TBK1在炎症性疾病发生机制中的作用

Effect of TBK1 in pathogenesis of inflammatory diseases

TANK结合激酶1(TBK1)作为非经典IκB激酶(IKK),在核转录因子(NF-κB)信号通路中发挥着重大作用,且不同于经典IKK,TBK1能够磷酸化干扰素调节因子3(IRF3)和干扰素调节因子7(IRF7),调节Ⅰ型干扰素产生,由此在维持免疫系统的稳态中发挥重大作用。凭借在炎症信号通路中的多种作用,TBK1与多种炎症性疾病的发病机制有关,例如类风湿关节炎(RA)、系统性红斑狼疮(SLE)、革兰阴性细菌败血症,以TBK1为靶点治疗这类炎症性疾病,为该类疾病的治疗提供了新的治疗思路。本文通过对TBK1结构功能及其活化进行综述,并探讨其在炎症性疾病发病机制中的作用。

TBK1,as a non-classical IKK kinase,plays an important role in the nuclear factor-B(NF-B)signaling pathway.Unlike classical IKK kinase,TBK1 can phosphorylate IFN regulatory factors(IRF)3 and 7 to regulate the production of type I interferon.TBK1 plays an important role in maintaining the homeostasis of the immune system.By virtue of its multiple roles in the inflammatory signaling pathways,TBK1 is associated with the pathogenesis of a variety of inflammatory diseases,such as rheumatoid arthritis(RA),systemic lupus erythematosus(SLE),Gram-negative bacterial sepsis,TBK1 as a target spot for treating this kind of inflammatory disease offers a new therapeutic idea for the treatment of these inflammatory diseases.This paper reviews the structure,function and activation of TBK1,and investigates its role in the pathogenesis of inflammatory diseases.