School of Life Sciences and Biotechnology, Bio-X Research Center, Key Laboratory for Developmental Genetics and Neuropsychiatric Diseases (Ministry of Education), Shanghai Jiao Tong University, 800 Dongchuan Rd, 200240 Shanghai, China.
Int Immunopharmacol. 2010 Apr;10(4):461-6. doi: 10.1016/j.intimp.2009.12.019. Epub 2010 Jan 14.
Nicotine is a major component of cigarette smoking which may be involved in the progress of atherogenesis. In order to explain the mechanism of nicotine-induced endothelium dysfunction, we investigated the effects of nicotine on cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) expression in human umbilical vein endothelial cells (HUVECs). Nicotine treatment increased the expressions of COX-2 at mRNA and protein level in a dose-dependent manner, following prostaglandin E(2) (PGE(2)) release enhancement. Pyrrolidine dithiocarbamate (PDTC, NF-kappaB inhibitor) and alpha-Bungarotoxin (alpha-Btx, nicotinic acetylcholine receptor antagonist) attenuated the nicotine-induced COX-2 expression and PGE(2) production. Furthermore, nicotine-induced ICAM-1 expression was reduced by NS-398 (selective COX-2 inhibitor). Taken together, the present study demonstrated that nicotine-induced COX-2 expression through NF-kappaB activation which mediated by nicotinic acetylcholine receptor and the induction of COX-2 was related to ICAM-1 expression.
尼古丁是香烟的主要成分之一，可能与动脉粥样硬化的发生有关。为了阐明尼古丁诱导内皮功能障碍的机制，我们研究了尼古丁对人脐静脉内皮细胞（HUVEC）中环氧化酶-2（COX-2）和细胞间黏附分子-1（ICAM-1）表达的影响。结果显示，尼古丁呈剂量依赖性地增加 COX-2 的 mRNA 和蛋白表达，同时促进前列腺素 E2（PGE2）的释放。吡咯烷二硫代氨基甲酸盐（PDTC，NF-κB 抑制剂）和α-银环蛇毒素（α-Btx，烟碱型乙酰胆碱受体拮抗剂）可减弱尼古丁诱导的 COX-2 表达和 PGE2 的产生。此外，选择性 COX-2 抑制剂 NS-398 可降低尼古丁诱导的 ICAM-1 表达。综上所述，本研究表明，尼古丁通过烟碱型乙酰胆碱受体介导的 NF-κB 激活诱导 COX-2 表达，而 COX-2 的诱导与 ICAM-1 的表达有关。
