中华皮肤科杂志

• 论著 • 上一篇    下一篇

来氟米特对地蒽酚诱导炎症因子表达的调控

冯华, 李新宇, 郑家润   

  1. 中国医学科学院、中国协和医科大学皮肤病医院 南京 210042
  • 收稿日期:2005-04-05 出版日期:2006-02-15 发布日期:2006-02-15

Regulation of anthralin-induced cytokine expression in keratinocytes by leflunomide

FENG Hua, LI Xin-yu, ZHENG Jia-run   

  1. Department of Pharmaceutical Research, Institute of Dermatology, Chinese Academy of Medical Sciences &
    Peking Union Medical College, Nanjing 210042, China
  • Received:2005-04-05 Online:2006-02-15 Published:2006-02-15

摘要: 目的 探讨利用角质形成细胞核因子(NF)-κB抑制药物来氟米特对地蒽酚诱导角质形成细胞所表达的炎症因子进行调控的可能性.方法 采用蛋白印迹法检测NF-κB抑制蛋白α(IκBα)表达的变化,以此反映药物对细胞NF-κB活性的影响.使用MTT法检测药物处理后细胞增殖活力的改变,RT-PCR检测药物对炎症因子mRNA表达的影响.结果 来氟米特可显著抑制地蒽酚对角质形成细胞HaCaT株IκBα蛋白的降解作用,也即抑制地蒽酚对NF-κB信号途径的活化.实验表明,NF-κB活化与地蒽酚抑制增殖的作用无关.实验显示,在相应的剂量范围内,来氟米特可以显著抑制地蒽酚所诱导的炎症因子细胞间黏附分子-1(ICAM-1)mRNA的表达,并呈剂量依赖性.结论 NF-κB活化并未参与抗银屑病外用药物地蒽酚对增殖的抑制作用.

关键词: 来氟米特, 地蒽酚, NF-κB, 角蛋白细胞, 胞间黏附分子1

Abstract: Objective To determine whether leflunomide could control the proinflammatory cytokine expression induced by anthralin via inhibiting the activation of nuclear factor κB (NF-κB).Methods The expression of NF-κB inhibitory protein α (IκBα),was analyzed by using Western blot method.MTT assay and RT-PCR were used to assess the proliferating activity and mRNA expression of intercellular adhesion molecule-1 (ICAM-1) of HaCaT keratinocytes,respectively.Results Leflunomide inhibited the degradation of IκBα by anthralin,i.e.the activation of NF-κB signaling pathway,in a dose-dependent manner.The inhibition of keratinocyte growth by anthralin did not correlate with the activation of NF-κB.Under the experimental conditions used,leflunomide was shown to be able to significantly inhibit the over-expression of ICAM-1 on keratinocytes induced by anthralin;this inhibition occurred in a dose dependent manner.Conclusions Growth inhibition by topical anti-psoriatic medication anhtralin is unrelated to the NF-κB-dependent signaling pathway,and leflunomide can control ICAM-1 expression induced by anthralin via inhibiting the activation of NF-κB.

Key words: Intercellular adhesion molecule-1, NF-kappa B, Keratinocytes, Leflunomide, Anthralin