Lützow-Holm C, Heyden A, Huitfeldt H S, Brandtzaeg P, Clausen O P
Institute of Pathology, Medical Faculty, National Hospital, Rikshospitalet, University of Oslo, Norway.
Arch Dermatol Res. 1995;287(5):480-7. doi: 10.1007/BF00373432.
Calcitriol (1 alpha,25-dihydroxyvitamin D3) and its analogues are antiproliferative agents which promote epidermal differentiation in vitro, possibly reflecting their modes of action in the treatment of psoriasis. We examined the effect of calcitriol on early and late terminal differentiation in mouse epidermis in vivo using an immunofluorescence assay to detect keratin K1 and filaggrin expression. Pulse labelling with the tymidine analogue 5-bromo-2-deoxyuridine (BrdUrd) was performed by intraperitoneal injection of mice immediately or 16 h after a single topical application of 0.72 nmol calcitriol. The BrdUrd labelling index (LI) and keratin K1 or filaggrin expression of postmitotic cell cohorts were scored by paired immunofluorescence staining for up to 72 h after BrdUrd labelling. Calcitriol induced cell proliferation as shown by a 100% increase in the BrdUrd LI 17 h after application. The onset of keratin K1 expression in the postmitotic period was, however, unchanged in both series after calcitriol treatment. Filaggrin expression appeared earlier after calcitriol treatment than in control epidermis, probably reflecting altered cell kinetics with increased epidermal turnover. The results suggest that calcitriol only influences the later stages of the keratinocyte differentiation programme, possibly secondarily to its hyperproliferative effect.
骨化三醇（1α,25 - 二羟基维生素D3）及其类似物是抗增殖剂，在体外可促进表皮分化，这可能反映了它们在治疗银屑病中的作用方式。我们使用免疫荧光测定法检测角蛋白K1和丝聚蛋白的表达，研究了骨化三醇对体内小鼠表皮早期和晚期终末分化的影响。通过腹腔注射小鼠，在单次局部应用0.72 nmol骨化三醇后立即或16小时，用胸苷类似物5 - 溴 - 2 - 脱氧尿苷（BrdUrd）进行脉冲标记。在BrdUrd标记后长达72小时，通过配对免疫荧光染色对有丝分裂后细胞群的BrdUrd标记指数（LI）以及角蛋白K1或丝聚蛋白表达进行评分。应用骨化三醇后17小时，BrdUrd LI增加100%，表明骨化三醇诱导了细胞增殖。然而，在骨化三醇处理后的两个系列中，有丝分裂后时期角蛋白K1表达的起始时间没有变化。骨化三醇处理后丝聚蛋白表达比对照表皮出现得更早，这可能反映了细胞动力学的改变以及表皮更新增加。结果表明，骨化三醇仅影响角质形成细胞分化程序的后期阶段，可能继发于其增殖作用。
