Savici D, He B, Geist L J, Monick M M, Hunninghake G W
Department of Medicine, Veterans Affairs Center, Iowa City, Iowa.
Exp Lung Res. 1994 Nov-Dec;20(6):613-25. doi: 10.3109/01902149409031740.
Silica causes release of tumor necrosis factor (TNF) from mononuclear phagocytes. One hypothesis is that silica increases TNF production, in part, by upregulating the TNF gene. To evaluate this hypothesis, THP-1 cells (a myelomonocytic cell line) were exposed to various amounts of silica and then the TNF gene transcription was evaluated. In this study silica caused a dose-dependent increase in TNF mRNA and the peak response occurred at 3 h following stimulation. A transient transfection assay also showed that silica upregulated expression of a TNF CAT construct in THP-1 cells. Furthermore, a nuclear run-on assay demonstrated that silica particles induce increased TNF gene transcription in exposed cells. THP-1 cells cultured for various periods of time in the presence of silica released TNF into the cell supernatants. These studies show that silica can upregulate the TNF gene, which results in the release of TNF protein from the cells.
二氧化硅可导致单核吞噬细胞释放肿瘤坏死因子（TNF）。一种假说认为，二氧化硅部分通过上调TNF基因来增加TNF的产生。为了评估这一假说，将THP - 1细胞（一种骨髓单核细胞系）暴露于不同量的二氧化硅中，然后评估TNF基因转录情况。在本研究中，二氧化硅导致TNF mRNA呈剂量依赖性增加，刺激后3小时出现峰值反应。瞬时转染试验还表明，二氧化硅上调了THP - 1细胞中TNF CAT构建体的表达。此外，核转录分析表明，二氧化硅颗粒可诱导暴露细胞中TNF基因转录增加。在二氧化硅存在下培养不同时间的THP - 1细胞将TNF释放到细胞上清液中。这些研究表明，二氧化硅可上调TNF基因，从而导致细胞释放TNF蛋白。
