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Identification of a Novel IL-1 Cytokine Family Member in Teleost Fish¹

Tiehui Wang^*, Steve Bird^*, Antonis Koussounadis, Jason W. Holland^*, Allison Carrington^*, Jun Zou^* and Christopher J. Secombes^2,*

^* Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom; and Bioinformatics Group, Department of Computer Science, University College London, London, United Kingdom

A novel IL-1 family member (nIL-1F) has been discovered in fish, adding a further member to this cytokine family. The unique gene organization of nIL-1F, together with its location in the genome and low homology to known family members, suggests that this molecule is not homologous to known IL-1F. Nevertheless, it contains a predicted C-terminal β-trefoil structure, an IL-1F signature region within the final exon, a potential IL-1 converting enzyme cut site, and its expression level is clearly increased following infection, or stimulation of macrophages with LPS or IL-1β. A thrombin cut site is also present and may have functional relevance. The C-terminal recombinant protein antagonized the effects of rainbow trout rIL-1β on inflammatory gene expression in a trout macrophage cell line, suggesting it is an IL-1β antagonist. Modeling studies confirmed that nIL-1F has the potential to bind to the trout IL-1RI receptor protein, and may be a novel IL-1 receptor antagonist.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the European Community with Contracts 513692 (Aquafirst), Q5RS-2001-002211 (Stressgenes), and 007103 (Improved Immunity of Aquacultured Animals, IMAQUANIM).

² Address correspondence and reprint requests to Dr. Christopher J. Secombes, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, U.K. E-mail address: c.secombes{at}abdn.ac.uk

³ Abbreviations used in this paper: IL-1F, IL-1 family; AcP, accessory protein; BLAST, basic local alignment search tool; CHO, Chinese hamster ovary; COX, cyclooxygenase; EF-1, elongation factor-1; ICE, IL-1 converting enzyme; nIL-1F, novel IL-1 family; pI, isoelectric point; UTR, untranslated region.