Toll-Like Receptor Agonists Modulate Wound Regeneration in Airway Epithelial Cells.

Anna Lewandowska-Polak,Marzanna Jarzębska,Marcin Kurowski,Maciej Chałubiński,Małgorzata Brauncajs,Małgorzata Pawełczyk,Joanna Makowska,Marek Kowalski

doi:10.3390/ijms19082456

Anna Lewandowska-Polak, Marzanna Jarzębska + Show 6 more

Open Access

https://doi.org/10.3390/ijms19082456

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Abstract

Background: Impaired regeneration of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) in the stimulation of respiratory virus products in this process has not been established. Objective: This study was undertaken to test the hypothesis that the wound repair process in airway epithelium is modulated by microbial products via toll-like receptors. Methods: Injured and not-injured bronchial epithelial cells (ECs) (BEAS-2B line) were incubated with the TLR agonists poly(I:C), lipopolisacharide (LPS), allergen Der p1, and supernatants from virus-infected epithelial cells, either alone or in combination with TLR inhibitors. Regeneration and immune response in injured and not-injured cells were studied. Results: Addition of either poly(I:C) or LPS to ECs induced a marked inhibition of wound repair. Supernatants from RV1b-infected cells also decreased regeneration. Preincubation of injured and not-injured ECs with TLR inhibitors decreased LPS and poly(I:C)-induced repair inhibition. TGF-β and RANTES mRNA expression was higher in injured ECs and IFN-α, IFN-β, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-α and IFN-β mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. Conclusion: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors.

Highlights

The airway epithelium plays a protective role as a physical and functional barrier between the external milieu and underlying tissues
In the majority of cultures, full regeneration of damaged epithelium was observed 24 h post injury and in subsequent experiments we compared the effect of the toll-like receptors (TLRs) agonists Der p 1 and viral supernatants 24 h post injury
We have documented for the first time that toll-like receptors are involved in the modulation of airway epithelial cells regeneration

Summary

Introduction

The airway epithelium plays a protective role as a physical and functional barrier between the external milieu and underlying tissues This barrier is constantly injured and epithelial integrity is damaged. A wound repair process starts quickly after injury and includes activation and migration of cells from the epithelial basal layer to repopulate the damaged area followed by cell proliferation and differentiation as well as changes in gene expression This process provides the possibility for complete regeneration of a pseudostratified mucociliary epithelium [1,3]. Stimulation with poly(I:C) increased IFN-α and IFN-β mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. Conclusion: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors

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