Role of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice

Biochem Cell Biol. 2018 Jun;96(3):306-316. doi: 10.1139/bcb-2017-0126. Epub 2017 Oct 12.

Abstract

This study aimed to explore the effect of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500 μg/500 μL, intratracheal injection of 50 μL each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 μg/500 μL TSLP antibody, 50 μL each time) groups. ELISA was applied to measure the serum levels of immunoglobulin E (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon-γ (IFN-γ); flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis. RT-qPCR and Western blot assays were used to measure the levels of TSLP, OX40L, T-bet, GATA-3, NF-κB, p38, and ERK. Treatment with LY294002 and anti-TSLP resulted in increases in the numbers of total cells, eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells; lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-κB, p38, and ERK, whereas there were decreases in the levels of IFN-γ and CD4+CD25+Treg cells; CD4+Foxp3+Treg cells; and T-bet. The TSLP-DC-OX40L pathway may contribute to asthma pathogenesis and airway inflammation by modulating the levels of CD4+CD25+Treg cells and inflammatory cytokines.

Keywords: TSLP–DC–OX40L pathway; airway inflammation; asthma; asthme; inflammation de voies aériennes; modèle de souris; mouse model; pathogenesis; pathogenèse; sentier TSLP–CD–OX40L.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Asthma / drug therapy*
  • Asthma / immunology
  • Chromones / pharmacology*
  • Cytokines / blood
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Immunoglobulin E / blood
  • Immunoglobulins / drug effects*
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interferon-gamma / blood
  • Interleukin-13 / blood
  • Male
  • Mice
  • Morpholines / pharmacology*
  • OX40 Ligand / drug effects
  • OX40 Ligand / metabolism
  • Ovalbumin / pharmacology*
  • Receptors, Cytokine / drug effects*

Substances

  • Chromones
  • Cytokines
  • Immunoglobulins
  • Interleukin-13
  • Morpholines
  • OX40 Ligand
  • Receptors, Cytokine
  • Tslpr protein, mouse
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Immunoglobulin E
  • Interferon-gamma
  • Ovalbumin