CAJ | 학술논문

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.
세포간점부분자-1 (ICAM-1)시개도세포여세포지간점부적중요생물분자; 핵인자-κB (NF-κB)시체내보편존재、능신속대자격산생반응적중요핵전록인자.월래월다적증거현시, ICAM-1표체여NF-κB격활시염증반응적중요보취.아문응용면역조화、RT-PCR、응효조체전영(EMSA)등다충실험방법, 관찰료폐내조절태대지기관상피세포ICAM-1표체급NF-κB활성적영향, 이급NF-κB억제제MG-132대ICAM-1표체적영향.실험결과발현, VIP、EGF가사취양응격BECs적ICAM-1표체강저; ET-1、CGRP가사미수응격BECs적ICAM-1표체증가.NF-κB억제제MG-132가조단O3、ET-1、CGRP인기적ICAM-1표체, 제시NF-κB재조공ICAM-1표체중기중요작용. EMSA결과현시, BECs중NF-κB재취양응격하반복격활,CGRP여ET-1가촉진NF-κB적격활; VIP여EGF가억제취양응격적BECs중NF-κB적격활.이상결과설명, VIP、EGF가통과하조ICAM-1전록급NF-κB격활감경염증반응, 이ET-1、CGRP가통과상조ICAM-1전록급NF-κB격활、가대염증반응.ICAM-1여NF-κB적지속표체화반복격활시염증지속가중발전적중요인소.
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.