CCDC80对巨噬细胞源性泡沫细胞炎症因子表达的影响及机制  

The effect and mechanism of CCDC80 on the expression of inflammatory factors in macrophage-derived foam cells

作　　者：刘小飞 段永红 周敏 廖凌骁 廖泉 李靓[3] 龚朵 LIU Xiaofei;DUAN Yonghong;ZHOU Min;LIAO Lingxiao;LIAO Quan;LI Liang;GONG Duo(Department of Neurosurgery,the Second Affiliated Hospital of University of South China,Hengyang,Hunan 421001,China;Insititute of Pharmacology,University of South China,Hengyang,Hunan 421001,China;Institute of Cardiovascular Disease,University of South China&Key Laboratory for Arteriosclerology of Hunan Province,Hengyang,Hunan 421001,China)

机构地区：[1]南华大学附属第二医院神经外科,湖南省衡阳市421001 [2]南华大学药理研究所,湖南省衡阳市421001 [3]南华大学心血管疾病研究所动脉硬化学湖南省重点实验室,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2021年第2期116-122,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81800386);湖南省科卫联合项目(2020JJ8029);南华大学博士科研启动项目(190XQD120);湖南省教育厅项目(20C1604)。

摘　　要：目的探讨卷曲螺旋结合域蛋白80(CCDC80)对THP-1巨噬细胞源性泡沫细胞炎症因子表达的影响及相关分子机制。方法体外培养的THP-1细胞用佛波酯(160 nmol/L)处理,诱导分化为巨噬细胞,然后使用氧化型低密度脂蛋白(50 mg/L)处理使其荷脂形成泡沫细胞,并进行常规细胞体外培养。ELISA检测细胞炎性因子白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和单核细胞趋化蛋白1(MCP-1)的表达,实时荧光定量PCR和Western blot检测Toll样受体4(TLR4)、脂蛋白脂肪酶(LPL)和核因子κB(NF-κB)的表达。TLR4 siRNA和LPL siRNA分别处理泡沫细胞,采用荧光定量PCR和Western blot检测CCDC80对泡沫细胞TLR4、LPL、NF-κB和p-NF-κB表达的影响。结果 CCDC80显著增加THP-1巨噬细胞源性泡沫细胞炎症因子分泌以及p-NF-κB表达。TLR-4 siRNA处理细胞后,TLR4、LPL和p-NF-κB的表达显著降低。LPL siRNA处理泡沫细胞后,LPL和p-NF-κB的表达显著降低。结论 CCDC80通过TLR4/LPL途径促进NF-κB信号通路激活,从而增加细胞炎症因子IL-1β、IL-6、TNF-α和MCP-1分泌。Aim To investigate the effect of coiled-coil domain containing protein 80(CCDC80) on the expression of inflammatory factors in THP-1 macrophage-derived foam cells and related molecular mechanisms. Methods THP-1 cells were treated with phorbol ester(160 nmol/L) to induce the cells to differentiate into macrophages, and then treated with oxidized low density lipoprotein(50 mg/L) to form foam cell, performing conventional cell culture in vitro. The expression of interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and monocyte chemoattractant protein-1(MCP-1) was detected by ELISA, the expression of Toll like report 4(TLR4), lipoprotein lipase(LPL) and nuclear factor-κB(NF-κB) was detected by real-time PCR and Western blot. Foam cells were treated with TLR4 siRNA and LPL siRNA, and the effects of CCDC80 on the expression of TLR4, LPL, NF-κB and p-NF-κB in foam cells were detected by fluorescence quantitative PCR and Western blot. Results CCDC80 significantly increased THP-1 macrophage-derived foam cell inflammatory factor secretion and p-NF-κB expression. After TLR4 siRNA treated foam cells, the expression of TLR4, LPL and p-NF-κB reduced significantly. After LPL siRNA treated foam cells, the expression of LPL and p-NF-κB decreased significantly. Conclusion CCDC80 promotes the activation of NF-κB signaling pathway through the TLR4/LPL pathway, thereby increasing the secretion of IL-1β, IL-6, TNF-α and MCP-1.

关 键 词：卷曲螺旋结合域蛋白80 炎症因子 Toll样受体4 脂蛋白脂肪酶 核因子ΚB 

分 类 号：R363[医药卫生—病理学] R5[医药卫生—基础医学]