Key Laboratory of Fishery Drug Development of Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology of Guangdong Province, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.
Key Laboratory of Fishery Drug Development of Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology of Guangdong Province, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China; College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Fish Shellfish Immunol. 2020 May;100:309-316. doi: 10.1016/j.fsi.2020.03.022. Epub 2020 Mar 12.
As a central pro-inflammatory cytokine, interleukin-1β (IL-1β) plays critical roles in the inflammatory response, pathogen infection, and immunological challenges in mammals. Although fish IL-1β has been confirmed to participate in inflammatory response to pathogen infection, few studies have been performed to characterize the antibacterial and bactericidal functions of fish IL-1β. In this study, snakehead (Channa argus) IL-1β (shIL-1β) and its receptors, shIL-1R1 and shIL-1R2, were cloned and functionally characterized. ShIL-1β contained the IL-1 family signature domain, and a potential cutting site at Asp that presented in all vertebrate IL-1β sequences. ShIL-1R1 had three extracellular IG-like domains and one intracellular signal TIR domain, while shIL-1R2 had three extracellular IG-like domain but lacked the intracellular signal TIR domain. ShIL-1β, shIL-1R1, and shIL-1R2 were constitutively expressed in all tested tissues, and their expressions could be induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo, and by LTA, LPS, and Poly (I:C) in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shIL-1β upregulated the expression of endogenous shIL-1β, shIL-R1, and shIL-R2 in snakehead HKLs, and enhanced intracellular bactericidal activity. Taken together, this study found that, like IL-1β and its receptors in mammals, shIL-1β and its receptors play crucial roles in antibacterial innate immunity. This provides new insight into the evolution of IL-1β function in vertebrates.
作为一种重要的促炎细胞因子,白细胞介素-1β(IL-1β)在哺乳动物的炎症反应、病原体感染和免疫挑战中发挥着关键作用。尽管鱼类的 IL-1β已被证实参与了对病原体感染的炎症反应,但对其抗菌和杀菌功能的研究还很少。本研究克隆并功能表征了乌鳢(Channa argus)IL-1β(shIL-1β)及其受体 shIL-1R1 和 shIL-1R2。shIL-1β 含有 IL-1 家族特征结构域,以及在所有脊椎动物 IL-1β 序列中存在的潜在切割位点 Asp。shIL-1R1 具有三个细胞外 IG 样结构域和一个细胞内信号 TIR 结构域,而 shIL-1R2 具有三个细胞外 IG 样结构域,但缺乏细胞内信号 TIR 结构域。shIL-1β、shIL-1R1 和 shIL-1R2 在所有检测的组织中均呈组成性表达,并且它们的表达可以被体内的嗜水气单胞菌和诺卡氏菌以及体外的 LTA、LPS 和 Poly(I:C)诱导。此外,重组 shIL-1β 上调了乌鳢头肾白细胞(HKL)中内源性 shIL-1β、shIL-R1 和 shIL-R2 的表达,并增强了细胞内杀菌活性。总之,本研究发现,与哺乳动物的 IL-1β 及其受体一样,shIL-1β 及其受体在抗菌固有免疫中发挥着关键作用。这为 IL-1β 在脊椎动物中的功能进化提供了新的见解。