title: Goblet Cell Hyperplasia Requires High Bicarbonate Transport To Support Mucin Release.
abstract: Goblet cell hyperplasia, a feature of asthma and other respiratory diseases, is driven by the Th-2 cytokines IL-4 and IL-13. In human bronchial epithelial cells, we find that IL-4 induces the expression of many genes coding for ion channels and transporters, including TMEM16A, SLC26A4, SLC12A2, and ATP12A. At the functional level, we find that IL-4 enhances calcium- and cAMP-activated chloride/bicarbonate secretion, resulting in high bicarbonate concentration and alkaline pH in the fluid covering the apical surface of epithelia. Importantly, mucin release, elicited by purinergic stimulation, requires the presence of bicarbonate in the basolateral solution and is defective in cells derived from cystic fibrosis patients. In conclusion, our results suggest that Th-2 cytokines induce a profound change in expression and function in multiple ion channels and transporters that results in enhanced bicarbonate transport ability. This change is required as an important mechanism to favor release and clearance of mucus.
authors: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors: Giulia
authors: G
authors: Gorrieri
authors: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors: Paolo
authors: P
authors: Scudieri
authors: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors: Emanuela
authors: E
authors: Caci
authors: Department of Thoracic Surgery, University of Padova, Italy.
authors: Marco
authors: M
authors: Schiavon
authors: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors: Valeria
authors: V
authors: Tomati
authors: Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
authors: Francesco
authors: F
authors: Sirci
authors: Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
authors: Francesco
authors: F
authors: Napolitano
authors: Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
authors: Diego
authors: D
authors: Carrella
authors: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors: Ambra
authors: A
authors: Gianotti
authors: Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
authors: Ilaria
authors: I
authors: Musante
authors: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy.
authors: Maria
authors: M
authors: Favia
authors: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy.
authors: Valeria
authors: V
authors: Casavola
authors: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy.
authors: Lorenzo
authors: L
authors: Guerra
authors: Department of Thoracic Surgery, University of Padova, Italy.
authors: Federico
authors: F
authors: Rea
authors: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.|DINOGMI, University of Genova, Italy.
authors: Roberto
authors: R
authors: Ravazzolo
authors: Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
authors: Diego
authors: D
authors: Di Bernardo
authors: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors: Luis J V
authors: LJ
authors: Galietta
mesh_terms: D001639:Bicarbonates / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D020397:Goblet Cells / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006965:Hyperplasia / Q000473:pathology*; D009077:Mucins / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D002712:Chlorides; D016207:Cytokines; D009077:Mucins