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

Int J Mol Sci. 2018 Aug 20;19(8):2456. doi: 10.3390/ijms19082456.

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.

Keywords: LPS; TLRs; airway epithelium; poly(I:C); wound repair.

MeSH terms

  • Allergens / pharmacology
  • Antiviral Agents / pharmacology
  • Bronchi / drug effects
  • Bronchi / injuries
  • Bronchi / physiology
  • Bronchi / virology
  • Cell Line
  • Humans
  • Interferon Inducers / pharmacology
  • Lipopolysaccharides / pharmacology
  • Poly I-C / pharmacology
  • Regeneration / drug effects*
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / injuries
  • Respiratory Mucosa / physiology*
  • Respiratory Mucosa / virology
  • Toll-Like Receptors / agonists*
  • Toll-Like Receptors / antagonists & inhibitors
  • Wound Healing / drug effects*

Substances

  • Allergens
  • Antiviral Agents
  • Interferon Inducers
  • Lipopolysaccharides
  • Toll-Like Receptors
  • allergen Den n 1
  • Poly I-C