TH 17 cytokines induce human airway smooth muscle cell migration

• Published in: Journal of allergy and clinical immunology 2011, Vol.127 (4), p.1046-1053.e2
• Main Authors: Chang, Ying, PhD, Al-Alwan, Laila, PhD, Risse, Paul-André, PhD, Roussel, Lucie, PhD, Rousseau, Simon, PhD, Halayko, Andrew J., PhD, Martin, James G., MD, Hamid, Qutayba, MD, PhD, Eidelman, David H., MD, PhD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2010.12.1117

Background Migration of airway smooth muscle cells (ASMCs) might contribute to increased airway smooth muscle mass in asthma. TH 17 cells and TH 17-associated cytokines are involved in the pathogenesis of asthma and might also contribute to airway remodeling. Objective We sought to explore the possibility that migration of ASMCs might contribute to airway remodeling through the action of TH 17-related cytokines. Methods The effect of exogenous TH 17 cytokines on ex vivo human ASMC migration was investigated by using a chemotaxis assay. The involvement of signaling pathways, including p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 MAPK, nuclear factor κB, and phosphoinositide 3-kinase, was also examined. Results We demonstrated that IL-17A, IL-17F, and IL-22 promote migration in a dose-dependent manner. We further demonstrated that ASMCs express receptors for IL-17RA, IL-17RC, and IL-22R1. Using mAbs directed against these receptors, we confirmed that TH 17-associated cytokine–induced migration was dependent on selective receptor activation. Moreover, IL-17A and IL-17F exert their effects through signaling pathways that are distinct from those used by IL-22. The p38 MAPK inhibitor BIRB0796 inhibited the migration induced by IL-17A and IL-17F. PS1145, an inhibitor of nuclear factor κB, abolished the IL-22–induced migration. Conclusion These data raise the possibility that TH 17-associated cytokines promote human ASMC migration in vivo and suggest an important new mechanism for the promotion of airway remodeling in asthma.