Document Detail


Autocrine-regulated airway smooth muscle cell migration is dependent on IL-17-induced growth-related oncogenes.
MedLine Citation:
PMID:  22698519     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Airway smooth muscle cell (ASMC) migration is one of the proposed mechanisms underlying the increased airway smooth muscle mass seen in airway remodeling of patients with severe asthma. IL-17-related cytokines are a new subgroup of inflammatory mediators that have been suggested to play a role in regulating smooth muscle function. We hypothesized that IL-17-induced chemokine production from smooth muscle cells can contribute to migration of additional smooth muscle cells in the airways of asthmatic patients. OBJECTIVE: We sought to investigate the effect of IL-17 on smooth muscle-derived chemokines and to examine the mechanisms involved in their production and contribution to the increase in airway smooth muscle migration. METHODS: The effect of IL-17-induced supernatants on human ASMC migration was investigated. IL-17-induced growth-related oncogene (GRO) production and mRNA expression was assessed by using ELISA and RT-PCR, respectively. The direct effect of GROs on ASMC migration and the involvement of the CXCR2 receptor were also examined. RESULTS: IL-17-induced supernatants promoted ASMC migration. After IL-17 stimulation, GROs were the most abundant chemokines produced from ASMCs, and blocking their effect by using neutralizing antibodies significantly inhibited ASMC migration. In addition, a combination of recombinant human GRO-α, GRO-β, and GRO-γ was able to promote significant migration of ASMCs that was mediated through the CXCR2 receptor. CONCLUSION: These findings suggest that IL-17-induced GROs can be an important mediator of ASMC migration and therefore might contribute to the pathogenesis of airway remodeling in asthmatic patients.
Authors:
Laila A Al-Alwan; Ying Chang; Carolyn J Baglole; Paul-André Risse; Andrew J Halayko; James G Martin; David H Eidelman; Qutayba Hamid
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-12
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  -     ISSN:  1097-6825     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Meakins-Christie Laboratories and the Respiratory Division, Department of Medicine, McGill University, Montreal, Quebec, Canada.
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