Hegemann L, Fruchtmann R, van Rooijen L A, Müller-Peddinghaus R, Mahrle G
Department of Dermatology, University of Köln, Federal Republic of Germany.
Arch Dermatol Res. 1992;284(3):179-83. doi: 10.1007/BF00372713.
In psoriatic patients, anthralin is known to attenuate lesional inflammation, but often generates perilesional dermatitis. This phenomenon is well reflected by the contrasting action of anthralin on human leukocytes. The release of reactive oxygen species (ROS) is inhibited by anthralin in phorbol ester-activated leukocytes, whereas anthralin directly induces this cellular response in unstimulated cells. In order to elaborate further the underlying mechanisms, we compared the kinetics of anthralin and different well-characterized stimuli, including the phorbol ester, phorbol-12-myristate-13-acetate, in this test system. Compared with standard stimuli, anthralin only marginally induced the release of ROS from human leukocytes and displayed different kinetics. Protein kinase C (PKC), the major cellular phorbol ester receptor, is considered to be involved in the regulation of this cellular response. Furthermore, its involvement in the pathophysiology of psoriasis has been suggested. Therefore, we also investigated the effects of anthralin on purified PKC. Anthralin was found to inhibit the enzyme activity in a dose-dependent manner but not to display any stimulatory effects. The present results provide first evidence that the therapeutic activity of anthralin, at least in part, might be mediated by inhibition of PKC.
在银屑病患者中，已知蒽林可减轻皮损炎症，但常引发皮损周围皮炎。蒽林对人类白细胞的不同作用很好地反映了这一现象。在佛波酯激活的白细胞中，蒽林可抑制活性氧（ROS）的释放，而在未受刺激的细胞中，蒽林可直接诱导这种细胞反应。为了进一步阐述其潜在机制，我们在该测试系统中比较了蒽林与不同的、特征明确的刺激物（包括佛波酯、佛波醇-12-肉豆蔻酸酯-13-乙酸酯）的动力学。与标准刺激物相比，蒽林仅轻微诱导人类白细胞释放ROS，且表现出不同的动力学。蛋白激酶C（PKC）是主要的细胞佛波酯受体，被认为参与这种细胞反应的调节。此外，有人提出其参与银屑病的病理生理学过程。因此，我们还研究了蒽林对纯化的PKC的影响。发现蒽林以剂量依赖的方式抑制该酶的活性，但未表现出任何刺激作用。目前的结果首次证明，蒽林的治疗活性至少部分可能是由抑制PKC介导的。
