title: OX40-OX40L interaction promotes proliferation and activation of lymphocytes via NFATc1 in ApoE-deficient mice.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggest that OX40-OX40L interaction promotes the proliferation and activation of lymphocytes through NFATc1.
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China. yanjinchuan@hotmail.com
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
authors.forename: Hongling
authors.initials: H
authors.lastname: Su
authors.forename: Liangjie
authors.initials: L
authors.lastname: Xu
authors.forename: Cuiping
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000378:metabolism*; D053278:OX40 Ligand / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011485:Protein Binding; D053262:Receptors, OX40 / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D050778:NFATC Transcription Factors; D053278:OX40 Ligand; D053262:Receptors, OX40