The Induction of IL-33 in the Sinus Epithelium and Its Influence on T-Helper Cell Responses.

Abstract

BACKGROUND:

Chronic rhinosinusitis (CRS) is characterized by epithelial activation and chronic T-cell infiltration in sinonasal mucosa and nasal polyps. IL-33 is a new cytokine of the IL-1 cytokine family that has a pro-inflammatory and Th2 type cytokine induction property. The role of IL-33 in the pathomechanisms of CRS and its interaction with other T cell subsets remain to be fully understood.

METHODS:

The main trigger for IL-33 mRNA expression in primary human sinonasal epithelial cells was determined in multiple cytokine and T-cell stimulated cultures. The effects of IL-33 on naïve, Th0 and memory T-cells was studied by PCR, ELISA and flow cytometry. Biopsies from sinus tissue were analyzed by PCR and immunofluorescence for the presence of different cytokines and receptors with a special focus on IL-33.

RESULTS:

IL-33 was mainly induced by IFN-γ in primary sinonasal epithelial cells, and induced a typical CRSwNP Th2 favoring cytokine profile upon co-culture with T-helper cell subsets. IL-33 and its receptor ST2 were highly expressed in the inflamed epithelial tissue of CRS patients. While IL-33 was significantly up-regulated in the epithelium for CRSsNP, its receptor was higher expressed in sinus tissue from CRSwNP.

CONCLUSIONS:

The present study delineates the influence of IL-33 in upper airway epithelium and a potential role of IL-33 in chronic inflammation of CRSwNP by enhancing Th2 type cytokine production, which could both contribute to a further increase of an established Th2 profile in CRSwNP.

• Authors: Michael B Soyka, David Holzmann, Tomasz M Basinski, Marcin Wawrzyniak, Christina Bannert, Simone Bürgler, Tunc Akkoc, Angela Treis, Beate Rückert, Mübeccel Akdis, Cezmi A Akdis, Thomas Eiwegger
• Journal: PloS one (PLoS One) Vol. 10 Issue 5 Pg. e0123163 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25932636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Interleukin-33
• Interferon-gamma

Topics

• Cell Differentiation (drug effects)
• Chronic Disease
• Epithelial Cells (drug effects, metabolism, pathology)
• Humans
• Immunologic Memory (drug effects)
• Inflammation Mediators (metabolism)
• Interferon-gamma (pharmacology)
• Interleukin-33 (metabolism)
• Models, Biological
• Nasal Mucosa (drug effects, immunology, pathology)
• Paranasal Sinuses (pathology)
• Rhinitis (immunology, pathology)
• Sinusitis (immunology, pathology)
• T-Lymphocytes, Helper-Inducer (drug effects, immunology)
• Up-Regulation (drug effects)