title: Th2 cytokines IL-4 and IL-13 downregulate paxillin expression in bronchial airway epithelial cells.
abstract: Asthma is characterized by infiltration and shedding of the bronchial epithelium. The Th2 cytokines IL-4 and IL-13 are involved in the cellular recruitment and infiltration seen in asthma. The effects of IL-4 and IL-13 on cell-matrix interactions and epithelial shedding are unknown. We hypothesize that bronchial airway epithelial cells (BAEC) express paxillin, a structural focal adhesion protein, and downregulation of paxillin by Th2 cytokines lead to BAEC hyperpermeability. We showed by confocal microscopy the presence of paxillin in BAEC. We demonstrated by Western blot analysis that IL-4 and IL-13 stimulation results in downregulation of paxillin production. IL-4 and IL-13 stimulation decreased epithelial cell-matrix attachment as measured by electrical cell-substrate impedance sensing system (ECIS). Our results suggest that Th2 cytokines IL-4 and IL-13 downregulate paxillin production by BAEC, thereby disrupting the cell-matrix interactions. This may help explain the epithelial shedding and epithelial membrane hyperpermeability that occurs in asthma.
authors.affiliation: Division of Pulmonary Medicine, Veterans Affairs Medical Center, Indiana University, Bloomington, IN, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Ramirez-Icaza
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Mohammed
authors.forename: Najmunnisa
authors.initials: N
authors.lastname: Nasreen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Van Horn
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Hardwick
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Sanders
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.forename: Carlos
authors.initials: C
authors.lastname: Ramirez-Icaza
authors.forename: Mary T
authors.initials: MT
authors.lastname: Johnson
authors.forename: Veena B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D001980:Bronchi / Q000166:cytology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D051419:Paxillin; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics*; D018418:Th2 Cells; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D003598:Cytoskeletal Proteins; D018793:Interleukin-13; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4