Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells

Cell Tissue Res. 2009 Nov;338(2):283-93. doi: 10.1007/s00441-009-0855-1. Epub 2009 Sep 9.

Abstract

Epithelial-derived thymic stromal lymphopoietin (TSLP) triggers dendritic cell (DC)-mediated Th2-type inflammatory responses and is a master switch for allergic inflammatory diseases. In the present study, the expression and induction of TSLP and the effects of TSLP on the tight-junctional barrier of human nasal epithelial cells (HNECs) have been investigated in order to elucidate the role of TSLP in allergic rhinitis. We have found high expression of TSLP in the epithelium from patients with allergic rhinitis with recruitment and infiltration of DCs. In vitro, TSLP is significantly produced in HNECs after treatment with a toll-like receptor 2 (TLR2) ligand, Pam(3)Cys-Ser-(Lys)(4), and a mixture of interleukin-1beta and tumor necrosis factor-alpha. Treatment with TSLP rapidly enhances the barrier function of cultured HNECs, together with an increase of tight-junction proteins claudin-1, -4, -7, and occludin. The nasal-epithelial-derived TSLP thus not only activates DCs but also preserves the epithelial barrier via the upregulation of tight-junction proteins, thereby regulating antigen sensitization during the early stage of allergic rhinitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / drug effects
  • Cells, Cultured
  • Claudins / genetics*
  • Claudins / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Dendritic Cells / pathology*
  • Humans
  • Interleukin-1beta / pharmacology
  • Lipopeptides / pharmacology
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Nasal Mucosa / drug effects*
  • Nasal Mucosa / metabolism
  • Occludin
  • Rhinitis, Allergic, Perennial / pathology
  • Rhinitis, Allergic, Perennial / physiopathology
  • Thymic Stromal Lymphopoietin
  • Tight Junctions / drug effects*
  • Tight Junctions / metabolism
  • Toll-Like Receptor 2 / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation

Substances

  • Claudins
  • Cytokines
  • Interleukin-1beta
  • Lipopeptides
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Pam(3)CSK(4) peptide
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • Thymic Stromal Lymphopoietin