Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China.
Fish Shellfish Immunol. 2020 Dec;107(Pt A):156-162. doi: 10.1016/j.fsi.2020.09.009. Epub 2020 Sep 19.
NF-κB is a typical transcription factor that regulates expression of various genes involved in inflammatory and immune responses. Therefore, it is essential that NF-κB signaling tightly regulated to maintain immune balance. Compared with those of mammals, the regulatory mechanisms of NF-κB signaling is rarely reported in teleost fish. IκBα is a prominent negative feedback regulator in the NF-κB signaling system. In this study, we determined that IRF11 enhances the inhibitory effect of IκBα on NF-κB activation in teleost fish. Overexpression of IRF11 can inhibit IκBα degradation, whereas its knockdown has the opposite effect of IκBα. Our study further indicates that IκBα was regulated via ubiquitin-proteasome degradation pathway, IRF11 inhibits IκBα in ubiquitin-proteasome degradation. This study provides a novel evidence on the regulation of innate immune signaling pathways in teleost fish and thus provides new insights into the regulatory mechanisms in mammals.
NF-κB 是一种典型的转录因子，可调节参与炎症和免疫反应的各种基因的表达。因此，NF-κB 信号的严格调控对于维持免疫平衡至关重要。与哺乳动物相比，鱼类中 NF-κB 信号的调控机制很少有报道。IκBα 是 NF-κB 信号系统中重要的负反馈调节因子。在本研究中，我们发现 IRF11 增强了 IκBα 对鱼类 NF-κB 激活的抑制作用。IRF11 的过表达可以抑制 IκBα 的降解，而其敲低则具有相反的 IκBα 作用。我们的研究进一步表明，IκBα 是通过泛素蛋白酶体降解途径进行调控的，IRF11 抑制了 IκBα 的泛素蛋白酶体降解。本研究为鱼类先天免疫信号通路的调控提供了新的证据，也为哺乳动物的调控机制提供了新的见解。
