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.).
Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression
Article first published online: 7 FEB 2014
© 2014 ARS-AAOA, LLC
International Forum of Allergy & Rhinology
Volume 4, Issue 5, pages 361–370, May 2014
How to Cite
How to Cite this Article: Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression. Int Forum Allergy Rhinol. 2014;4:361–370., , , , , .
Potential conflict of interest: None provided.
- Issue published online: 25 APR 2014
- Article first published online: 7 FEB 2014
- Manuscript Accepted: 7 JAN 2014
- Manuscript Revised: 31 DEC 2013
- Manuscript Received: 27 AUG 2013
- American Rhinologic Society New Investigator Award
- NIH. Grant Numbers: NCRR KL2 RR025009, UL1 RR025008
- NIH. Grant Number: NHLBI T35-HL007473
- NIH NIDDK. Grant Numbers: DK061379, DK072564, DK059888
- epithelial cell;
- interleukin 4;
- interleukin 13;
- Th2 inflammation;
- allergic fungal sinusitis
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.
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.
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.
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.