Specific Induction of TSLP by the Viral RNA Analogue Poly(I:C) in Primary Epithelial Cells Derived from Nasal Polyps.

Abstract

INTRODUCTION:

Chronic rhinosinusitis with nasal polyposis is an inflammatory disease that, although not directly linked to allergy, often displays a Th2-skewed inflammation characterized by elevated local IgE and IL-5 levels. The nasal cavity is constantly exposed to bacteria and viruses that may trigger epithelial inflammatory responses. To gain more insight into mechanisms by which such a biased inflammation might arise, we have investigated the epithelial expression of the Th2 skewing mediators (TSLP, IL-25, and IL-33) in relationship to disease and microbial triggers.

METHODS:

Epithelial cells were obtained from polyp tissues of nasal polyposis patients and from inferior turbinates of non-diseased controls. Cells were exposed to various TLR-specific triggers to study the effect on mRNA and protein expression level of TSLP, IL-25, and IL-33 and the potential regulatory mechanisms through the expression profile the transcription factors ATF-3, DUSP-1, EGR-1, and NFKB-1.

RESULTS:

The TLR3 agonist and viral analogue poly(I:C) induced TSLP mRNA 13.0 ± 3.1 fold (p < 0.05) and protein expression by 12.1 ± 2.3-fold (p < 0.05) higher in epithelium isolated from nasal polyposis patients than in epithelium form healthy controls. This enhanced induction of TSLP may be a consequence of a down-regulated expression of DUSP-1 in polyp epithelium.

CONCLUSION:

The TLR3 induced expression of TSLP introduces a mechanism by which the Th2-skewed tissue environment might arise in nasal polyps and invites a further evaluation of the potential contribution of current or past viral infections to polyposis pathogenesis.

• Authors: Korneliusz Golebski, Joost van Tongeren, Danielle van Egmond, Esther J de Groot, Wytske J Fokkens, Cornelis M van Drunen
• Journal: PloS one (PLoS One) Vol. 11 Issue 4 Pg. e0152808 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27050744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• RNA, Viral
• Poly I-C
• Thymic Stromal Lymphopoietin

Topics

• Cytokines (biosynthesis)
• Humans
• Nasal Polyps (metabolism, pathology)
• Poly I-C (metabolism)
• RNA, Viral (physiology)
• Thymic Stromal Lymphopoietin