抑制聚二磷酸腺苷核糖聚合酶1减轻尼古丁诱导的支气管上皮细胞炎症反应  

Poly(ADP-ribose) polymerase 1 inhibition protects human bronchial endothelial cells against nicotine-induced inflammation response

作　　者：彭笑怒[1,2] 李文军[2] 田辉[1] 

机构地区：[1]山东大学齐鲁医院胸外科,济南250012 [2]烟台毓璜顶医院胸外科,山东烟台264000

出　　处：《山东大学学报（医学版）》2013年第2期37-43,共7页Journal of Shandong University:Health Sciences

摘　　要：目的通过检测尼古丁刺激的支气管上皮细胞中炎症因子的变化,探讨聚二磷酸腺苷核糖聚合酶1(PARP1)在Toll样受体4(TLR4)介导的炎症中的作用和机制。方法培养支气管上皮细胞。分别检测尼古丁刺激组及其阴性对照组、TLR4和PARP1抑制组及其阴性对照组中炎症因子相关基因、蛋白的表达量。结果与对照组比较,尼古丁刺激增加了TLR4和PARP1的蛋白表达。TLR4抑制减少了尼古丁诱导的诱导性一氧化氮合酶(iNOS)、细胞间黏附分子1(ICAM-1)和PARP1的上调。核因子κB的抑制减少了iNOS和ICAM-1的表达。抑制PARP1通过阻止核因子κB的核转位而减少了尼古丁诱导的炎症因子表达。结论尼古丁刺激通过TLR4/PARP1/NF-κB途径诱导ICAM-1和iNOS的表达。在尼古丁诱导、TLR4介导的炎症反应中,PARP-1或许是不可或缺的因素。在支气管上皮不典型增生中,PARP-1抑制或许是降低轻尼古丁诱导的炎症因子表达的有效手段。Objective To detect the changes of bronchial epithelial ceils inflammatory cytokine stimulated by nicotine and to investigate the function and mechanism of poly（ADP-ribose） polymerase 1 （PARP1） in the inflammatory response mediated by toll-like receptor 4 （TLR4）. Methods Bronchial epithelial cells were cultivated. The expressions of inflammatory cytokine-related gene and protein were detected in nicotine stimulation group, TLR4 and PARP1 inhibition group and their negative control groups. Results Compared with the controls, nicotine stimulation increased the protein expressions of TLR4 and PARP1. TLR4 inhibition reduced nicotine-induced up-regulations of iNOS, ICAM-1 and PARP1. NF-KB inhibition decreased ICAM-1 and iNOS expressions. PARP1 inhibition decreased protein expression of inflammatory cytokines induced by nicotine stimulation, probably through preventing NF-KB nuclear translocation. Conclusion Nicotine increases ICAM-1 and iNOS expressions via TLR4/PARP1/NF-KB pathway. PARPI might be a dispensable factor in TLR4-mediated inflammation after nicotine stimulation. PARP1 inhibition might shed a light on the decrease of nicotine-induced inflammatory cytokines expression during bronchial epithelium atypical heperplasia.

关 键 词：支气管上皮细胞 炎症因子 Toll样受体4 聚二磷酸腺苷核糖聚合酶1 核因子κB 尼古丁 

分 类 号：R562.2[医药卫生—呼吸系统]