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MicroRNA-29b 通过抑制橙色斑点石斑鱼(Epinephelus coioides)IFNγ 的产生来调节先天免疫反应。

MicroRNA-29b modulates the innate immune response by suppressing IFNγs production in orange-spotted grouper (Epinephelus coioides).

机构信息

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory for Aquatic Economic Animals and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, 510275, Guangzhou, PR China.

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory for Aquatic Economic Animals and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, 510275, Guangzhou, PR China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University, Guangzhou, 510275, PR China.

出版信息

Fish Shellfish Immunol. 2020 Sep;104:537-544. doi: 10.1016/j.fsi.2020.05.057. Epub 2020 May 27.

DOI:10.1016/j.fsi.2020.05.057
PMID:32470508
Abstract

Interferon-γ (IFNγ), a type II interferon, is essential to host resistance against various infections. Unlike other vertebrates, fish have two types of IFNγs, IFNγ1 (also named IFNγ-rel) and IFNγ2. MicroRNAs (miRNAs) regulate multiple biological processes by suppressing mRNA translation or inducing mRNA degradation. Among them, miR-29 can directly target IFNγ and affact innate and adaptive immune responses in mice. There are five members of the miR-29 family in orange-spotted grouper (Epinephelus coioides), which share the same miRNA seed region. However, whether miR-29 directly targets E. coioides IFNγs and regulate IFNγ production is still unknown. In the present study, the negative correlation between miR-29b and both IFNγs in immune tissues of healthy E. coioides and grouper spleen cells (GS cells) stimulated with LPS or poly I:C was demonstrated. Moreover, dual-luciferase reporter assays and western blotting were performed to demonstrate that miR-29b suppressed E. coioides IFNγ production. Studies of NO production in GS cells after miR-29b transfection revealed that miR-29b overexpression affected NO production through the downregulation of IFNγ expression. Taken together, our results suggest that miR-29b may directly target E. coioides IFNγs and modulate IFNγ-mediated innate immune responses by suppressing E. coioides IFNγs production.

摘要

干扰素-γ(IFNγ)是一种 II 型干扰素,对宿主抵抗各种感染至关重要。与其他脊椎动物不同,鱼类有两种类型的 IFNγ,IFNγ1(也称为 IFNγ-rel)和 IFNγ2。微小 RNA(miRNA)通过抑制 mRNA 翻译或诱导 mRNA 降解来调节多种生物过程。其中,miR-29 可以直接靶向 IFNγ,并影响小鼠的先天和适应性免疫反应。在橙色斑点石斑鱼(Epinephelus coioides)中有五个 miR-29 家族成员,它们具有相同的 miRNA 种子区域。然而,miR-29 是否直接靶向 E. coioides IFNγs 并调节 IFNγ 的产生仍不清楚。在本研究中,证明了健康 E. coioides 免疫组织和用 LPS 或聚 I:C 刺激的石斑鱼脾细胞(GS 细胞)中 miR-29b 与两种 IFNγ 之间的负相关。此外,进行了双荧光素酶报告基因检测和 Western blot 实验,证明 miR-29b 抑制 E. coioides IFNγ 的产生。miR-29b 转染后 GS 细胞中 NO 产生的研究表明,miR-29b 通过下调 IFNγ 的表达影响 NO 的产生。综上所述,我们的研究结果表明,miR-29b 可能通过直接靶向 E. coioides IFNγs 并抑制 E. coioides IFNγs 的产生来调节 IFNγ 介导的先天免疫反应。

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