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Publication : OX40-OX40L interaction promotes proliferation and activation of lymphocytes via NFATc1 in ApoE-deficient mice.

First Author  Yan J Year  2013
Journal  PLoS One Volume  8
Issue  4 Pages  e60854
PubMed ID  23593329 Mgi Jnum  J:200581
Mgi Id  MGI:5508875 Doi  10.1371/journal.pone.0060854
Citation  Yan J, et al. (2013) OX40-OX40L interaction promotes proliferation and activation of lymphocytes via NFATc1 in ApoE-deficient mice. PLoS One 8(4):e60854
abstractText  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. METHODS AND 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-gamma 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-gamma was increased in lymphocytes induced by OX40-OX40L interaction. Blocking OX40-OX40L interaction or NFATc1 down-regulated the expression of IL-2 and IFN-gamma, but didn't alter the expression of IL-4 in supernatants. CONCLUSION: These results suggest that OX40-OX40L interaction promotes the proliferation and activation of lymphocytes through NFATc1.
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