Regulatory Peptides Modulate Adhesion of Polymorphonuclear Leukocytes to Bronchial Epithelial Cells through Regulation of Interleukins, ICAM-1 and NF-κB/IκB  

作　　者：Jian-Song ZHANG Yu-Rong TAN Yang XIANG Zi-Qiang LUO Xiao-Qun QIN 

机构地区：[1]Xiangya School of Medicine, Central South University, Changsha 410078, China

出　　处：《Acta Biochimica et Biophysica Sinica》2006年第2期119-128,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China （No. 30270586）

摘　　要：A complex network of regulatory neuropeptides controls airway inflammation reaction, in which airway epithelial cells adhering to and activating leukocytes is a critical step. To study the effect of intrapulmonary regulatory peptides on adhesion of polymorphonuclear leukocytes （PMNs） to bronchial epithelial cells （BECs） and its mechanism, several regulatory peptides including vasoactive intestinal peptide （VIP）, epidermal growth factor （EGF）, endothelin-1 （ET-1） and calcitonin gene-related peptide （CGRP）, were investigated. The results demonstrated that VIP and EGF showed inhibitory effects both on the secretion of IL-1, IL-8 and the adhesion of PMNs to BECs, whereas ET- 1 and CGRP had the opposite effect. Anti-intercellular adhesion molecule- 1 （ICAM-1） antibody could block the adhesion of PMNs to ozone-stressed BECs. Using immunocytochemistry and reverse transcription-polymerase chain reaction （RT-PCR）, it was shown that VIP and EGF down-regulated the expression of ICAM-1 in BECs, while ET-1 and CGRP up-regulated ICAM-1 expression. NF-r,B inhibitor MG132 blocked ICAM-1 expression induced by ET-1 and CGRP. Furthermore, in electric mobility shift assay （EMSA）, VIP and EGF restrained the binding activity of NF-κB to the NF-κB binding site within the ICAM-1 promoter in ozone-stressed BECs, while CGRP and ET-1 promoted this binding activity. IκB degradation was consistent with NF-κB activation. These observations indicate that VIP and EGF inhibit inflammation, while ET-1 and CGRP enhance the inflammation reaction.A complex network of regulatory neuropeptides controls airway inflammation reaction, in which airway epithelial cells adhering to and activating leukocytes is a critical step. To study the effect of intrapulmonary regulatory peptides on adhesion of polymorphonuclear leukocytes （PMNs） to bronchial epithelial cells （BECs） and its mechanism, several regulatory peptides including vasoactive intestinal peptide （VIP）, epidermal growth factor （EGF）, endothelin-1 （ET-1） and calcitonin gene-related peptide （CGRP）, were investigated. The results demonstrated that VIP and EGF showed inhibitory effects both on the secretion of IL-1, IL-8 and the adhesion of PMNs to BECs, whereas ET- 1 and CGRP had the opposite effect. Anti-intercellular adhesion molecule- 1 （ICAM-1） antibody could block the adhesion of PMNs to ozone-stressed BECs. Using immunocytochemistry and reverse transcription-polymerase chain reaction （RT-PCR）, it was shown that VIP and EGF down-regulated the expression of ICAM-1 in BECs, while ET-1 and CGRP up-regulated ICAM-1 expression. NF-r,B inhibitor MG132 blocked ICAM-1 expression induced by ET-1 and CGRP. Furthermore, in electric mobility shift assay （EMSA）, VIP and EGF restrained the binding activity of NF-κB to the NF-κB binding site within the ICAM-1 promoter in ozone-stressed BECs, while CGRP and ET-1 promoted this binding activity. IκB degradation was consistent with NF-κB activation. These observations indicate that VIP and EGF inhibit inflammation, while ET-1 and CGRP enhance the inflammation reaction.

关 键 词：polymorphonuclear leukocytes bronchial epithelial cells INTERLEUKINS intercellular adhesion molecule- 1 （ICAM- 1） NF-ΚB/IΚB 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]