A novel anti‐inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology
A novel anti‐inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology
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一种治疗皮肤病的新型抗炎药SDZ ASM 981：体外药理学
DOI：
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发表时间：
1999
影响因子：
10.3
通讯作者：
G. Zenke
中科院分区：
文献类型：
--
作者：
M. Grassberger;T. Baumruker;A. Enz;P. Hiestand;T. Hultsch;F. Kalthoff;W. Schuler;M. Schulz;F. Werner;A. Winiski;B. Wolff;G. Zenke
SDZ ASM 981是一种新型子囊霉素大环内酰胺衍生物，在过敏性接触性皮炎动物模型中具有较高的抗炎活性，局部应用后对特应性皮炎、过敏性接触性皮炎和银屑病具有临床疗效。在这里，我们报告了这种有前途的新药的体外活性。SDZ ASM 981在抗原特异性或非特异性刺激后抑制人T细胞增殖。在抗原特异性刺激从特应性皮炎患者皮肤分离的人辅助性T细胞克隆后，其下调Th 1 [白细胞介素（IL）-2，干扰素-γ]和Th 2（IL-4，IL-10）型细胞因子的产生。SDZ ASM 981抑制人T细胞系Jurkat中与人IL-2启动子偶联的报告基因的佛波醇肉豆蔻酸酯/植物血凝素刺激的转录，以及鼠肥大细胞系CPII中与人肿瘤坏死因子（TNF）-α启动子偶联的报告基因的IgE/抗原介导的转录。然而，在通过FcγRIII受体刺激后，其不影响鼠树突状细胞系（DC 18 RGA）中人TNF-α启动子控制的报告基因转录。SDZ ASM 981还可防止肥大细胞释放预先形成的促炎介质，如小鼠细胞系CPII在IgE/抗原刺激后所示。总之，这些结果表明SDZ ASM 981是体外T细胞和肥大细胞产生促炎细胞因子的特异性抑制剂。
SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti‐inflammatory activity in animal models of allergic contact dermatitis and shows clinical efficacy in atopic dermatitis, allergic contact dermatitis and psoriasis, after topical application. Here we report on the in vitro activities of this promising new drug. SDZ ASM 981 inhibits the proliferation of human T cells after antigen‐specific or non‐specific stimulation. It downregulates the production of Th1 [interleukin (IL)‐2, interferon‐γ] and Th2 (IL‐4, IL‐10) type cytokines after antigen‐specific stimulation of a human T‐helper cell clone isolated from the skin of an atopic dermatitis patient. SDZ ASM 981 inhibits the phorbol myristate acetate/phytohaemagglutinin‐stimulated transcription of a reporter gene coupled to the human IL‐2 promoter in the human T‐cell line Jurkat and the IgE/antigen‐mediated transcription of a reporter gene coupled to the human tumour necrosis factor (TNF)‐α promoter in the murine mast‐cell line CPII. It does not, however, affect the human TNF‐α promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcγRIII receptor. SDZ ASM 981 also prevents the release of preformed pro‐inflammatory mediators from mast cells, as shown in the murine cell line CPII after stimulation with IgE/antigen. In summary, these results demonstrate that SDZ ASM 981 is a specific inhibitor of the production of pro‐inflammatory cytokines from T cells and mast cells in vitro.
影响因子：
2.9
作者：
LIU, J;ALBERS, MW;SCHREIBER, SL
通讯作者：
SCHREIBER, SL
影响因子：
6.5
作者：
UYEMURA, K;YAMAMURA, M;NICKOLOFF, BJ
通讯作者：
NICKOLOFF, BJ