title: The epithelial anion transporter pendrin is induced by allergy and rhinovirus infection, regulates airway surface liquid, and increases airway reactivity and inflammation in an asthma model.
abstract: 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-gamma, 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.
authors.affiliation: Lung Biology Center, Department of Medicine, University of California, San Francisco, CA 94158, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakagami
authors.forename: Silvio
authors.initials: S
authors.lastname: Favoreto
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhen
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Louis T
authors.initials: LT
authors.lastname: Nguyenvu
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kuperman
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Dolganov
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Huang
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D027321:Anion Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008679:Metaplasia / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000378:metabolism; D010850:Picornaviridae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012229:Rhinovirus / Q000276:immunology*; D000076988:Sulfate Transporters; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D027321:Anion Transport Proteins; D016207:Cytokines; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D007073:Immunoglobulin E