Two Types of TNF-α Exist in Teleost Fish: Phylogeny, Expression, and Bioactivity Analysis of Type-II TNF-α3 in Rainbow Trout Oncorhynchus mykiss
Two Types of TNF-α Exist in Teleost Fish: Phylogeny, Expression, and Bioactivity Analysis of Type-II TNF-α3 in Rainbow Trout Oncorhynchus mykiss
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DOI：
10.4049/jimmunol.1301584
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发表时间：
2013-12-15
影响因子：
4.4
通讯作者：
Wang, Tiehui
中科院分区：
文献类型：
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作者：
Hong, Suhee;Li, Ronggai;Wang, Tiehui
TNF-α是参与全身炎症和免疫细胞调节的细胞因子。它主要由活化的巨噬细胞作为膜或分泌形式产生。在虹鳟鱼中，之前描述了两种TNF-α分子。在这篇文章中，我们报告了第三个TNF-α（TNF-α 3），只有低身份的已知鳟鱼分子。鳟鱼和其他鱼类的系统发育树和同线性分析表明，两种类型（命名为I和II）的TNF-α存在于硬骨鱼。鱼类II型TNF-α具有短柄，可能影响其酶促释放或将其限制为膜结合形式。在组织和细胞系中，鳟鱼TNF-α 3的组成型表达通常低于其他两种基因，但巨噬细胞RTS-11细胞系除外，其中表达较高。所有三种TNF-α亚型的表达可以通过细胞系和原代巨噬细胞中的粗LPS、肽聚糖、聚肌苷酸：聚胞苷酸和rIFN-γ以及细菌和病毒感染来调节。TNF-α 3在LPS刺激后的早期时间点是最具响应性的基因，并且可以被T细胞刺激剂PHA高度诱导，这表明它是特别重要的TNF-α同种型。CHO细胞产生的rTNF-α 3在不同的细胞系和原代巨噬细胞中具有生物活性。在后者中，它诱导促炎细胞因子（IL-1 β、IL-6、IL-8、IL-17 C和TNF-α）、负调节因子（SOCS 1 -3、TGF-β 1b）、抗微生物肽（cathelicidin-1和hepcidin）和巨噬细胞生长因子IL-34的表达，验证了其在鱼类的炎性细胞因子网络和巨噬细胞生物学中的关键作用。
TNF-alpha is a cytokine involved in systemic inflammation and regulation of immune cells. It is produced chiefly by activated macrophages as a membrane or secreted form. In rainbow trout, two TNF-alpha molecules were described previously. In this article, we report a third TNF-alpha (TNF-alpha 3) that has only low identities to known trout molecules. Phylogenetic tree and synteny analyses of trout and other fish species suggest that two types (named I and II) of TNF-alpha exist in teleost fish. The fish type-II TNF-alpha has a short stalk that may impact on its enzymatic release or restrict it to a membrane-bound form. The constitutive expression of trout TNF-alpha 3 was generally lower than the other two genes in tissues and cell lines, with the exception of the macrophage RTS-11 cell line, in which expression was higher. Expression of all three TNF-alpha isoforms could be modulated by crude LPS, peptidoglycan, polyinosinic: polycytidylic acid, and rIFN-gamma in cell lines and primary macrophages, as well as by bacterial and viral infections. TNF-alpha 3 is the most responsive gene at early time points post-LPS stimulation and can be highly induced by the T cell-stimulant PHA, suggesting it is a particularly important TNF-alpha isoform. rTNF-alpha 3 produced in CHO cells was bioactive in different cell lines and primary macrophages. In the latter, it induced the expression of proinflammatory cytokines (IL-1 beta, IL-6, IL-8, IL-17C, and TNF-alpha s), negative regulators (SOCS1-3, TGF-beta 1b), antimicrobial peptides (cathelicidin-1 and hepcidin), and the macrophage growth factor IL-34, verifying its key role in the inflammatory cytokine network and macrophage biology of fish.