Reichrath J, Müller S M, Kerber A, Baum H P, Bahmer F A
Department of Dermatology, University of the Saarland, Germany.
J Am Acad Dermatol. 1997 Jan;36(1):19-28. doi: 10.1016/s0190-9622(97)70320-7.
The biologically active vitamin D analog calcipotriol is effective and safe in the topical treatment of psoriasis, but its exact mechanism of action is unknown.
We investigated expression of 1,25-dihydroxyvitamin D3 receptors, markers for inflammation (CD1a, CD4, CD8, CD11b, CD15; NAP-1/interleukin-8; 55 kd tumor necrosis factor-receptor; intercellular adhesion molecule-1; HLA-DR), proliferation (proliferating cell nuclear antigen, Ki-67), and differentiation (transglutaminase K; involucrin; cytokeratin 16) in psoriatic skin during topical calcipotriol treatment.
For immunohistochemical staining we used the labeled avidin-biotin technique on cryostat-cut sections.
We found a significant increase of 1,25-dihydroxyvitamin D3 receptor expression in epidermal basal keratinocytes of lesional psoriatic skin during calcipotriol treatment. In all patients analyzed, effects on proliferation and differentiation of epidermal keratinocytes were stronger than effects on dermal inflammation. Effects on inflammation were more pronounced in the epidermal than in the dermal compartment.
Our findings indicate that analogs of 1,25-dihydroxyvitamin D3 upregulate their corresponding receptor in human keratinocytes in vivo. This mechanism may be important in the therapeutic efficacy of vitamin D analogs in psoriasis. The differential therapeutic effects in the epidermal and dermal skin compartments may be due to a reduced bioavailability of calcipotriol in the dermal compartment.
生物活性维生素D类似物卡泊三醇在银屑病局部治疗中有效且安全，但其确切作用机制尚不清楚。
我们研究了局部应用卡泊三醇治疗期间银屑病皮肤中1,25 - 二羟维生素D3受体、炎症标志物（CD1a、CD4、CD8、CD11b、CD15；NAP - 1/白细胞介素 - 8；55kd肿瘤坏死因子受体；细胞间黏附分子 - 1；HLA - DR）、增殖标志物（增殖细胞核抗原、Ki - 67）和分化标志物（转谷氨酰胺酶K；内披蛋白；细胞角蛋白16）的表达情况。
我们采用标记抗生物素蛋白 - 生物素技术对冰冻切片进行免疫组织化学染色。
我们发现卡泊三醇治疗期间，银屑病皮损皮肤的表皮基底角质形成细胞中1,25 - 二羟维生素D3受体表达显著增加。在所有分析的患者中，对表皮角质形成细胞增殖和分化的影响强于对真皮炎症的影响。对炎症的影响在表皮比在真皮更明显。
我们的研究结果表明，1,25 - 二羟维生素D3类似物在体内可上调人角质形成细胞中其相应受体的表达。这一机制可能对维生素D类似物治疗银屑病的疗效很重要。表皮和真皮皮肤层的不同治疗效果可能是由于卡泊三醇在真皮层的生物利用度降低所致。
