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.
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 humanASMC 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: Weimin Liu; Sucai Liu; Mukesh Verma; Iram Zafar; James T Good; Donald Rollins; Stephen Groshong; Magdalena M Gorska; Richard J Martin; Rafeul Alam Journal: J Allergy Clin Immunol Date: 2016-10-01 Impact factor: 10.793
Authors: Laila A Al-Alwan; Ying Chang; Andrea Mogas; Andrew J Halayko; Carolyn J Baglole; James G Martin; Simon Rousseau; David H Eidelman; Qutayba Hamid Journal: J Immunol Date: 2013-07-31 Impact factor: 5.422
Authors: Rabih Halwani; Roua Al-Kufaidy; Alejandro Vazquez-Tello; Mary Angeline Pureza; Ahmed S BaHammam; Hamdan Al-Jahdali; Sami A Alnassar; Qutayba Hamid; Saleh Al-Muhsen Journal: PLoS One Date: 2014-12-10 Impact factor: 3.240