Get access

Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression

Authors

  • Sarah K. Wise MD, MSCR,

    Corresponding author
    1. Department of Otolaryngology–Head and Neck Surgery, Emory University, Atlanta, GA
    • Correspondence to: Sarah K. Wise, MD, MSCR, Department of Otolaryngology–Head and Neck Surgery, Emory University, 550 Peachtree Street, MOT 9th Floor, Atlanta, GA 30308; e-mail: skmille@emory.edu

    Search for more papers by this author
  • Adrienne M. Laury MD,

    1. Department of Otolaryngology–Head and Neck Surgery, Emory University, Atlanta, GA
    Search for more papers by this author
  • Elizabeth H. Katz MD,

    1. Department of Otolaryngology–Head and Neck Surgery, Emory University, Atlanta, GA
    Search for more papers by this author
  • Kyle A. Den Beste BS,

    1. Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA
    Search for more papers by this author
  • Charles A. Parkos MD, PhD,

    1. Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA
    Search for more papers by this author
  • Asma Nusrat MD

    1. Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA
    Search for more papers by this author

  • Funding sources for the study: American Rhinologic Society New Investigator Award (to S.K.W.); NIH (NCRR KL2 RR025009 and UL1 RR025008 to PI David Stephens, MD, funding S.K.W.); NIH (NHLBI T35-HL007473 to PI Robinna G. Lorentz, MD, PhD, funding K.A.D.); NIH NIDDK (DK061379 and DK072564 to C.A.P.; DK059888 to A.N.).

  • Potential conflict of interest: None provided.

Abstract

Background

Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a “leaky” epithelial barrier phenotype. We hypothesize that T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 modulate epithelial junction proteins, thereby contributing to the leaky epithelial barrier.

Methods

Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis.

Results

IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n = 6) and 68.6% (n = 8) of baseline, respectively. Tight junction protein junctional adhesion molecule-A (JAM-A) expression decreased 42.2% with IL-4 exposure (n = 9) and 37.5% with IL-13 exposure (n = 9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n = 9) and 32.9% with IL-13 exposure (n = 9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or zonula occludens-1 (ZO-1) with IL-4 or IL-13 exposure.

Conclusion

Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity.

Ancillary