ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-κB to regulate the inducible nitric-oxide synthase gene

作     者：Rudders, S Gaspar, J Madore, R Voland, C Grall, F Patel, A Pellacani, A Perrella, MK Libermann, TA Oettgen, P 

作者机构：Harvard Univ Sch Med Inst Med Boston MA 02115 USA Beth Israel Deaconess Med Ctr New England Baptist Bone & Joint Inst Boston MA 02115 USA Beth Israel Deaconess Med Ctr Div Cardiol Boston MA 02115 USA Brigham & Womens Hosp Dept Med Boston MA 02115 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2001年第276卷第5期

页      面：3302-3309页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NCI NIH HHS [R01/CA76323, KO8/CA71429] Funding Source: Medline NHLBI NIH HHS [HL60788, R01/HL63008] Funding Source: Medline NIGMS NIH HHS [GM53249] Funding Source: Medline 

主　　题：结合部位 钙结合蛋白质类 细胞 培养的 细胞因子类/药理学 DNA结合蛋白质类 炎症/代谢 炎症介导素类/代谢 炎症介导素类/生理学 膜糖蛋白类/代谢 突变 NF-κB/代谢 NF-κB/生理学 神经组织蛋白质类/代谢 一氧化氮合酶/代谢 一氧化氮合酶Ⅱ型 蛋白质结构 三级 原癌基因蛋白质类 突触结合蛋白质Ⅰ 突触结合蛋白质类 反式激活因子类/遗传学 反式激活因子类/代谢 反式激活因子类/生理学 转录因子 血管疾病/代谢 人类 

摘      要：Inflammation is a hallmark of several vascular diseases. The nuclear factor kappaB (NF-kappaB) transcription factors are dimeric proteins involved in the activation of a large number of genes in response to inflammatory stimuli. We report the involvement of a novel member of the ETS transcription factor, ESE-1, in mediating vascular inflammation. ESE-1 is induced in response to inflammatory cytokines and lipopolysaccharide in vascular smooth muscle cells, endothelial cells, and cells of the monocyte-macrophage lineage. This induction occurs within hours of stimulation and is mediated by NF-kappaB transactivation of the ESE-1 promoter. We have identified the inducible form of nitric-oxide synthase (NOS2) as a putative target for ESE-1, ESE-1 can bind to the p50 subunit of NF-kappaB, and cotransfection of ESE-1 with the p50 and p65 subunits of NF-kappaB synergistically enhances transactivation of the NOS2 promoter by ESE-1, An ESE-1-binding site within the NOS2 promoter has been identified, the site-directed mutagenesis of which completely abolishes the ability of ESE-1 to transactivate the NOS2 promoter. Finally, in a mouse model of endotoxemia, associated with acute vascular inflammation, ESE-1 is strongly expressed in vascular endothelium and smooth muscle cells. In summary, ESE-1 represents a novel mediator of vascular inflammation.