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* Lung Biology Center, Department of Medicine,
Division of Pulmonary/Critical Care Medicine, and
Graduate Program in Immunology, University of California, San Francisco, CA 94158;
Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and
¶ Division of Infectious Diseases and Geographic Medicine, Stanford Medical School, Stanford, CA 94305
Asthma exacerbations can be triggered by viral infections or allergens. The Th2 cytokines IL-13 and IL-4 are produced during allergic responses and cause increases in airway epithelial cell mucus and electrolyte and water secretion into the airway surface liquid (ASL). Since ASL dehydration can cause airway inflammation and obstruction, ion transporters could play a role in pathogenesis of asthma exacerbations. We previously reported that expression of the epithelial cell anion transporter pendrin is markedly increased in response to IL-13. Herein we show that pendrin plays a role in allergic airway disease and in regulation of ASL thickness. Pendrin-deficient mice had less allergen-induced airway hyperreactivity and inflammation than did control mice, although other aspects of the Th2 response were preserved. In cultures of IL-13-stimulated mouse tracheal epithelial cells, pendrin deficiency caused an increase in ASL thickness, suggesting that reductions in allergen-induced hyperreactivity and inflammation in pendrin-deficient mice result from improved ASL hydration. To determine whether pendrin might also play a role in virus-induced exacerbations of asthma, we measured pendrin mRNA expression in human subjects with naturally occurring common colds caused by rhinovirus and found a 4.9-fold increase in mean expression during colds. Studies of cultured human bronchial epithelial cells indicated that this increase could be explained by the combined effects of rhinovirus and IFN-
, a Th1 cytokine induced during virus infection. We conclude that pendrin regulates ASL thickness and may be an important contributor to asthma exacerbations induced by viral infections or allergens.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants HL085089 and AI50496, the University of California Sandler Asthma Basic Research Center, and the Ernest S. Bazley Grant to Northwestern University.
2 Address correspondence and reprint requests to Dr. David Erle, University of California Mail Code 2922, 1550 4th Street, San Francisco, CA 94158. E-mail address: david.erle{at}ucsf.edu
3 Abbreviations used in this paper: ASL, airway surface liquid; BAL, bronchoalveolar lavage; Cftr, cystic fibrosis transmembrane conductance regulator; CLCA1, chloride channel calcium activated 1; Ct, threshold cycle; ENaC, epithelial sodium channel; MTEC, mouse tracheal epithelial cells; NHBE, normal human bronchial epithelial; RV16, rhinovirus serotype 16; Scnn1a, sodium channel, nonvoltage-gated, type I, 
; Slc26a4, solute carrier family 26 member 4.
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  A C Madeo, A Manichaikul, S P Pryor, and A J Griffith Do mutations of the Pendred syndrome gene, SLC26A4, confer resistance to asthma and hypertension? J. Med. Genet., June 1, 2009; 46(6): 405 - 406. [Abstract] [Full Text] [PDF]
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