title: Interleukin-13 increases pendrin abundance to the cell surface in bronchial NCI-H292 cells via Rho/actin signaling.
abstract: Interleukin-13 (IL13) is a major player in the development of airway hyperresponsiveness in several respiratory disorders. Emerging data suggest that an increased expression of pendrin in airway epithelia is associated with elevated airway hyperreactivity in asthma. Here, we investigate the effect of IL13 on pendrin localization and function using bronchiolar NCI-H292 cells. The data obtained revealed that IL13 increases the cell surface expression of pendrin. This effect was paralleled by a significant increase in the intracellular pH, possibly via indirect stimulation of NHE. IL13 effect on pendrin localization and intracellular pH was reversed by theophylline, a bronchodilator compound used to treat asthma. IL13 upregulated RhoA activity, a crucial protein controlling actin dynamics, via G-alpha-13. Specifically, IL13 stabilized actin cytoskeleton and promoted co-localization and a direct molecular interaction between pendrin and F-actin in the plasma membrane region. These effects were reversed following exposure of cells to theophylline. Selective inhibition of Rho kinase, a downstream effector of Rho, reduced the IL13-dependent cell surface expression of pendrin. Together, these data indicate that IL13 increases pendrin abundance to the cell surface via Rho/actin signaling, an effect reversed by theophylline.
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125, Bari, Italy. marianna.ranieri@uniba.it.
authors.forename: Marianna
authors.initials: M
authors.lastname: Ranieri
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Di Mise
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dossena
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pellegrino
authors.affiliation: Department of Chemistry and Chemical Technologies, University of Calabria, Rende, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Furia
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Charity
authors.initials: C
authors.lastname: Nofziger
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Lucantonio
authors.initials: L
authors.lastname: Debellis
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125, Bari, Italy.|Istituto Nazionsale di Biostrutture e Biosistemi (I.N.B.B.), Rome, Italy.|Centre of Excellence Genomic and Proteomics GEBCA, University of Bari, Bari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Valenti
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125, Bari, Italy. grazia.tamma@uniba.it.|Istituto Nazionsale di Biostrutture e Biosistemi (I.N.B.B.), Rome, Italy. grazia.tamma@uniba.it.
authors.forename: Grazia
authors.initials: G
authors.lastname: Tamma
mesh_terms: D000199:Actins / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000076988:Sulfate Transporters / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D018793:Interleukin-13; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: Actin; Asthma; COPD; IL13; Pendrin; Rho signaling