Biology Department, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Curr Top Microbiol Immunol. 2011;349:245-63. doi: 10.1007/82_2010_105.
As described extensively in this issue, NF-κB transcription factors regulate a number of important physiological processes, including inflammation and immune responses, cell growth and survival, and the expression of certain viral genes. Moreover, NF-κB activity is elevated in and contributes to the pathology of several human diseases, including many cancers and chronic inflammatory diseases. Therefore, there has been great interest in the characterization and development of methods to limit NF-κB signaling for pharmacological intervention. This article describes some of the approaches that have been employed to inhibit NF-κB using in vitro and in vivo experimental models. Moreover, some examples of the clinical use of NF-κB inhibitors are discussed, primarily for the treatment of two B-cell malignancies, multiple myeloma and diffuse large B-cell lymphoma. Finally, the rationale and strategies for inhibiting specific NF-κB subunit activity for disease therapy are discussed.
如本期所广泛描述的，NF-κB 转录因子调节许多重要的生理过程，包括炎症和免疫反应、细胞生长和存活以及某些病毒基因的表达。此外，NF-κB 的活性在几种人类疾病的发病机制中升高，并对此作出贡献，这些疾病包括许多癌症和慢性炎症性疾病。因此，人们对 NF-κB 信号通路的特征描述和抑制方法的开发非常感兴趣，以便进行药理学干预。本文描述了一些在体外和体内实验模型中用于抑制 NF-κB 的方法。此外，还讨论了 NF-κB 抑制剂的一些临床应用实例，主要用于治疗两种 B 细胞恶性肿瘤，即多发性骨髓瘤和弥漫性大 B 细胞淋巴瘤。最后，讨论了抑制特定 NF-κB 亚基活性用于疾病治疗的基本原理和策略。
