Stein M, Bernd A, Ramirez-Bosca A, Kippenberger S, Holzmann H
Zentrum der Dermatologie und Venerologie, Johann Wolfang Goethe-University, Frankfurt/Main, Germany.
Arzneimittelforschung. 1997 Nov;47(11):1266-70.
There are only few objective in vitro methods available for the testing of anti-inflammatory pharmaceutical products. One possibility is in the stimulation of cytokine production in cultivated human keratinocytes by UV light and the subsequent testing of suppressing activities. From the dermatological aspect the interleukins 6 and 8 are especially interesting because they are elevated in psoriatic skin. In the present work three glucocorticoids were tested in cultures of normal human keratinocytes and in the permanent keratinocyte cell line HaCaT. Both cell species produced IL-6 and IL-8 spontaneously, albeit in very small amounts. After UV irradiation the interleukin production increased in a dose dependent manner. The IL-6 and IL-8 induction could be suppressed by each of the glucocorticoids tested. The thymidine incorporation rate of the cells was not affected by the glucocorticoids indicating that the observed suppression of cytokine induction was not the result of a generalised cell damage. The response of both HaCaT keratinocytes and primary human keratinocytes to UV irradiation and glucocorticoid application was similar indicating the possible use of the generally available HaCaT cells for the pharmacological testing of anti-inflammatory activities in vitro.
目前仅有几种客观的体外方法可用于测试抗炎药物产品。一种方法是通过紫外线刺激培养的人角质形成细胞中细胞因子的产生,随后测试其抑制活性。从皮肤病学角度来看,白细胞介素6和8特别值得关注,因为它们在银屑病皮肤中含量升高。在本研究中,对三种糖皮质激素在正常人角质形成细胞培养物和永久性角质形成细胞系HaCaT中进行了测试。两种细胞类型均自发产生IL-6和IL-8,尽管产量很少。紫外线照射后,白细胞介素的产生呈剂量依赖性增加。所测试的每种糖皮质激素均可抑制IL-6和IL-8的诱导。细胞的胸苷掺入率不受糖皮质激素的影响,这表明观察到的细胞因子诱导抑制不是普遍细胞损伤的结果。HaCaT角质形成细胞和原代人角质形成细胞对紫外线照射和糖皮质激素应用的反应相似,这表明通常可用的HaCaT细胞可能用于体外抗炎活性的药理学测试。