Autocrine-regulated airway smooth muscle cell migration is dependent on IL-17–induced growth-related oncogenes

• Published in: Journal of allergy and clinical immunology 2012-10, Vol.130 (4), p.977-985.e6
• Main Authors: Al-Alwan, Laila A., PhD, Chang, Ying, PhD, Baglole, Carolyn J., PhD, Risse, Paul-André, PhD, Halayko, Andrew J., PhD, Martin, James G., MD, Eidelman, David H., MD, PhD, Hamid, Qutayba, MD, PhD
• Format: Article
• Language: English
• Subjects: airway remodeling; airway smooth muscle cells; Allergy and Immunology; Antibodies; Asthma; Autocrine Communication; Biological and medical sciences; Bronchi - cytology; Cell migration; Cell Movement - drug effects; Chemokine CXCL1 - genetics; Chemokine CXCL1 - physiology; Chemokines; Chronic obstructive pulmonary disease, asthma; CXCR2 protein; Cytokines; Enzyme-linked immunosorbent assay; Extracellular Signal-Regulated MAP Kinases - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Gro protein; growth-related oncogenes; Humans; IL-17; Immunopathology; Inflammation; Interleukin 17; Interleukin-17 - pharmacology; Medical sciences; migration; Muscular system; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - physiology; p38 Mitogen-Activated Protein Kinases - physiology; Pneumology; Polymerase chain reaction; Receptors, Interleukin-8B - physiology; Respiratory tract; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Smooth muscle; Studies
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.04.042

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.