Journal Article

OX40-OX40L Interaction Promotes Proliferation and Activation of Lymphocytes via NFATc1 in ApoE-Deficient Mice

Xu, Liangjie, Su, Hongling, Yan, Jinchuan, Wang, Cuiping

2013

Overview

Our previous studies have shown that OX40-OX40L interaction regulates the expression of nuclear factor of activated T cells c1(NFATc1) in ApoE(-/-) mice during atherogenesis. The aim of this study was to investigate whether OX40-OX40L interaction promotes Th cell activation via NFATc1 in ApoE(-/-) mice. The lymphocytes isolated from spleen of ApoE (-/-) mice were cultured with anti-CD3 mAb in the presence or absence of anti-OX40 or anti-OX40L antibodies. The expression of NFATc1 mRNA and protein in isolated lymphocytes were measured by real time PCR (RT-PCR) and flow cytometry (FCM), respectively. The proliferation of lymphocytes was analyzed by MTT method,and the expression of IL-2, IL-4 and IFN-γ in the cultured cells and supernatant were measured by RT-PCR and enzyme-linked immunosorbent assary (ELISA), respectively. After stimulating OX40-OX40L signal pathway, the expression of NFATc1 and the proliferation of leukocytes were significantly increased. Anti-OX40L suppressed the expression of NFATc1 in lymphocytes of ApoE-/- mice. Anti-OX40L or the NFATc1 inhibitor (CsA) markedly suppressed the cell proliferation induced by anti-OX40. Moreover, the expression of IL-2 and IFN-γ was increased in lymphocytes induced by OX40-OX40L interaction. Blocking OX40-OX40L interaction or NFATc1 down-regulated the expression of IL-2 and IFN-γ, but didn't alter the expression of IL-4 in supernatants. These results suggest that OX40-OX40L interaction promotes the proliferation and activation of lymphocytes through NFATc1.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Antibodies / Antigens / Apolipoprotein E / Apolipoproteins / Apolipoproteins E - deficiency / Arthritis / Atherogenesis / Atherosclerosis / Atherosclerosis - genetics / Atherosclerosis - metabolism / Atherosclerosis - pathology / Biology / Cardiology / CD3 antigen / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - metabolism / Cell activation / Cell culture / Cell growth / Cell proliferation / Cytokines / Cytometry / Enzyme-linked immunosorbent assay / Flow cytometry / Gene expression / Interferon / Interleukin 2 / Interleukin 4 / Laboratory animals / Leukocytes / Ligands / Lymphocyte Activation - genetics / Lymphocyte Activation - immunology / Lymphocytes / Lymphocytes - immunology / Lymphocytes - metabolism / Male / Medicine / Mice / Mice, Knockout / Monoclonal antibodies / mRNA / NF-AT protein / NFATC Transcription Factors - metabolism / OX40 Ligand - metabolism / Ox40L protein / Pathogenesis / Plaque, Atherosclerotic - pathology / Polymerase chain reaction / Protein Binding / Receptors, OX40 - metabolism / RNA / Rodents / Signal transduction / Spleen / T cells / Thermal cycling / Time Factors / Transcription factors / Tumor necrosis factor / White blood cells / γ-Interferon