p20, Molecular Shortstop for Inflammatory Lung Diseases

描述(申请人摘要)：转录因子CAAT增强子 结合蛋白β(C/EBPbeta)是协调炎症反应的关键因素。 回应。具体地说，编码促炎基因的表达 细胞因子IL-6和IL-8受C/EBPβ调节。C/EBP测试版可以是 根据主要的异构体而定的炎症激活剂或抑制剂 制作。我们的数据表明，培养中的呼吸道上皮细胞终止 IL-6和IL-8的产生促进抑制性C/EBPβ的产生 异构体(P20)和具有夸大炎症反应细胞 这种异构体的产生量减少。此外，当动物被给予 内毒素肺组织产生的抑制性C/EBPβ减少 异构体和激活剂异构体产量的增加。由于IL-6 产生量与人类脓毒症的严重程度和干预措施相关 在这种情况下，减少IL-6会改善预后，我们认为增加 肺中抑制性C/EBPβ亚型可能对 脓毒症的肺部并发症。

DESCRIPTION (Applicant's abstract): The transcription factor CAAT enhancer binding protein beta (C/EBPbeta) is a key factor orchestrating the inflammatory response. Specifically, expression of the genes encoding the pro-inflammatory cytokines IL-6 and on IL-8 are regulated by C/EBPbeta. C/EBPbeta can be either an activator or an inhibitor of inflammation depending on the dominant isoforms produced. Our data indicate that airway epithelial cells in culture terminate production of IL-6 and IL-8 increasing production of inhibitory C/EBPbeta isoform (p20) and that cells that have an exaggerated inflammatory response produce decreased amounts of this isoform. In addition, when animals are given endotoxin there is a decrease in lung production of the inhibitory C/EBPbeta isoform and an increase in production of the activator isoform. Since IL-6 production correlates with severity of sepsis in humans and interventions that decrease IL-6 improve outcome in that setting, we believe that increasing the inhibitory C/EBPbeta isoform in the lungs could be therapeutic for the pulmonary complications of sepsis.