白细胞介素38过表达抑制氧化型低密度脂蛋白诱导内皮细胞炎症的分子机制研究  

IL-38 overexpression inhibits ox-LDL-induced endothelial inflammation

作　　者：杨嫣华[1,2] 李洺 何君宏 冯骏[1] 

机构地区：[1]西安交通大学第一附属医院血管外科,710061 [2]武警陕西省总队医院神经内科,西安710054 [3]西安市第九医院老年病二科,710054

出　　处：《免疫学杂志》2017年第5期415-421,共7页Immunological Journal

基　　金：陕西省自然科学基础研究计划(2012JM4005)

摘　　要：目的探究白细胞介素(IL)-38在动脉粥样硬化患者血清中的水平及其对氧化型低密度脂蛋白(ox-LDL)诱导的内皮细胞炎症的作用及分子机制。方法收集65例颅内外颈动脉粥样硬化患者和30例健康人的血液,ELISA检测血清中IL-38的表达。在人动脉内皮细胞(HAECs)中先转染pcDNA3.1-IL-38质粒过表达IL-38,然后用100μg/ml ox-LDL刺激。ELISA检测细胞上清液中IL-6、IL-8、IL-17、ICAM-1和MCP-1等炎性介质的表达;real-time PCR检测细胞中凝集素样氧化低密度脂蛋白受体-1(LOX-1)和CD36 mRNA水平的表达,Western blot检测细胞中LOX-1、CD36、磷酸化核内转录因子p65(p-NF-κB p65,p-p65)和IκB蛋白水平的表达。最后转染pcDNA3.1-IL-38质粒24 h后,用100μmol/L PDTC(NF-κB抑制剂)预处理HAECs2 h,再加入100μg/ml ox-LDL刺激,检测细胞中LOX-1、IL-6、IL-8、IL-17、ICAM-1和MCP-1的表达。结果与健康人相比,脑动脉粥样硬化患者血清中IL-38的表达明显增加(P<0.05),且与其动脉粥样硬化程度呈正相关性。IL-38能够降低ox-LDL诱导的IL-6、IL-8、IL-17、ICAM-1和MCP-1等炎性介质、LOX-1 mRNA和蛋白水平、p-p65的表达,增加IκB蛋白水平表达(P均<0.05),但是对CD36 mRNA和蛋白表达无影响。PDTC能够减弱IL-38对LOX-1、IL-6、IL-8、IL-17、ICAM-1和MCP-1表达的影响。结论 IL-38的表达水平与动脉粥样硬化程度呈正相关,它能够抑制ox-LDL诱导的内皮细胞炎症,这可能与其抑制NF-κB信号通路相关。This study aimed to investigate the expression of interleukin（IL）-38 in the serum of patients with atherosclerosis and further explore the role and molecular mechanism of IL-38 in ox-LDL induced endothelial inflammation. The blood samples of 65 intracranial and extracranial carotid atherosclerosis patients and 30 healthy control were collected and IL-38 level was determined by ELISA. Human aortic endothelial cells（HAECs） were transfected with pcDNA3.1-IL-38 plasmid to overexpress IL-38 and followed by stimulation with 100 μg/ml ox-LDL. The levels of inflammatory mediators（IL-6, IL-8, IL-17, ICAM-1, and MCP-1） in cell supernatants were measured by ELISA; the mRNA expression of lectin-like ox-LDL receptor 1（LOX-1） and CD36 were detected by real-time PCR; the protein levels of LOX-1, CD36, p-NF-κB p65（p-p65）, and IκB were examined by Western blotting. Additionally, the expression of LOX-1, IL-6,IL-8, IL-17, ICAM-1, and MCP-1 were assayed after HAECs were pretreated with 100 μmol/L PDTC（NF-κB inhibitor） and stimulated with 100 μg/ml ox-LDL. Data demonstrated that compared with healthy control, IL-38 level was significantly increased in theserum of cerebral atherosclerosis patients, and positively correlated with the atherosclerosis degree（P0.05）.Overexpression of IL-38 decreased ox-LDL-induced expression of inflammatory mediators, the m RNA and proteinexpression of LOX-1, and p-p65 level, but enhanced IκB expression（P0.05）, however, it did not alter the mRNA and protein expression of CD36. PDTC could attenuate the effects of IL-38 on the expression of LOX-1, IL-6, IL-8,IL-17, ICAM-1, and MCP-1. In conclusion, the expression level of IL-38 is involved in atherosclerosis degree.IL-38 could inhibit ox-LDL-induced endothelial inflammation, and the mechanism is related with the suppressionof NF-κB signaling pathway.

关 键 词：白细胞介素38 动脉粥样硬化 氧化型低密度脂蛋白 内皮细胞炎症 

分 类 号：R543.5[医药卫生—心血管疾病]