Regulatory peptides modulate ICAM-1 gene expression and NF-kappaB activity in bronchial epithelial cells.
Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule leading to adhesion between cells; NF-kappaB, 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-kappaB 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 kappaB (NF-kappaB) activation, we used immunocytochemistry, RT-PCR, and electrophoretic mobility-shift assay (EMSA) to determine the ICAM-1 expression and NF-kappaB activity in BECs. The effects of NF-kappaB 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-kappaB in O(3)-stressed BECs; CGRP and ET-1 promoted activation of NF-kappaB. These observations indicate that VIP and EGF abated the injury by means of down-regulatory effects on ICAM-1 transcription and NF-kappaB 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-kappaB.
Tan
Yu-Rong
YR
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, PR China. ttyyrr3668@sohu.com
Qin
Xiao-Qun
XQ
Guan
Cha-Xiang
CX
Zhang
Chang-Qing
CQ
Luo
Zi-Qiang
ZQ
Sun
Xiu-Hong
XH
D000818:Animals; D001980:Bronchi / Q000166:cytology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010455:Peptides / Q000502:physiology*; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D019332:Endothelin-1; D016328:NF-kappa B; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1; D014660:Vasoactive Intestinal Peptide