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Th2 Cytokines IL-4 and IL-13 Downregulate Paxillin Expression in Bronchial Airway Epithelial Cells

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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.

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Authors and Affiliations

  1. Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Veterans Affairs Medical Center, Indiana University, Bloomington, Indiana

    Gail Ramirez-Icaza, Kamal A. Mohammed, Najmunnisa Nasreen, Robert D. Van Horn, Joyce A. Hardwick, Kerry L. Sanders, Jun Tian, Carlos Ramirez-Icaza & Veena B. Antony

  2. Terre Haute Center for Medical Education, Indiana University School of Medicine, Indianapolis, Indiana

    Gail Ramirez-Icaza & Mary T. Johnson

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  1. Gail Ramirez-Icaza
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  2. Kamal A. Mohammed
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  3. Najmunnisa Nasreen
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Ramirez-Icaza, G., Mohammed, K.A., Nasreen, N. et al. Th2 Cytokines IL-4 and IL-13 Downregulate Paxillin Expression in Bronchial Airway Epithelial Cells. J Clin Immunol 24, 426–434 (2004). https://doi.org/10.1023/B:JOCI.0000029111.27168.c6

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  • DOI: https://doi.org/10.1023/B:JOCI.0000029111.27168.c6

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