Reis L F, Ho Lee T, Vilcek J
Department of Microbiology, New York University Medical Center, New York 10016.
J Biol Chem. 1989 Oct 5;264(28):16351-4.
Medium of untreated human FS-4 foreskin fibroblasts contained a factor which, upon the addition of exogenous tumor necrosis factor (TNF), inhibited encephalomyocarditis virus replication when neither medium alone nor TNF alone were effective. This antiviral activity was abolished by a monoclonal antibody to human interferon (IFN)-beta, suggesting that the active component in the medium from untreated FS-4 cells was IFN-beta, present at subeffective concentrations. In addition, we show that untreated FS-4 cells contain IFN-beta mRNA, demonstrable by the highly sensitive polymerase chain reaction after reverse transcription. Treatment of FS-4 cells with TNF produced an approximately 16-fold increase in the steady-state level of IFN-beta mRNA. Our results support the conclusion that autocrine IFN-beta is secreted by untreated normal fibroblasts and that TNF can enhance the production of autocrine IFN-beta by increasing the level of IFN-beta mRNA. Our study also demonstrates that subeffective concentrations of autocrine IFN-beta, which escape detection in conventional assays, are sufficient to produce a strong synergistic action with TNF.
未处理的人FS-4包皮成纤维细胞的培养基中含有一种因子，当单独的培养基或单独的肿瘤坏死因子（TNF）均无效时，加入外源性TNF后，该因子可抑制脑心肌炎病毒的复制。一种抗人干扰素（IFN）-β单克隆抗体可消除这种抗病毒活性，这表明未处理的FS-4细胞培养基中的活性成分是处于亚有效浓度的IFN-β。此外，我们发现未处理的FS-4细胞含有IFN-β mRNA，逆转录后通过高度灵敏的聚合酶链反应可检测到。用TNF处理FS-4细胞后，IFN-β mRNA的稳态水平增加了约16倍。我们的结果支持以下结论：未处理的正常成纤维细胞分泌自分泌IFN-β，并且TNF可通过增加IFN-β mRNA的水平来增强自分泌IFN-β的产生。我们的研究还表明，在传统检测中未被检测到的亚有效浓度的自分泌IFN-β足以与TNF产生强烈的协同作用。
