Studies on the structure and function of tumor necrosis factor (TNF) in fish

鱼类肿瘤坏死因子（TNF）的结构与功能研究

• 批准号: 15380136
• 负责人: NAKANISHI Teruyuki
• 金额: $ 9.47万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15380136/
• 关键词: Rainbow trout; Zebrafish; Ayu fish; Banded dogfish; TNF alpha; Transgenic; mRNA expression; Recombinant TNF; GFP; 組換えTNF; TNFレセプターデコイ; LPS; 定量PCR法; 組換えニジマスTNF; CCケモカイン

Tumor necrosis factor (TNF) is a primary mediator of immune regulation and the inflammatory response. TNF is also known to be a mediator involved in the interaction between endocrine nervous and immune systems. There have been also reported that TNF/LT family cytokines play important role in development, maturation and maintenance of secondary lymphoid organs. Thus TNF is one of the most important cytokines investigated so far from various fields and aspects.To understand the broad range of biological activities of TNF we tried to investigate its pleiotropic nature from phylogenetical and ontogenetical points of view. In the present research we obtained the following results :1.Structure and function of fish TNFWe isolated one TNF homologue from Ayu fish and two types of TNF from rainbow trout and zebrafish. We also cloned TNF decoy receptor 3 (DcR3) together with several cytokines from cartilaginous fish. Structure and expression of these fish TNF and TNF super family genes resembles to those of mammalian TNF.2.Production of recombinant TNF and its biological activityPurified recombinant TNF of Ayu fish induced the production of superoxide from head-kidney leukocytes.3.Expression of TNF mRNA after stimulation with LPS and/or bacteriaExpression of TNF in tissues after stimulation with LPS was different between two types of TNF in rainbow trout. Studies using transgenic rainbow trout introduced with TNF promoter linked to green fluorescence protein (GFP) as a reporter gene showed that TNF secreting cells are involved in envelopment response against bacteria.4.Role of TNF in developmentTwo types of TNF were weakly expressed at the nervous system of zebrafish embryos, and increased TNF expression toward hatching was observed in Ayu embryos suggesting the role of TNF in the morphogenesis of embryonic organs.

肿瘤坏死因子（TNF）是免疫调节和炎症反应的主要介质。TNF也被认为是参与内分泌、神经和免疫系统相互作用的中介。也有报道称TNF/LT家族细胞因子在次要淋巴器官的发育、成熟和维持中发挥重要作用。因此，TNF是迄今为止从各个领域和方面研究的最重要的细胞因子之一。为了了解TNF广泛的生物活性，我们试图从系统发育和个体发生的角度研究其多效性。在本研究中，我们得到了以下结果：1。鱼类TNF的结构与功能我们从阿玉鱼中分离到1种TNF同源物，从虹鳟和斑马鱼中分离到2种TNF。我们还从软骨鱼类中克隆了TNF诱饵受体3 （DcR3）和几种细胞因子。这些鱼类TNF和TNF超家族基因的结构和表达与哺乳动物TNF相似。重组TNF的产生及其生物活性纯化的重组TNF可诱导头肾白细胞产生超氧化物。LPS和/或细菌刺激后TNF mRNA的表达两种类型的TNF在虹鳟鱼中刺激后组织中表达不同。引入与绿色荧光蛋白（GFP）相关的TNF启动子作为报告基因的转基因虹鳟鱼的研究表明，TNF分泌细胞参与了对细菌的包膜反应。两种类型的TNF在斑马鱼胚胎的神经系统中表达较弱，而在Ayu胚胎中，TNF在孵化过程中表达增加，提示TNF在胚胎器官形态发生中的作用。

项目成果

Molecular cloning and preliminary expression analysis of banded dogfish (Triakis scyllia) CC chemokine cDNAs by use of suppression subtractive hybridization.

利用抑制消减杂交对带状角鲨 (Triakis scyllia) CC 趋化因子 cDNA 进行分子克隆和初步表达分析。

• 发表时间: 2005
• 期刊: Immunogenetics 56
• 作者: T.Gao;Y.Wng;J.Liu;S.Watanabe;R.Fuseya;伏屋 玲子;Natsuko Kajiwara et al.;Natsuko Kajiwara et al.;Karri Ramu et al.;Inoue Yuuki
• 通讯作者: Inoue Yuuki

Efficient intracellular delivery of rifampicin to alveolar macrophages using rifampicin-loaded PLGA microspheres: effects of molecular weight and composition of PLGA on release of rifampicin

• DOI: 10.1016/j.colsurfb.2004.03.018
• 发表时间: 2004-07-01
• 期刊: COLLOIDS AND SURFACES B-BIOINTERFACES
• 影响因子: 5.8
• 作者: Makino, K;Nakajima, T;Terada, H
• 通讯作者: Terada, H

Yoshimura, H., Dhar, DK., Nakamoto, T., Kotoh, T., Takano, M., Soma, G-I, Nagasue, N: "Prognostic significance of tumor necrosis factor receptor in colorectal adenocarcinoma"Anticancer Research. 23. 85-89 (2003)

Yoshimura, H.、Dhar, DK.、Nakamoto, T.、Kotoh, T.、Takano, M.、Soma, G-I、Nagasue, N：“肿瘤坏死因子受体在结直肠腺癌中的预后意义”抗癌研究。

Identification and characterization of Fugu orthologues of mammalian interleukin-12 subunits

• DOI: 10.1007/s00251-003-0582-9
• 发表时间: 2003-07
• 期刊: Immunogenetics
• 影响因子: 3.2
• 作者: Y. Yoshiura;I. Kiryu;A. Fujiwara;H. Suetake;Yuzuru Suzuki;T. Nakanishi;M. Ototake

Inherent potential for production of tumor necrosis factor-□ by human intestinal macrophages.

人类肠道巨噬细胞产生肿瘤坏死因子-□的固有潜力。

• 发表时间: 2006
• 期刊: Int J Colorectal Dis. 21
• 作者: Nakata;K.;H.Inagawa;T.Nishizawa;T.Honda;C.Kohchi;Y.Tonomoto;H.Yoshimura;N.Nagase;S.Natori;H.Terada;G-I.Soma
• 通讯作者: G-I.Soma