肺内调节肽对支气管上皮细胞ICAM-1表达及NF-κB活性的调控(英文)  

Regulatory peptides modulate ICAM-1 gene expression and NF-κB activity in bronchial epithelial cells

作　　者：谭宇蓉[1] 秦晓群[1] 管茶香[1] 张长青[1] 罗自强[1] 孙秀泓[1] 

机构地区：[1]中南大学湘雅医学院生理学教研室,长沙410078

出　　处：《生理学报》2003年第2期121-127,共7页Acta Physiologica Sinica

基　　金：ThisprojectwassupportedbytheNationalNaturalScienceFoundationofChina (No 30 2 70 5 86,3980 0 0 5 3)

摘　　要：细胞间粘附分子 1(ICAM 1)是介导细胞与细胞之间粘附的重要生物分子 ;核因子 κB (NF κB)是体内普遍存在、能迅速对刺激产生反应的重要核转录因子。越来越多的证据显示 ,ICAM 1表达与NF κB激活是炎症反应的重要步骤。我们应用免疫组化、RT PCR、凝胶阻滞电泳 (EMSA)等多种实验方法 ,观察了肺内调节肽对支气管上皮细胞ICAM 1表达及NF κB活性的影响 ,以及NF κB抑制剂MG 13 2对ICAM 1表达的影响。实验结果发现 ,VIP、EGF可使臭氧应激BECs的ICAM 1表达降低 ;ET 1、CGRP可使未受应激BECs的ICAM 1表达增加。NF κB抑制剂MG 13 2可阻断O3、ET 1、CGRP引起的ICAM 1表达 ,提示NF κB在调控ICAM 1表达中起重要作用。EM SA结果显示 ,BECs中NF κB在臭氧应激下反复激活 ,CGRP与ET 1可促进NF κB的激活 ;VIP与EGF可抑制臭氧应激的BECs中NF κB的激活。以上结果说明 ,VIP、EGF可通过下调ICAM 1转录及NF κB激活减轻炎症反应 ,而ET 1、CGRP可通过上调ICAM 1转录及NF κB激活、加大炎症反应。ICAM 1与NFIntercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule leading to adhesion between cells; NF-κB, being universally distributed in the organism, is an important nuclear transcription factor leading to a rapid response to the stimuli. Line of evidence have shown that ICAM-1 transcription and NF-κB activation is an important step of inflammatory reaction. To testify that intrapulmonary regulatory peptides modulate inflammatory lesion of bronchial epithelial cells (BECs) through their effect on ICAM-1 expression and nuclear factor κB (NF-κB) activation, we used immunocytochemistry, RT-PCR, and electrophoretic mobility-shift assay (EMSA) to determine the ICAM-1 expression and NF-κB activity in BECs. The effects of NF-κB inhibitor MG-132 on ICAM-1 expression were also observed. The results showed that vasoactive intestinal peptide (VIP) and epidermal growth factor (EGF) decreased ICAM-1 expression in O 3-stressed BECs, while endothelin-1 (ET-1) and calcitonin gene-related peptides (CGRP) increased ICAM-1 expression in resting BECs. MG-132 blocked ICAM-1 expression induced by O 3, ET-1 and CGRP. The results obtained by using EMSA confirmed that VIP and EGF restrained the activation of NF-κB in O 3-stressed BECs; CGRP and ET-1 promoted activation of NF-κB. These observations indicate that VIP and EGF abated the injury by means of down-regulatory effects on ICAM-1 transcription and NF-κB activation, while ET-1 and CGRP enhanced the inflammation reaction by an up-regulatory effect. It is suggested that a developing and intensive airway inflammation correlates closely with a persistent expression of ICAM-1 and repeated activation of NF-κB.

关 键 词：肺内调节肽 细胞间粘附分子-1 核因子-ΚB 支气管上皮细胞 

分 类 号：R332[医药卫生—人体生理学]