ADM: To observe the effects of CD137 - CD137 ligand( CD137L ) interaction on the nuclear factor of activated T — cells, cytoplasmic 1 ( NFATcl ) in apolipoprotein E — knockout ( ApoE-/- ) mice. METHODS: Atherosclerotic plaque model was produced by perivascular carotid collar placement in ApoE -/- mice. In vivo, the expression levels of NFATcl in mouse plaques and lymphocytes were detected by immunohistochemical method and flow cytometry, respectively. In vitro, the expression of NFATcl at mRNA and protein levels in cultured lymphocytes of ApoE-/- mice was measured by RT-PCR and flow cytometry, respectively. RESULTS: In vivo, after CD137 - CD137L signaling pathway was stimulated, the expression of NFATcl was significantly increased in the atherosclerotic plaques and lymphocytes. In vitro, the expression of NFATcl at mRNA and protein levels in cultured leukocytes of ApoE-/- mice was also significantly increased, with the maximal effect exerted by anti - CD137 monoclonal antibody ( mAb ) at the concentration of 20 mg/L, and 24 h after stimulation at any concentration ( P <0. 05 ). Anti - CD137L mAb significantly inhibited the expression of NFATcl at mRNA and protein levels in the lymphocytes of ApoE-/- mice, with the maximal effect exerted by anti — CD137L mAb at the concentration of 20 mg/L, and 24 h after stimulation ( P < 0. 05 ). CONCLUSION: CD137 -CD137L interaction can regulate the expression of NFATcl in ApoE-/- mice.%目的:观察CD137-CD137配体(CD137L)轴对载脂蛋白E基因敲除(ApoE-/-)小鼠活化T细胞核因子胞浆1型(NFATc1)表达的影响.方法:ApoE-/-小鼠动脉粥样斑块模型采用颈动脉硅胶圈植入法;分别采用免疫组化及流式细胞术检测小鼠颈动脉斑块及淋巴细胞NFATc1表达;分别应用RT-PCR和流式细胞技术检测体外培养的小鼠淋巴细胞NFATc1 mRNA和蛋白表达.结果:在体情况下应用anti-CD137特异性刺激CD137-CD137L轴后,ApoE-/-小鼠斑块及脾脏中淋巴细胞NFATc1表达增加;体外培养的淋巴细胞刺激CD137-CD137L轴后,淋巴细胞NFATc1 mRNA和蛋白表达明显上调,anti-CD137刺激浓度以20 mg/L时作用最强,作用24 h最明显(P<0.05).应用Anti-CD137L特异性阻断CD137-CD137L轴能明显抑制NFATc1 mRNA及蛋白表达,浓度在20 mg/L时抑制最强,时间为24 h后抑制最佳(P<0.05).结论:ApoE-/-小鼠体内NFATc1的表达受CD137-CD137L轴调控.
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