单核细胞 C-C 趋化因子受体 5 的表达在体外间歇性低氧条件下和严重阻塞性睡眠呼吸暂停患者中增加。
Monocytic C-C chemokine receptor 5 expression increases in in vitro intermittent hypoxia condition and in severe obstructive sleep apnea patients.
机构信息
Sleep Center, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
School of Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
出版信息
Sleep Breath. 2019 Dec;23(4):1177-1186. doi: 10.1007/s11325-019-01797-4. Epub 2019 Feb 18.
PURPOSE
Obstructive sleep apnea (OSA) patients have higher risk of cardiovascular disease. C-C chemokine receptor 5 (CCR5), as an important receptor for monocyte recruitment and the initiation of atherosclerosis, was studied under intermittent hypoxia and in OSA patients.
METHODS
The expression and function of CCR5 regulated by intermittent hypoxia in monocytic THP-1 cells were investigated in an in vitro intermittent hypoxia culture system. The expression levels of protein and mRNA were analyzed by western blot and RT/real-time PCR analysis. Cell adhesion assay and transwell filter migration assay were carried out to investigate the adhesion and chemotaxis of monocytes. In addition, the mRNA expression of CCR5 in monocytes isolated from peripheral blood of 72 adults was analyzed.
RESULTS
Intermittent hypoxia upregulated the expression of CCR5 in THP-1 cells and enhanced the adhesion and chemotaxis of monocytes to vascular endothelial cells mediated by RANTES. The CCR5 expression induced by intermittent hypoxia was inhibited by inhibitor for p42/44 MAPK. Besides, the expression of CCR5 in monocytes increased along the AHI value especially in severe OSA patients that was statistically significant compared with mild and moderate OSA groups.
CONCLUSIONS
This study demonstrated the increased monocytic CCR5 gene expression in patients with severe OSA. Intermittent hypoxia, the characteristic of OSA, induced monocytic CCR5 gene expression and the enhanced RANTES-mediated chemotaxis and adhesion through p42/44 MAPK signal pathways.
目的
阻塞性睡眠呼吸暂停（OSA）患者心血管疾病风险较高。C-C 趋化因子受体 5（CCR5）作为单核细胞募集和动脉粥样硬化起始的重要受体，在间歇性低氧和 OSA 患者中进行了研究。
方法
在体外间歇性低氧培养系统中研究了单核细胞 THP-1 细胞中间歇性低氧调节的 CCR5 表达和功能。通过 Western blot 和 RT/实时 PCR 分析分析蛋白和 mRNA 的表达水平。通过细胞黏附试验和 Transwell 滤膜迁移试验研究单核细胞的黏附和趋化性。此外，分析了外周血中 72 例成年人单核细胞中 CCR5 的 mRNA 表达。
结果
间歇性低氧上调了 THP-1 细胞中 CCR5 的表达，并增强了 RANTES 介导的单核细胞对血管内皮细胞的黏附和趋化性。间歇性低氧诱导的 CCR5 表达被 p42/44 MAPK 抑制剂抑制。此外，CCR5 在单核细胞中的表达随着 AHI 值的增加而增加，尤其是在严重 OSA 患者中，与轻度和中度 OSA 组相比具有统计学意义。
结论
本研究表明，严重 OSA 患者单核细胞 CCR5 基因表达增加。间歇性低氧，即 OSA 的特征，通过 p42/44 MAPK 信号通路诱导单核细胞 CCR5 基因表达，并增强 RANTES 介导的趋化性和黏附性。
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