Voth R, Rossol S, Hess G, Laubenstein H P, Meyer zum Büschenfelde K H, Schröder H C, Bachmann M, Reuter P, Müller W E
I. Medizinische Klinik und Poliklinik, Universität, Mainz, West Germany.
Jpn J Cancer Res. 1988 May;79(5):647-55. doi: 10.1111/j.1349-7006.1988.tb00035.x.
Avarol is a cytostatic and anti-human immunodeficiency virus (HIV) agent. In this study, the avarol caused induction of gamma-interferon (IFN-gamma) in buffy coat cells (human peripheral blood lymphocytes) is demonstrated by immunological and molecular biological techniques. IFN-gamma production was detected after a 24-hr incubation period with avarol; maximal production was obtained after 5 days in the presence of the optimal avarol concentration of 0.75 microgram/ml. Blotting experiments using human IFN-gamma cDNA and beta-actin cDNA containing plasmids showed that in the absence of avarol no IFN-gamma transcripts were present in lymphocytes. Already after a 24-hr incubation with avarol, IFN-gamma gene induction was detected, and maximal induction was found after a 5-day incubation period. The enhanced IFN-gamma production seems to be caused by a change at the transcriptional and/or post-transcriptional level, but not during subsequent nucleocytoplasmic transport of mRNA. This molecular event is specific, at least in relation to the expression of the beta-actin gene. Our studies demonstrate that avarol displays, besides its potential anti-tumor and anti-HIV activity, a potential immunomodulating effect.
阿瓦罗醇是一种细胞抑制剂和抗人类免疫缺陷病毒(HIV)药物。在本研究中,通过免疫学和分子生物学技术证明了阿瓦罗醇可在血沉棕黄层细胞(人外周血淋巴细胞)中诱导γ-干扰素(IFN-γ)。用阿瓦罗醇孵育24小时后检测到IFN-γ的产生;在存在最佳阿瓦罗醇浓度0.75微克/毫升的情况下,5天后获得最大产量。使用含有质粒的人IFN-γ cDNA和β-肌动蛋白cDNA进行的印迹实验表明,在没有阿瓦罗醇的情况下,淋巴细胞中不存在IFN-γ转录本。用阿瓦罗醇孵育24小时后就已检测到IFN-γ基因的诱导,孵育5天后发现诱导作用最大。IFN-γ产生的增强似乎是由转录和/或转录后水平的变化引起的,而不是在随后的mRNA核质转运过程中。这种分子事件是特异性的,至少相对于β-肌动蛋白基因的表达而言。我们的研究表明,阿瓦罗醇除了具有潜在的抗肿瘤和抗HIV活性外,还具有潜在的免疫调节作用。