Anderson R, Lukey P T, Dippenaar U, Eftychis H A, Findlay G H, Wooten M W, Nel A E
Department of Medical Microbiology, University of Pretoria, Republic of South Africa.
Br J Dermatol. 1987 Oct;117(4):405-18. doi: 10.1111/j.1365-2133.1987.tb04920.x.
Dithranol (0.01-1 micrograms/ml), but not the auto-oxidized form, caused a dose-related enhancement of the generation of reactive oxidants by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. At the same concentrations dithranol inhibited both PMNL migration to leukoattractants and mitogen-stimulated mononuclear leukocyte (MNL) proliferation. Catalase (50-100 units/ml) protected both PMNL migration and MNL proliferation from dithranol whilst ascorbate and cysteine (1 mM), which maintain dithranol in the biologically active reduced state, potentiated the inhibition. To establish the molecular mechanism of the pro-oxidative activity of dithranol its effects on cytosolic protein kinase C (PKC) activity were investigated. Dithranol caused a dose-related activation of PKC by apparent substitution for 1,2-diolein. These results demonstrate that dithranol, but not its auto-oxidation products, activates PKC which in turn initiates the generation of reactive oxidants by PMNL. Since reactive oxidants are immunosuppressive the therapeutic mechanisms of dithranol may be related to pro-oxidative interactions of this agent with skin phagocytes.
地蒽酚（0.01 - 1微克/毫升），而非其自动氧化形式，在体外可导致白细胞趋化剂激活的多形核白细胞（PMNL）产生剂量相关的活性氧增强。在相同浓度下，地蒽酚抑制PMNL向白细胞趋化剂的迁移以及丝裂原刺激的单核白细胞（MNL）增殖。过氧化氢酶（50 - 100单位/毫升）可保护PMNL迁移和MNL增殖免受地蒽酚影响，而抗坏血酸和半胱氨酸（1毫摩尔）可使地蒽酚维持在生物活性还原状态，增强这种抑制作用。为确定地蒽酚促氧化活性的分子机制，研究了其对胞质蛋白激酶C（PKC）活性的影响。地蒽酚通过明显替代1,2 - 二油精导致PKC的剂量相关激活。这些结果表明，地蒽酚而非其自动氧化产物激活PKC，进而引发PMNL产生活性氧。由于活性氧具有免疫抑制作用，地蒽酚的治疗机制可能与其与皮肤吞噬细胞的促氧化相互作用有关。
