Proceedings of the American Thoracic Society Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

The Proceedings of the American Thoracic Society 6:325-326 (2009)
© 2009 The American Thoracic Society
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hallstrand, T. S.
Right arrow Articles by Henderson, W. R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Hallstrand, T. S.
Right arrow Articles by Henderson, W. R., Jr.

Differential Epithelial and Mast Cell Gene Expression in Exercise-induced Bronchoconstriction

Teal S. Hallstrand1, Mark M. Wurfel1, Ying Lai1, Richard P. Beyer, Jr.3, Moira L. Aitken1 and William R. Henderson, Jr.2

Department of Medicine, 1 Divisions of Pulmonary and Critical Care and 2 Allergy and Infectious Diseases, and 3 Department of Environmental Health, University of Washington, Seattle, Washington

Correspondence and requests for reprints should be addressed to Teal S. Hallstrand, M.D., M.P.H., Assistant Professor of Medicine, University of Washington, Division of Pulmonary and Critical Care, Box 356522, 1959 NE Pacific Street, Seattle, WA 98195. E-mail: tealh{at}u.washington.edu

Background: Asthma is a phenotypically complex disease. Exercise-induced bronchoconstriction (EIB) occurs in 30 to 50% of individuals with asthma, representing increased indirect airway hyperresponsiveness (AHR). Objective: To gain a better understanding of the molecular basis of EIB, we determined differentially expressed genes in the lower airways of subjects with asthma susceptible to EIB as compared with subjects with asthma without EIB, but with direct AHR to methacholine. Methods: Subjects with asthma with AHR to methacholine (PC20 < 4 mg/ml) were divided into two groups: EIB+ subjects with asthma had a ≥ 20% decline in FEV1 and EIB– control subjects a ≤ 5% decline in FEV1 after exercise challenge (n = 7 per group). Genome-wide expression profiling of airway leukocytes and epithelial cells from induced sputum was conducted at baseline and on a separate day after exercise challenge. We identified genes with reproducible differential expression in an initial cohort and replicated these findings in a second cohort. Differentially expressed genes were confirmed by quantitative PCR in the entire population. Main Results: One gene, transglutaminase 2 (TGM2), was differentially expressed (Log2FC > 2, P < 0.001) in the EIB+ relative to EIB– subjects with asthma before exercise (baseline). After exercise challenge, 19 genes had increased expression (Log2FC > 2, P < 0.001) in the EIB+ relative to EIB– subjects with asthma, including trefoil factor 3 (TFF3), chloride channel, calcium activated, family member 1 (CLCA1), tryptase (TSPβ2, TSP{alpha}β1), cystatin SN (CST1), carboxypeptidase A3 (CPA3), kallikrein-related peptide 11 (KLK11), tretraspanins 1 and 8 (TSPAN 1 and 8), anterior gradient homolog 2 (AGR2), secretory leukoprotease inhibitor (SLPI), and mucin 5AC (MUC5AC). Conclusions: Processes related to epithelial repair and mast cell activation in the airways are more prominent in airways of individuals with asthma susceptible to EIB, and are transcriptionally activated by exercise challenge in susceptible individuals. These data provide new insights into the pathogenesis of EIB and the etiology of indirect AHR.

FOOTNOTES

Grant Funding: National Institutes of Health grants K23HL04231, R01HL72370, M01RR00037, and P30ES07033, and a Royalty Research Fund grant.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form July 14, 2008; accepted in final form November 4, 2008)





This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hallstrand, T. S.
Right arrow Articles by Henderson, W. R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Hallstrand, T. S.
Right arrow Articles by Henderson, W. R., Jr.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS