实验方法从mRNA水平和蛋白水平测定泡沫细胞清道夫受体CD36和SRA和ABCA-1的表达。结果:与对照组比较, IL-37能够明显减少泡沫细胞的形成, 降低泡沫细胞TC的聚集[(303.10±8.90) ng/mg:(150.40±7.36) ng/mg, P<0.01], 显著抑制巨噬细胞清道夫受体CD36和SRA的表达, 并增强ABCA-1的表达, 且作用效果与溶度呈正相关。对ox-LDL诱导的泡沫细胞, 给予IL-37后仍能够显著上调ABCA1的表达, 显著下调SRA、CD36的表达。结论:白细胞介素-37可抑制THP-1源巨噬细胞的泡沫化, 其作用机制可能是通过IL-37抑制清道夫受体CD36和SRA、促进ABCA-1的表达实现的。Abstract: Objective:To investigate how IL-37 affects macrophages foam-cell formation, and thereby investigate the mechanism of IL-37 in the development of atherosclerosis.Method:THP-1 cells were differentiated into macrophages using 160 nMPMA for 24 h.And then with ox-LDL or IL-37 combine with ox-LDL, thereof in growth medium for 24 hours to transform macrophages into foam cells.THP-1 cells differentiated macrophages were stimulated with ox-LDL for 24 h, then with 10ng/ml IL-37 for another 24 hours.Oil red O staining and cellular lipid measurement were used to identify macrophage foam cell formation.Real-time PCR and Western blot were carried out to explore the mechanism of IL-37-mediated suppression on THP-1-macrophages derived foam cell formation.Result:Oil Red O staining identified foam cell formation was significantly reduced in cells treated with IL-37 and ox-LDL.The similar effect of IL-37 was obtained when extracted oil red O and measured by a spectrophotometer.Compared with ox-LDL alone, IL-37 and ox-LDL significantly reduced the lipids accumulation in macrophage foam cells in a concentration-dependent manner.Total cellular cholesterol was significantly reduced in IL-37 and ox-LDL cultures relative to ox-LDL alone[(150.4±7.36) ng/mg vs (303.1±8.9) ng/mg, P<0.01]. Moreover, real-time PCR and Western blot analysis showed that the expression of both CD36 and SRA of macrophage foam cells treated by ox-LDL together with IL-37was significantly down-regulated, while ABCA-1up-regulated significantly.Conclusion:IL-37may inhibit THP-1differentiated macrophage foam-cell formation, which is largely caused by a down-regulated expression of scavenger receptor SRA and CD36 and up-regulated expression of ABCA-1.
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Key words:
- interloukin-37 /
- scavenger receptor /
- THP-1 /
- macrophage foam cell
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