TH17 cytokines induce human airway smooth muscle cell migration.

Abstract

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.

• Authors: Ying Chang, Laila Al-Alwan, Paul-André Risse, Lucie Roussel, Simon Rousseau, Andrew J Halayko, James G Martin, Qutayba Hamid, David H Eidelman
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 127 Issue 4 Pg. 1046-53.e1-2 (Apr 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21345484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Cytokines

Topics

• Airway Remodeling (physiology)
• Asthma (immunology, metabolism, physiopathology)
• Cell Movement (physiology)
• Cell Separation
• Cytokines (immunology, metabolism)
• Flow Cytometry
• Humans
• Myocytes, Smooth Muscle (cytology, metabolism)
• Signal Transduction (physiology)
• Th17 Cells (immunology, metabolism)