Chaidaroglou A, Degiannis D, Koniavitou K, Georgiou S, Tsambaos D
Laboratory of Molecular Immunopathology & Histocompatibility, Onassis Cardiac Surgery Center, Athens, Greece.
Arch Dermatol Res. 1998 Apr;290(4):205-10. doi: 10.1007/s004030050291.
The aim of the present study was to investigate the influence of three different retinoids, isotretinoin, etretinate and acitretin, on the mitogenic response of peripheral blood mononuclear cells (PBMCs) to PHA and PMA in vitro. All three retinoids at high concentrations (10(-4)M) significantly inhibited the mitogenic response of PBMCs to these mitogens. At lower concentrations (10(-5) M and 10(-6) M) none of the three retinoids had any effect on PBMC proliferation in response to PHA. Interestingly, isotretinoin and etretinate significantly enhanced the PMA-induced stimulation of proliferation, whereas acitretin at 10(-5) M failed to influence the mitogenic response to PMA but enhanced it at 10(-6) M. The enhancing effects of retinoids on the proliferative response of PMA-stimulated PBMCs were reversed by rapamycin (10 ng/ml), an immunosuppressant known to inhibit the phorbol ester-induced protein kinase C pathway of lymphocyte activation. In conclusion, our study indicates that retinoids directly trigger the PMA-induced protein kinase C pathway of lymphocyte activation in a concentration-dependent manner. This observation could explain the findings of previous studies showing an in vivo immunopotentiating effect of retinoids on certain immune functions.
本研究的目的是调查三种不同的维甲酸（异维甲酸、阿维A酯和阿维A）对体外培养的外周血单个核细胞（PBMC）对PHA和PMA的促有丝分裂反应的影响。所有三种维甲酸在高浓度（10⁻⁴M）时均显著抑制PBMC对这些有丝分裂原的促有丝分裂反应。在较低浓度（10⁻⁵M和10⁻⁶M）时，三种维甲酸对PBMC对PHA的增殖均无影响。有趣的是，异维甲酸和阿维A酯显著增强了PMA诱导的增殖刺激，而10⁻⁵M的阿维A未能影响对PMA的促有丝分裂反应，但在10⁻⁶M时增强了该反应。雷帕霉素（10 ng/ml）可逆转维甲酸对PMA刺激的PBMC增殖反应的增强作用，雷帕霉素是一种已知可抑制佛波酯诱导的淋巴细胞活化蛋白激酶C途径的免疫抑制剂。总之，我们的研究表明，维甲酸以浓度依赖的方式直接触发PMA诱导的淋巴细胞活化蛋白激酶C途径。这一观察结果可以解释先前研究中显示维甲酸在体内对某些免疫功能具有免疫增强作用的发现。
