Crucial role of OX40/OX40L signaling in a murine model of asthma.

Abstract

The aim of the present study was to explore the roles of OX40/OX40 ligand (OX40L) signaling and OX40+ T cells in ovalbumin (OVA)‑induced mouse asthma model. Asthma was induced by OVA exposure and subsequent co‑treatment with OX40L protein, neutralizing anti‑OX40L blocking antibody, OX40+ T cells or PBS. The protein expression levels of interleukin (IL)‑4, IL‑6, IL‑13, IL‑17, tumor necrosis factor (TNF)‑α and interferon (IFN)‑γ in bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific ELISA. Eosinophil accumulation as well as proliferation and apoptosis of T cells in BALF were detected by Cell Counting kit‑8 and flow cytometric assays. Expression of the apoptosis‑related protein cleaved caspase‑3 was examined in OX40+ T cells using western blot assay. Flow cytometric analysis revealed that OVA‑treated mice that were co‑treated with OX40L or OX40+ T cells exhibited higher eosinophil infiltration compared with control mice treated only with OVA, whereas neutralizing anti‑OX40L blocking antibody inhibited eosinophil infiltration. ELISA assays demonstrated that the expression of IL‑4, IL‑6, IL‑13, IL‑17, TNF‑α and IFN‑γ in BALF in OX40L‑treated and OX40+ T cell‑treated mice was increased compared with expression levels in control mice. Treatment with OX40L protein effectively reduced apoptosis of T cells and the expression of cleaved caspase‑3 in T cells. OX40L‑treated and OX40+ T cell‑treated mice exhibited increased asthma through OX40/OX40L signaling, which probably promoted inflammatory factor expression, eosinophil infiltration and T cell proliferation.

• Authors: Wei Lei, Daxiong Zeng, Gaoqin Liu, Yehan Zhu, Jiajia Wang, Hongya Wu, Junhong Jiang, Jianan Huang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 17 Issue 3 Pg. 4213-4220 (03 2018) ISSN: 1791-3004 [Electronic] Greece
• PMID: 29344664 (Publication Type: Journal Article)

Chemical References

• Antibodies, Neutralizing
• Antigens, Differentiation
• Interleukin-13
• Interleukin-17
• Interleukin-6
• Membrane Glycoproteins
• OX40 Ligand
• OX40Ig
• Tnfsf4 protein, mouse
• Tumor Necrosis Factor Inhibitors
• Tumor Necrosis Factor-alpha
• Tumor Necrosis Factors
• interleukin-6, mouse
• Interleukin-4
• Interferon-gamma
• Ovalbumin
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Antibodies, Neutralizing (pharmacology)
• Antigens, Differentiation (genetics, metabolism)
• Apoptosis (drug effects)
• Asthma (chemically induced, genetics, immunology, therapy)
• Bronchoalveolar Lavage Fluid (chemistry, cytology, immunology)
• CD4-Positive T-Lymphocytes (drug effects, immunology, pathology, transplantation)
• Caspase 3 (genetics, immunology)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Eosinophils (immunology, pathology)
• Female
• Gene Expression Regulation (immunology)
• Interferon-gamma (genetics, immunology)
• Interleukin-13 (genetics, immunology)
• Interleukin-17 (genetics, immunology)
• Interleukin-4 (genetics, immunology)
• Interleukin-6 (genetics, immunology)
• Membrane Glycoproteins (antagonists & inhibitors, genetics, immunology, pharmacology)
• Mice
• Mice, Inbred BALB C
• OX40 Ligand
• Ovalbumin (administration & dosage)
• Signal Transduction
• Tumor Necrosis Factor Inhibitors
• Tumor Necrosis Factor-alpha (genetics, immunology)
• Tumor Necrosis Factors (genetics, immunology, pharmacology)