Inhibition of the CD8+ T cell-mediated cytotoxicity reaction by hypericin: potential for treatment of T cell-mediated diseases.
Inhibition of the CD8+ T cell-mediated cytotoxicity reaction by hypericin: potential for treatment of T cell-mediated diseases.
复制标题
金丝桃素抑制 CD8 T 细胞介导的细胞毒性反应：治疗 T 细胞介导的疾病的潜力。
DOI：
10.1093/intimm/12.4.479
复制
发表时间：
2000
影响因子：
4.4
通讯作者：
Mandel,M
中科院分区：
文献类型：
--
作者：
Lavie,G;Meruelo,D;Aroyo,K;Mandel,M
小鼠CD8 T淋巴细胞的细胞毒性反应被纳米摩尔浓度的金丝桃素强烈抑制，金丝桃素是一种具有光动力学性质的亲脂二蒽醌。细胞毒性T淋巴细胞（CTL）诱导的靶细胞凋亡，以及这些细胞的细胞溶解颗粒的胞吐，在反应开始时被金丝桃素消融，而不影响CTL的活力。细胞溶解的抑制发生在没有光照射的情况下，而光照射是光敏化所必需的。结果表明，金丝桃素的作用主要针对CTL；然而，金丝桃素也能阻止重组肿瘤坏死因子(TNF)-α诱导的小鼠l细胞凋亡。由于金丝桃素是一种已知的蛋白激酶C、MAP激酶和至少一种其他酪氨酸激酶的抑制剂，这种抑制活性可能在ctl诱导的细胞毒性下调中发挥作用。此外，我们的研究表明，金丝桃素的作用诱导CTL中与低密度膜相关的磷脂的快速去磷酸化，但不与细胞毒性颗粒的膜相关。金丝桃素干扰细胞毒性的能力可能使其在治疗T细胞介导的疾病中有用。
The cytotoxicity reaction of murine CD8 T lymphocytes has been found to be strongly inhibited by nanomolar concentrations of hypericin, a lipophilic dianthraquinone with photodynamic properties. Cytotoxic T lymphocyte (CTL)-induced target cell apoptosis, as well as exocytosis of cytolytic granules from these cells, were ablated by hypericin, administered at the onset of the reaction, without affecting CTL viability. The inhibition of cytolysis occurred without the light irradiation which is essential for photosensitization. The findings suggest that the action of hypericin targets the effector CTL; however, apoptosis induced in murine L-cells with recombinant tumor necrosis factor (TNF)-α was also prevented by hypericin. Since hypericin is a known inhibitor of protein kinase C, MAP kinase and at least one other tyrosine kinase, this inhibitory activity could play a role in the down-modulation of CTL-induced cytotoxicity. Furthermore, our studies show that the action of hypericin induces rapid dephosphorylation of phospholipids associated with low-density membranes in CTL, but not with membranes of the cytotoxic granules. The ability of hypericin to interfere with cytotoxicity may render it useful in the treatment of T cell-mediated diseases.