大西洋鲑PKC-δ磷酸化修饰调控ILs表达的机制

蛋白激酶C-δ（PKC-δ）是一种在先天性免疫及炎症反应中发挥重要功能的丝氨酸/苏氨酸蛋白激酶。已有研究表明PKC-δ可介导TLR4/MyD88/NF-κB信号通路调控ILs的表达。在大西洋鲑中，PKC-δ调控ILs的表达机制尚无研究报道。我们在前期工作中发现在大西洋鲑感染杀鲑气单胞菌的肾脏组织中，PKC-δ发生磷酸化修饰并显著上调表达。本实验拟通过RNAi、过表达、定点突变、蛋白杂交、免疫共沉淀等技术，解析Ss-PKC-δ磷酸化修饰对ILs表达的调控作用，阐述Ss-PKC-δ磷酸化修饰激活TLR4/MyD88/NF-κB信号通路调控ILs表达的分子机制。研究成果将极大地丰富大西洋鲑先天免疫的理论知识，并为防治杀鲑气单胞菌感染大西洋鲑提供新思路。

PKC-δ is an important serine/threonine protein kinase which plays a crucial role in innate immunology and inflammatory. Previous research had indicated PKC-δ could regulate expression of inflammatory cytokines by signal pathway of TLR4/MyD88/NF-κB. Almost no reports about the immunologic mechanism of PKC-δ in Salmon salar in regulating inflammatory cytokines till now. Based on our previous research, we selecte the phosphorylation of Salmo salar Protein kinase C-δ (Ss-PKC-δ) with higher expression in kidneys of A. salmonicida-infected fish. The RNA interference, mRNA over-expression assays, site-directed mutagenesis, western blot and co-immunoprecipitation are used to analyze the regulatory mechanism of ILs by Ss-PKC-δ phosphorylation, and clarify related inflammatory signaling pathway activation after Ss-PKC-δ phosphorylation and the immunologic mechanism regulated by the signaling pathway of TLR4/MyD88/NF-κB. These studies will promote the understanding of the immune modulatory mechanism of Salmo salar against A. salmonicida, also enrich the theory of immunity in Salmo salar and are helpful to develop new strategies for disease control of A. salmonicida in Salmo salar.