OX40-OX40L interaction promotes proliferation and activation of lymphocytes via NFATc1 in ApoE-deficient mice.
OX40-OX40L interaction promotes proliferation and activation of lymphocytes via NFATc1 in ApoE-deficient mice.
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OX40-OX40L 相互作用通过 NFATc1 在 ApoE 缺陷小鼠中促进淋巴细胞增殖和活化
DOI：
10.1371/journal.pone.0060854
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Yan J;Su H;Xu L;Wang C
我们以前的研究表明，在动脉粥样硬化形成过程中，OX40-OX40L相互作用调节ApoE−/−小鼠活化T细胞核因子C1NFATc1的表达。本研究的目的是探讨OX40-OX40L相互作用是否通过NFATc1促进载脂蛋白E−/−小鼠Th细胞的活化。从载脂蛋白E−/−小鼠的脾中分离淋巴细胞，在有或无抗OX40或抗OX40L抗体的情况下，用抗CD3mAb进行培养。分别用实时定量聚合酶链式反应(RT-PCR)和流式细胞仪(FCM)检测分离淋巴细胞中NFATc1基因和蛋白的表达。用四甲基偶氮唑盐比色法检测淋巴细胞增殖活性，用逆转录聚合酶链式反应检测培养细胞和培养上清液中IL-2、IL-4和干扰素-γ的表达。刺激OX40-OX40L信号通路后，NFATc1的表达和白细胞的增殖明显增加。抗OX40L可抑制载脂蛋白E−/−小鼠淋巴细胞中NFATc1的表达。抗OX40L或NFATc1抑制剂(CsA)显著抑制抗OX40诱导的细胞增殖。此外，OX40-OX40L相互作用诱导的淋巴细胞IL-2和干扰素-γ的表达增加。阻断OX40-OX40L相互作用或NFATc1可下调IL-2和干扰素-γ的表达，但不改变上清液中IL-4的表达。这些结果表明，OX40-OX40L相互作用通过NFATc1促进淋巴细胞的增殖和激活。
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.