Acta Physiologica Sinica, April 25, 2003, 55(2): 121-127

Received 2002-07-08 Accepted 2002-10-09

This project was supported by the National Natural Science Foundation of China (No. 30270586, 39800053).

Corresponding author. Tel: +86-731-2650401; E-mail: ttyyrr3668@sohu.com

Research Paper

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

TAN Yu-Rong, QIN Xiao-Qun*, GUAN Cha-Xiang, ZHANG Chang-Qing, LUO Zi-Qiang,

SUN Xiu-HongDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078

Abstract:

Intercellular 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 O3-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 O3, ET-1 and CGRP. The results obtained by using EMSA confirmed that VIP and EGF restrained the activation of NF-κB in O3-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.

Key words: intrapulmonary regulatory peptides; intercellular adhesion molecule-1 (ICAM-1); nuclear factor κB (NF-κB); bronchial epithelial cells

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

谭宇蓉, 秦晓群*, 管茶香, 张长青, 罗自强, 孙秀泓

中南大学湘雅医学院生理学教研室, 长沙 410078

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-132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-132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。 EMSA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NF-κB的持续表达和反复激活是炎症持续加重发展的重要因素。

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

中图分类号: Q471; R332.2