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大黄鱼巨噬细胞移动抑制因子(MIF)参与抗菌免疫反应。

Macrophage migration inhibitory factor (MIF) of golden pompano (Trachinotus ovatus) is involved in the antibacterial immune response.

机构信息

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, PR China; Hainan Provincial Key Laboratory for Tropical Hydrobiology and Biotechnology, College of Marine Science, Hainan University, PR China.

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, PR China.

出版信息

Dev Comp Immunol. 2022 Aug;133:104445. doi: 10.1016/j.dci.2022.104445. Epub 2022 May 17.

DOI:10.1016/j.dci.2022.104445
PMID:35588935
Abstract

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with a unique structure involved in immune regulation and inflammation. In the present study, we identified a MIF from Trachinotus ovatus (golden pompano) and analyzed its function. TroMIF shares high homology (58.26%-94.78%) with the other known MIF sequences of vertebrates. TroMIF is most closely related to large yellow croaker (Larimichthys crocea). The expression of TroMIF was most abundant in the liver and head kidney, and was significantly up-regulated after Edwardsiella tarda infection. The subcellular localization of TroMIF was mostly distributed in the cytoplasm. In vitro results revealed that the recombinant protein rTroMIF could inhibit the migration of head kidney lymphocytes (HKLs) and macrophages (HKMs) and enhance the phagocytic activity of HKMs. As a pro-inflammatory cytokine, rTroMIF could increase the expression levels of some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), IL-6, IL-8, and interferon-gamma (IFN-γ) and decrease the expression of IL-10. The rTroMIF was proved to have enzymatic redox activity in vitro. Furthermore, overexpression of TroMIF in the head kidney cell line of golden pompano could significantly enhance its ability to resist E. tarda infection from 1 h to 4 h. The knockdown of TroMIF expression induced a significant increase in the number of bacteria after E. tarda infection at 1, 2, and 4 hpi. Our results suggest that TroMIF is an essential effector of the innate immune system and plays a pivotal role in antibacterial immunity.

摘要

巨噬细胞移动抑制因子(MIF)是一种具有独特结构的多功能细胞因子,参与免疫调节和炎症反应。本研究从卵形鲳鲹(金鲳鱼)中鉴定了一种 MIF,并分析了其功能。TroMIF 与其他已知脊椎动物的 MIF 序列具有高度同源性(58.26%-94.78%)。TroMIF 与大黄鱼(Larimichthys crocea)最为密切相关。TroMIF 的表达丰度在肝脏和头肾中最高,在爱德华氏菌感染后显著上调。TroMIF 的亚细胞定位主要分布在细胞质中。体外实验结果表明,重组蛋白 rTroMIF 可抑制头肾淋巴细胞(HKLs)和巨噬细胞(HKMs)的迁移,并增强 HKMs 的吞噬活性。作为一种促炎细胞因子,rTroMIF 可增加一些促炎细胞因子的表达水平,包括肿瘤坏死因子-α(TNF-α)、白细胞介素 1-β(IL-1β)、IL-6、IL-8 和干扰素-γ(IFN-γ),并降低白细胞介素 10(IL-10)的表达水平。rTroMIF 被证明具有体外酶促氧化还原活性。此外,在卵形鲳鲹头肾细胞系中过表达 TroMIF 可显著增强其在 1 至 4 小时抵抗爱德华氏菌感染的能力。在 1、2 和 4 hpi 时 TroMIF 表达下调后,感染爱德华氏菌后的细菌数量显著增加。我们的结果表明,TroMIF 是先天免疫系统的重要效应因子,在抗菌免疫中发挥关键作用。

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