Regulatory peptides modulate adhesion of polymorphonuclear leukocytes to bronchial epithelial cells through regulation of interleukins, ICAM-1 and NF-kappaB/IkappaB.
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-kappaB 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-kappaB to the NF-kappaB binding site within the ICAM-1 promoter in ozone-stressed BECs, while CGRP and ET-1 promoted this binding activity. IkappaB degradation was consistent with NF-kappaB activation. These observations indicate that VIP and EGF inhibit inflammation, while ET-1 and CGRP enhance the inflammation reaction.
Xiangya School of Medicine, Central South University, Changsha 410078, China.
Jian-Song
JS
Zhang
Yu-Rong
YR
Tan
Yang
Y
Xiang
Zi-Qiang
ZQ
Luo
Xiao-Qun
XQ
Qin
D000818:Animals; D001483:Base Sequence; D001980:Bronchi / Q000166:cytology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D019332:Endothelin-1; D007375:Interleukin-1; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1; D014660:Vasoactive Intestinal Peptide; D004815:Epidermal Growth Factor; D051550:I-kappa B Kinase; D015740:Calcitonin Gene-Related Peptide