HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/C957    most recent 00451.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Govindaraju, V. Articles by Martin, J. G. Search for Related Content PubMed PubMed Citation Articles by Govindaraju, V. Articles by Martin, J. G.

RECEPTORS AND SIGNAL TRANSDUCTION

Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration

¹Seymour Heisler Laboratory of the Montreal Chest Institute Research Center and Meakins-Christie Laboratories, McGill University, Montreal; and ²University of Montreal Hospital Center, Montreal, Quebec, Canada

Submitted 6 September 2005 ; accepted in final form 22 June 2006

In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with specific neutralizing antibodies, changes in [Ca²⁺]_i were abrogated. IL-8 also contracted the HASMC, decreasing the length of cells by 15%, and induced a 2.5-fold increase in migration. These results indicate that HASMC constitutively express functional CXCR1 and CXCR2 that mediate IL-8-triggered Ca²⁺ release, contraction, and migration. These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF.

chemokines; lung; signal transduction

This article has been cited by other articles:

				B. Moynihan, B. Tolloczko, M.-C. Michoud, M. Tamaoka, P. Ferraro, and J. G. Martin MAP kinases mediate interleukin-13 effects on calcium signaling in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L171 - L177. [Abstract] [Full Text] [PDF]

				M. L. D'Antoni, C. Torregiani, P. Ferraro, M.-C. Michoud, B. Mazer, J. G. Martin, and M. S. Ludwig Effects of decorin and biglycan on human airway smooth muscle cell proliferation and apoptosis Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L764 - L771. [Abstract] [Full Text] [PDF]

				J. Shannon, P. Ernst, Y. Yamauchi, R. Olivenstein, C. Lemiere, S. Foley, L. Cicora, M. Ludwig, Q. Hamid, and J. G. Martin Differences in Airway Cytokine Profile in Severe Asthma Compared to Moderate Asthma Chest, February 1, 2008; 133(2): 420 - 426. [Abstract] [Full Text] [PDF]

				R. B. Penn and J. L. Benovic Regulation of Heterotrimeric G Protein Signaling in Airway Smooth Muscle Proceedings of the ATS, January 1, 2008; 5(1): 47 - 57. [Abstract] [Full Text] [PDF]

				J. K. Bentley and M. B. Hershenson Airway Smooth Muscle Growth in Asthma: Proliferation, Hypertrophy, and Migration Proceedings of the ATS, January 1, 2008; 5(1): 89 - 96. [Abstract] [Full Text] [PDF]

				W. T. Gerthoffer Migration of Airway Smooth Muscle Cells Proceedings of the ATS, January 1, 2008; 5(1): 97 - 105. [Abstract] [Full Text] [PDF]

				K. Zhang, L. Shan, M. S. Rahman, H. Unruh, A. J. Halayko, and A. S. Gounni Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L375 - L382. [Abstract] [Full Text] [PDF]

				S. Dragon, M. S. Rahman, J. Yang, H. Unruh, A. J. Halayko, and A. S. Gounni IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L1023 - L1029. [Abstract] [Full Text] [PDF]