Maratheftis Christos I, Giannouli Stavroula, Spachidou Maria P, Panayotou George, Voulgarelis Michael
Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece.
Neoplasia. 2007 Dec;9(12):1012-20. doi: 10.1593/neo.07640.
Interferon regulatory factor-1 (IRF-1) is a candidate transcription factor for the regulation of the Toll-like receptor-4 (TLR-4) gene. Using a small interfering RNA-based (siRNA) process to silence IRF-1 gene expression in the leukemic monocytic cell line THP-1, we investigated whether such a modulation would alter TLR-4 expression and activation status in these cells. The siIRF-1 cells expressed elevated levels of TLR-4 mRNA and protein compared to controls by 90% and 77%, respectively. ICAM.1 protein expression and apoptosis levels were increased by 8.35- and 4.25-fold, respectively. The siIRF-1 cells overexpressed Bax mRNA compared to controls. Proteomic analysis revealed upmodulation of the Annexin-II protein in siIRF-1 THP-1 cells. Myelodysplastic syndrome (MDS) patients with an absence of full-length IRF-1 mRNA also overexpressed Annexin-II. It is plausible that this overexpression may lead to the activation of TLR-4 contributing to the increased apoptosis characterizing MDS.
干扰素调节因子-1（IRF-1）是一种用于调节Toll样受体4（TLR-4）基因的候选转录因子。我们采用基于小干扰RNA（siRNA）的方法使白血病单核细胞系THP-1中的IRF-1基因表达沉默，研究这种调节是否会改变这些细胞中TLR-4的表达及激活状态。与对照组相比，siIRF-1细胞中TLR-4的mRNA和蛋白表达水平分别升高了90%和77%。细胞间黏附分子1（ICAM-1）蛋白表达和凋亡水平分别增加了8.35倍和4.25倍。与对照组相比，siIRF-1细胞中Bax mRNA过表达。蛋白质组学分析显示，siIRF-1 THP-1细胞中膜联蛋白II（Annexin-II）蛋白上调。缺乏全长IRF-1 mRNA的骨髓增生异常综合征（MDS）患者也过表达膜联蛋白II。这种过表达可能导致TLR-4激活，从而促使MDS患者出现特征性的凋亡增加，这似乎是合理的。
