Expression and Function Analysis of Interleukin-17A/F1, 2, and 3 Genes in Yellow Catfish (Pelteobagrus fulvidraco): Distinct Bioactivity of Recombinant IL-17A/F1, 2, and 3.

Expression and Function Analysis of Interleukin-17A/F1, 2, and 3 Genes in Yellow Catfish (Pelteobagrus fulvidraco): Distinct Bioactivity of Recombinant IL-17A/F1, 2, and 3.
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黄颡鱼 (Pelteobagrus fulvidraco) 中 IL-17A/F1、2 和 3 基因的表达和功能分析:重组 IL-17A/F1、2 和 3 的独特生物活性

DOI:
10.3389/fimmu.2021.626895
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发表时间:
2021
影响因子:
7.3
通讯作者:
Wei KJ
Wei KJ
中科院分区:
医学2区
文献类型:
--
作者:
Zhou X;Zhang GR;Ji W;Shi ZC;Ma XF;Luo ZL;Wei KJ

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在哺乳动物中,白细胞介素-17细胞因子家族在急性和慢性炎症反应中起关键作用。在鱼类中,已经鉴定出三种白细胞介素-17 A/F(IL-17 A/F)基因与哺乳动物IL-17 A和IL-17 F同源,但对其功能活性知之甚少。本研究从黄颡鱼(Pelteobagrus fulvidraco)中克隆了Pf_IL-17 A/F1、2和3基因,它们在蛋白质结构和外显子长度上存在差异,可能具有不同的生物活性。实时荧光定量PCR分析表明,Pf_IL-17 A/F基因在健康成鱼的血液和粘膜组织(皮肤+粘液和鳃)中均有高表达。结果表明,黄颡鱼IL-17 A/F1、2和3基因在鳃、皮肤+粘液、头肾和脾脏中的表达量在爱德华氏菌(Edwardsiella ictaluri)刺激后显著上调,在植物血凝素(PHA)、脂多糖(LPS)、肽聚糖(PGN)和聚肌胞苷酸(Poly I:C)刺激后显著上调。提示Pf_IL-17 A/F1、2和3基因可能在机体免疫调节中起重要作用。此外,重组(r)Pf_IL-17 A/F1、2和3蛋白可显著诱导促炎细胞因子、趋化因子和抗菌肽基因的mRNA表达,且rPf_IL-17 A/F2和3蛋白比rPf_IL-17 A/F1蛋白更强地促进PBLs的吞噬功能。rPf_IL-17 A/F1、2和3蛋白可能通过IL-17 RA、ACT 1、TRAF 6、TRAF 2、TRAF 5和TAK 1激活NF-κB和MAPK信号通路,提示3种Pf_IL-17 A/F蛋白在促进炎症反应中可能发挥不同的作用。
In mammals, Interleukin-17 cytokine family plays critical roles in both acute and chronic inflammatory responses. In fish species, three Interleukin-17A/F (IL-17A/F) genes have been identified to be homologous to mammalian IL-17A and IL-17F, but little is known about their functional activity. In this study, Pf_IL-17A/F1, 2 and 3 genes were cloned from yellow catfish (Pelteobagrus fulvidraco) and they differed in protein structure and exon length, implying that they may have divergent bioactivity. Real-time quantitative PCR analyses revealed that three Pf_IL-17A/F genes were highly expressed in blood and mucosal tissues (skin+mucus and gill) from healthy adult fish. The mRNA expressions of Pf_IL-17A/F1, 2 and 3 genes were significantly up-regulated in the gill, skin+mucus, head kidney and spleen after challenge with Edwardsiella ictaluri and in the isolated peripheral blood leucocytes (PBLs) of yellow catfish after stimulation with phytohaemagglutinin (PHA), lipopolysaccharides (LPS), peptidoglycan (PGN) and polyinosinic-polycytidylic acid (Poly I:C). These results indicate that Pf_IL-17A/F1, 2 and 3 genes may play a vital role in the regulation of immune against pathogens. Additionally, the recombinant (r) Pf_IL-17A/F1, 2 and 3 proteins significantly induced the mRNA expressions of proinflammatory cytokines, chemokines and antibacterial peptides genes, and the rPf_IL-17A/F 2 and 3 proteins promoted phagocytosis of PBLs more powerfully than the rPf_IL-17A/F1. Furthermore, the rPf_IL-17A/F1, 2 and 3 proteins might activate the NF-κB and MAPK signal pathways by IL-17RA, ACT1, TRAF6, TRAF2, TRAF5 and TAK1, indicating that the three Pf_IL-17A/F proteins may play different roles in promoting inflammatory response.
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