Th2 cytokines IL-4 and IL-13 downregulate paxillin expression in bronchial airway epithelial cells.
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.
Ramirez-Icaza
Gail
G
Division of Pulmonary Medicine, Veterans Affairs Medical Center, Indiana University, Bloomington, IN, USA.
Mohammed
Kamal A
KA
Nasreen
Najmunnisa
N
Van Horn
Robert D
RD
Hardwick
Joyce A
JA
Sanders
Kerry L
KL
Tian
Jun
J
Ramirez-Icaza
Carlos
C
Johnson
Mary T
MT
Antony
Veena B
VB
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
D003598:Cytoskeletal Proteins; D018793:Interleukin-13; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4