Blackwell T S, Christman J W
Department of Veterans Affairs, Nashville, Tennessee, USA.
Am J Respir Cell Mol Biol. 1997 Jul;17(1):3-9. doi: 10.1165/ajrcmb.17.1.f132.
Transcription factors are DNA-binding proteins that regulate gene expression. Nuclear factor-kappa B (NF-kappa B) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases, such as adult respiratory distress syndrome (ARDS) and sepsis syndrome. Activation and regulation of NF-kappa B are tightly controlled by a group of inhibitory proteins (I kappa B) that sequester NF-kappa B in the cytoplasm of immune/inflammatory effector cells. NF-kappa B activation involves signaled phosphorylation, ubiquitination, and proteolysis of I kappa B. Liberated NF-kappa B migrates to the nucleus, where it binds to specific promoter sites and activates gene transcription. The activation of NF-kappa B initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-kappa B activation. Recently, activation of NF-kappa B has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models. Activation of NF-kappa B can be inhibited in vivo by treatment with antioxidants, corticosteroids, and the induction of endotoxin tolerance. Identification of more specific and efficacious inhibitors of NF-kappa B activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases.
转录因子是一类调控基因表达的DNA结合蛋白。核因子-κB（NF-κB）是许多细胞因子最大程度表达的关键转录因子，这些细胞因子参与诸如成人呼吸窘迫综合征（ARDS）和脓毒症综合征等炎症性疾病的发病机制。NF-κB的激活和调控受到一组抑制蛋白（IκB）的严格控制，这些抑制蛋白将NF-κB隔离在免疫/炎症效应细胞的细胞质中。NF-κB的激活涉及IκB的信号磷酸化、泛素化和蛋白水解。释放出来的NF-κB迁移至细胞核，在那里它与特定的启动子位点结合并激活基因转录。NF-κB的激活引发细胞外和细胞内的调节事件，通过调节NF-κB的激活导致炎症级联反应的自动调节。最近，NF-κB的激活与ARDS相关联，并且在动物模型中已被证明是嗜中性粒细胞炎症起始的关键近端步骤。在体内，通过使用抗氧化剂、皮质类固醇进行治疗以及诱导内毒素耐受，可以抑制NF-κB的激活。鉴定更具特异性和有效性的NF-κB激活抑制剂可能对治疗细胞因子介导的炎症性疾病有益。
