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

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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.