Franssen M E J, Smit J V, Van Erp P E J, Van De Kerkhof P C M
Department of Dermatology, University Medical Centre St Radboud Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Br J Dermatol. 2003 Sep;149(3):506-12. doi: 10.1046/j.1365-2133.2003.05474.x.
A new retinoid, bexarotene (Targretin), was recently investigated in a large multicentre trial for its efficacy and safety in psoriasis. Bexarotene is a novel retinoid X receptor (RXR)-selective ligand.
The aim was to study the effect of bexarotene in psoriasis by analysing markers for epidermal differentiation, proliferation and inflammation in epidermal single cell suspensions from lesions of patients with psoriasis treated with various doses of bexarotene.
Thirty-four patients with moderate to severe plaque psoriasis participated in this study and were assigned in sequence to four different dose regimens: 0.5, 1, 2 and 3 mg kg-1 once daily. Before and after 12 weeks of bexarotene treatment, punch biopsies were taken from lesional skin from which epidermal single cell suspensions were prepared using an optimized thermolysin protocol. A sum of scores was determined for each biopsy site, based on a four-point scale for erythema, induration and desquamation. An improved multiparameter flow cytometric assay was used that enabled simultaneous assessment of epidermal proliferation, various aspects of differentiation and epidermal inflammation. The following variables were measured simultaneously: relative DNA content, relative cell size, keratin (K) 10, K6 and vimentin expression.
The psoriasis area and severity index (PASI) and sum of scores for the individual psoriatic lesion each showed a statistically significant decrease of 28% after 12 weeks of bexarotene treatment (P < 0.001). However, no significant dose-response effect was found. The total percentage of K10+ cells showed a significant increase of 43% (P < 0.01). The total population of K6 expressing cells did not show significant changes. Regarding the subpopulations of K6 single, K10 single and K6 and 10 co-expressing cells, a significant increase of 77% was seen in the K10+ K6- cells (P < 0.05), a significant decrease of 33% in K10- K6+ cells (P < 0.01), and no significant changes in the remaining population of K10+ K6+ cells. After 12 weeks of treatment with bexarotene no significant changes in epidermal proliferation and inflammation were shown.
The present study indicates a direct effect of RXR activation by bexarotene on the transition of proliferation-associated keratinization into normal keratinization. Although no direct effect of bexarotene on DNA content in the total K10- cells was shown, further studies on subpopulations within the germinative layer such as stem cells and transit amplifying cells might be worthwhile.
一种新型维甲酸——贝沙罗汀（他扎罗汀），最近在一项大型多中心试验中对其治疗银屑病的疗效和安全性进行了研究。贝沙罗汀是一种新型维甲酸X受体（RXR）选择性配体。
通过分析用不同剂量贝沙罗汀治疗的银屑病患者皮损处表皮单细胞悬液中表皮分化、增殖和炎症的标志物，研究贝沙罗汀对银屑病的影响。
34例中度至重度斑块状银屑病患者参与本研究，并依次分配到四种不同剂量方案：0.5、1、2和3mg kg-1每日一次。在贝沙罗汀治疗12周前后，从皮损处取打孔活检组织，使用优化的嗜热菌蛋白酶方案制备表皮单细胞悬液。根据红斑、硬结和脱屑的四分制量表，为每个活检部位确定一个总分。采用一种改进的多参数流式细胞术检测方法，能够同时评估表皮增殖、分化的各个方面和表皮炎症。同时测量以下变量：相对DNA含量、相对细胞大小、角蛋白（K）10、K6和波形蛋白表达。
贝沙罗汀治疗12周后，银屑病面积和严重程度指数（PASI）以及单个银屑病皮损的总分均显示出统计学上显著的28%下降（P < 0.001）。然而，未发现显著的剂量反应效应。K10+细胞的总百分比显著增加了43%（P < 0.01）。表达K6的细胞总数没有显著变化。关于K6单表达、K10单表达以及K6和10共表达细胞的亚群，K10+ K6-细胞显著增加了77%（P < 0.
