title: Upregulation of TMEM16A Protein in Bronchial Epithelial Cells by Bacterial Pyocyanin.
abstract: Induction of mucus hypersecretion in the airway epithelium by Th2 cytokines is associated with the expression of TMEM16A, a Ca2+-activated Cl- channel. We asked whether exposure of airway epithelial cells to bacterial components, a condition that mimics the highly infected environment occurring in cystic fibrosis (CF), also results in a similar response. In cultured human bronchial epithelial cells, treatment with pyocyanin or with a P. aeruginosa culture supernatant caused a significant increase in TMEM16A function. The Ca2+-dependent Cl- secretion, triggered by stimulation with UTP, was particularly enhanced by pyocyanin in cells from CF patients. Increased expression of TMEM16A protein and of MUC5AC mucin by bacterial components was demonstrated by immunofluorescence in CF and non-CF cells. We also investigated TMEM16A expression in human bronchi by immunocytochemistry. We found increased TMEM16A staining in the airways of CF patients. The strongest signal was observed in CF submucosal glands. Our results suggest that TMEM16A expression/function is upregulated in CF lung disease, possibly as a response towards the presence of bacteria in the airways.
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Caci
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Scudieri
authors.affiliation: Anatomic Pathology and Molecular Medicine, Department of Medicine and Sciences of Aging, "G. d'Annunzio" University, Chieti, Italy; Ce.S.I. Biotech, Aging Research Center, "G. d'Annunzio" University Foundation, Chieti, Italy.
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Morelli
authors.affiliation: Dept. of Experimental Medicine, DIMES, University of Genova, Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bruno
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: De Fino
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bragonzi
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Gianotti
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Sondo
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Loretta
authors.initials: L
authors.lastname: Ferrera
authors.affiliation: Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, University of Milan, Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palleschi
authors.affiliation: Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, University of Milan, Milano, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Santambrogio
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy; DINOGMI, University of Genova, Genova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Luis J V
authors.initials: LJ
authors.lastname: Galietta
mesh_terms: D000075369:Anoctamin-1; D001980:Bronchi / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011710:Pyocyanine / Q000494:pharmacology*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; D011710:Pyocyanine; D002118:Calcium