Troglitazone improves psoriasis and normalizes models of proliferative skin disease -: Ligands for peroxisome proliferator-activated receptor-γ inhibit keratinocyte proliferation
Troglitazone improves psoriasis and normalizes models of proliferative skin disease -: Ligands for peroxisome proliferator-activated receptor-γ inhibit keratinocyte proliferation
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DOI：
10.1001/archderm.136.5.609
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发表时间：
2000-05-01
影响因子：
--
通讯作者：
Kurtz, TW
中科院分区：
文献类型：
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作者：
Ellis, CN;Varani, J;Kurtz, TW
背景：银屑病通常使用激活糖皮质激素、类维生素A和维生素D核激素受体的药物进行治疗。过氧化物酶体增殖物激活受体-γ（PPARγ）是一种相关的核激素受体，可以被其配体（包括噻唑烷二酮类）激活。目的：评估曲格列酮（一种目前用于治疗糖尿病的噻唑烷二酮类药物）治疗是否对治疗银屑病有影响。血糖正常患者的银屑病以及 PPAR γ 配体是否对银屑病模型有影响。设计：银屑病患者曲格列酮的开放标签给药以及药物在银屑病细胞、器官和移植模型中的作用评价。地点：大学和社区医院门诊部和大学实验室。患者：慢性、稳定斑块型银屑病患者和对照受试者。 5 名银屑病患者接受曲格列酮治疗（无人退出）； 10 名不同的未经治疗的患者和 10 名对照者提供了组织样本。干预措施：银屑病患者口服不同剂量的曲格列酮治疗；此外，在银屑病模型中使用曲格列酮、环格列酮和 15-脱氧-Delta-12,14-前列腺素 J(2)。主要结果指标：研究者确定的患者临床结果以及模型中的细胞计数和组织学证据。结果：所有患者的银屑病在曲格列酮治疗期间均得到显着改善。过氧化物酶体增殖物激活受体-γ 在人角质形成细胞中表达； PPAR γ 配体抑制培养物中正常和银屑病人类角质形成细胞的增殖。曲格列酮治疗使器官培养中银屑病皮肤的组织学特征正常化，并减少严重联合免疫缺陷小鼠和人银屑病皮肤移植模型中银屑病的表皮增生（P
Background: Psoriasis is often treated with agents that activate nuclear hormone receptors for glucocorticoids, retinoids, and vitamin D. The peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a related nuclear hormone receptor that can be activated by its ligands, including the thiazolidinediones.Objective: To assess whether treatment with troglitazone, a currently available thiazolidinedione used to treat diabetes mellitus, has an effect on psoriasis in normoglycemic patients and whether ligands for PPAR gamma have an effect on models of psoriasis.Design: Open-label administration of troglitazone in patients with psoriasis and evaluation of drug actions in cellular, organ, and transplant models of psoriasis.Setting: University and community hospital outpatient departments and university laboratories.Patients: Patients with chronic, stable plaque psoriasis and control subjects. Five patients with psoriasis received troglitazone (none withdrew); 10 different untreated patients and 10 controls provided tissue samples.Interventions: Oral troglitazone therapy at various dosages in patients with psoriasis; also, use of troglitazone, ciglitazone, and 15-deoxy-Delta-12,14-prostaglandin J(2) in psoriasis models.Main Outcome Measures: Investigator-determined clinical results in patients and cell counts and histological evidence in models.Results: All patients' psoriasis improved substantially during troglitazone therapy. Peroxisome proliferator-activated receptor-gamma was expressed in human keratinocytes; ligands for PPAR gamma inhibited the proliferation of normal and psoriatic human keratinocytes in culture. Troglitazone treatment normalized the histological features of psoriatic skin in organ culture and reduced the epidermal hyperplasia of psoriasis in the severe combined immunodeficient mouse and human skin transplant model of psoriasis (P