BACKGROUND: Migration of airway smooth muscle cells (ASMCs) might contribute to increased airway smooth muscle mass in asthma. T(H)17 cells and T(H)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 T(H)17-related cytokines. METHODS: The effect of exogenous T(H)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 T(H)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 T(H)17-associated cytokines promote human ASMC migration in vivo and suggest an important new mechanism for the promotion of airway remodeling in asthma.
BACKGROUND: Migration of airway smooth muscle cells (ASMCs) might contribute to increased airway smooth muscle mass in asthma. T(H)17 cells and T(H)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 T(H)17-related cytokines. METHODS: The effect of exogenous T(H)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 T(H)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 p38MAPK 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 T(H)17-associated cytokines promote human ASMC migration in vivo and suggest an important new mechanism for the promotion of airway remodeling in asthma.
Authors: Levi D Maston; David T Jones; Wieslawa Giermakowska; Tamara A Howard; Judy L Cannon; Wei Wang; Yongyi Wei; Weimin Xuan; Thomas C Resta; Laura V Gonzalez Bosc Journal: Am J Physiol Lung Cell Mol Physiol Date: 2017-02-17 Impact factor: 5.464
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: Roger R Beerli; Monika Bauer; Andrea Fritzer; Lindsey B Rosen; Regula B Buser; Markus Hanner; Melanie Maudrich; Mario Nebenfuehr; Jorge Alejandro Sepulveda Toepfer; Susanne Mangold; Anton Bauer; Steven M Holland; Sarah K Browne; Andreas Meinke Journal: MAbs Date: 2014 Impact factor: 5.857