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尼罗罗非鱼脂酶的分子特征和免疫功能:在肿瘤坏死因子-α分泌调控中的作用。

Molecular characterization and immune functions of lipasin in Nile tilapia (Oreochromis niloticus): Involvement in the regulation of tumor necrosis factor-α secretion.

机构信息

Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, PR China.

Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, PR China.

出版信息

Fish Shellfish Immunol. 2023 Feb;133:108549. doi: 10.1016/j.fsi.2023.108549. Epub 2023 Jan 14.

Abstract

Lipasin, the product of the angiopoietin-like 8 (angptl8) gene, is known as a critical regulator of plasma lipid metabolism. However, its immune function in vertebrates is currently poorly understood. By 5'/3'-rapid amplification of cDNA ends (RACE), we established the structural identity of Nile tilapia (Oreochromis niloticus) angptl8. The transcripts of tilapia angptl8 were widely expressed in various tissues, with the highest levels in the liver. Following lipopolysaccharide in vivo challenges, time-dependent angptl8 gene expression was observed in the head kidney and liver. On the basis of the sequence obtained, we produced recombinant lipasin that inhibited lipoprotein lipase activity. Treatment of head kidney leukocytes with lipasin stimulated tumor necrosis factor-α (TNF-α) secretion and gene expression. In addition, lipasin-induced TNF-α secretion could be prevented by inhibiting the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, lipasin enhanced the phosphorylation and degradation of IκBα and promoted translocation of the p65 subunit of NF-κB to the nucleus. Collectively, the current findings suggested that lipasin was involved in the immune response of Nile tilapia and stimulated TNF-α secretion by activating the NF-κB pathway in tilapia head kidney leukocytes.

摘要

脂质运载蛋白 8(Lipasin),又称为血管生成素样蛋白 8(angiopoietin-like 8,angptl8)的产物,是一种重要的血浆脂质代谢调控因子。然而,其在脊椎动物中的免疫功能目前还知之甚少。通过 5'/3'-快速扩增 cDNA 末端(RACE),我们确定了尼罗罗非鱼(Oreochromis niloticus)angptl8 的结构特征。尼罗罗非鱼 angptl8 的转录本在各种组织中广泛表达,其中肝脏中的表达水平最高。在体内受到脂多糖刺激后,头肾和肝脏中 angptl8 基因的表达呈现时间依赖性。基于获得的序列,我们生产了重组脂质运载蛋白,该蛋白可抑制脂蛋白脂肪酶的活性。脂质运载蛋白处理头肾白细胞可刺激肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)的分泌和基因表达。此外,通过抑制核因子-κB(Nuclear factor-kappa B,NF-κB)信号通路,可阻止脂质运载蛋白诱导的 TNF-α 分泌。此外,脂质运载蛋白可增强 IκBα 的磷酸化和降解,并促进 NF-κB 的 p65 亚基向核内易位。综上所述,这些发现表明,脂质运载蛋白参与了尼罗罗非鱼的免疫反应,并通过激活尼罗罗非鱼头肾白细胞中的 NF-κB 通路刺激 TNF-α 的分泌。

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