Skip to main content
Log in

Multiple and highly divergent IL-11 genes in teleost fish

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Interleukin-11 (IL-11) is a key cytokine in the regulation of proliferation and differentiation of hematopoietic progenitors and is also involved in bone formation, adipogenesis, and protection of mucosal epithelia. Despite this prominent role in diverse physiological processes, IL-11 has been described in only four mammalian species, and recently, in rainbow trout (Oncorhynchus mykiss). Here we report the presence of IL-11 in common carp (Cyprinus carpio), a bony fish species related to zebrafish. IL-11 is expressed in most carp organs and tissues. In vitro expression of IL-11 in cultured macrophages is enhanced by stimulation with lipopolysaccharide and is markedly inhibited by cortisol. A detailed and systematic scan of several fish genome databases confirms that IL-11 is present in all fish, but also reveals the presence of a second, substantially different IL-11 gene in the genomes of phylogenetically distant fish species. We designated both fish paralogues IL-11a and IL-11b. Although sequence identity between fish IL-11a and IL-11b peptides is low, the conservation of their gene structures supplemented by phylogenetic analyses clearly illustrate the orthology of both IL-11a and IL-11b genes of fish with mammalian IL-11. The presence of IL-11 genes in fish demonstrates its importance throughout vertebrate evolution, although the presence of duplicate and divergent IL-11 genes differs from the single IL-11 gene that exists in mammals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Angeli A, Dovio A, Sartori ML, Masera RG, Ceoloni B, Prolo P, Racca S, Chiappelli F (2002) Interactions between glucocorticoids and cytokines in the bone microenvironment. Ann NY Acad Sci 966:97–107

    Article  PubMed  CAS  Google Scholar 

  • Aparicio S, Chapman J, Stupka E, Putnam N, Chia JM, Dehal P, Christoffels A, Rash S, Hoon S, Smit A, Gelpke MD, Roach J, Oh T, Ho IY, Wong M, Detter C, Verhoef F, Predki P, Tay A, Lucas S, Richardson P, Smith SF, Clark MS, Edwards YJ, Doggett N, Zharkikh A, Tavtigian SV, Pruss D, Barnstead M, Evans C, Baden H, Powell J, Glusman G, Rowen L, Hood L, Tan YH, Elgar G, Hawkins T, Venkatesh B, Rokhsar D, Brenner S (2002) Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science 297:1301–1310

    Article  PubMed  CAS  Google Scholar 

  • Barton VA, Hudson KR, Heath JK (1999) Identification of three distinct receptor binding sites of murine interleukin-11. J Biol Chem 274:5755–5761

    Article  PubMed  CAS  Google Scholar 

  • Barton VA, Hall MA, Hudson KR, Heath JK (2000) Interleukin-11 signals through the formation of a hexameric receptor complex. J Biol Chem 275:36197–36203

    Article  PubMed  CAS  Google Scholar 

  • Bazan JF (1990) Haematopoietic receptors and helical cytokines. Immunol Today 11:350–354

    Article  PubMed  CAS  Google Scholar 

  • Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340:783–795

    Article  PubMed  CAS  Google Scholar 

  • Chong SW, Emelyanov A, Gong Z, Korzh V (2001) Expression pattern of two zebrafish genes, cxcr4a and cxcr4b. Mech Dev 109:347–354

    Article  PubMed  CAS  Google Scholar 

  • Chou CF, Tohari S, Brenner S, Venkatesh B (2004) Erythropoietin gene from a teleost fish, Fugu rubripes. Blood 104:1498–1503

    Article  PubMed  CAS  Google Scholar 

  • Czupryn MJ, McCoy JM, Scoble HA (1995) Structure-function relationships in human interleukin-11. Identification of regions involved in activity by chemical modification and site-directed mutagenesis. J Biol Chem 270:978–985

    Article  PubMed  CAS  Google Scholar 

  • Du XX, Williams DA (1994) Interleukin-11: a multifunctional growth factor derived from the hematopoietic microenvironment. Blood 83:2023–2030

    PubMed  CAS  Google Scholar 

  • Du X, Williams DA (1997) Interleukin-11: review of molecular, cell biology, and clinical use. Blood 89:3897–3908

    PubMed  CAS  Google Scholar 

  • Du XX, Keller D, Maze R, Williams DA (1993a) Comparative effects of in vivo treatment using interleukin-11 and stem cell factor on reconstitution in mice after bone marrow transplantation. Blood 82:1016–1022

    PubMed  CAS  Google Scholar 

  • Du XX, Neben T, Goldman S, Williams DA (1993b) Effects of recombinant human interleukin-11 on hematopoietic reconstitution in transplant mice: acceleration of recovery of peripheral blood neutrophils and platelets. Blood 81:27–34

    PubMed  CAS  Google Scholar 

  • Du XX, Doerschuk CM, Orazi A, Williams DA (1994) A bone marrow stromal-derived growth factor, interleukin-11, stimulates recovery of small intestinal mucosal cells after cytoablative therapy. Blood 83:33–37

    PubMed  CAS  Google Scholar 

  • Du XX, Scott D, Yang ZX, Cooper R, Xiao XL, Williams DA (1995) Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures. Blood 86:128–134

    PubMed  CAS  Google Scholar 

  • Du X, Everett ET, Wang G, Lee WH, Yang Z, Williams DA (1996) Murine interleukin-11 (IL-11) is expressed at high levels in the hippocampus and expression is developmentally regulated in the testis. J Cell Physiol 168:362–372

    Article  PubMed  CAS  Google Scholar 

  • Du X, Liu Q, Yang Z, Orazi A, Rescorla FJ, Grosfeld JL, Williams DA (1997) Protective effects of interleukin-11 in a murine model of ischemic bowel necrosis. Am J Physiol 272:G545-G552

    PubMed  CAS  Google Scholar 

  • Elias JA, Tang W, Horowitz MC (1995) Cytokine and hormonal stimulation of human osteosarcoma interleukin-11 production. Endocrinology 136:489–498

    Article  PubMed  CAS  Google Scholar 

  • Engelsma MY, Stet RJ, Saeij JP, Verburg-van Kemenade BM (2003) Differential expression and haplotypic variation of two interleukin-1beta genes in the common carp (Cyprinus carpio L.). Cytokine 22:21–32

    Article  PubMed  CAS  Google Scholar 

  • Force A, Lynch M, Pickett FB, Amores A, Yan YL, Postlethwait J (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151:1531–1545

    PubMed  CAS  Google Scholar 

  • Fujiki K, Nakao M, Dixon B (2003) Molecular cloning and characterisation of a carp (Cyprinus carpio) cytokine-like cDNA that shares sequence similarity with IL-6 subfamily cytokines CNTF, OSM and LIF. Dev Comp Immunol 27:127–136

    Article  PubMed  CAS  Google Scholar 

  • Hubbard T, Andrews D, Caccamo M, Cameron G, Chen Y, Clamp M, Clarke L, Coates G, Cox T, Cunningham F, Curwen V, Cutts T, Down T, Durbin R, Fernandez-Suarez XM, Gilbert J, Hammond M, Herrero J, Hotz H, Howe K, Iyer V, Jekosch K, Kahari A, Kasprzyk A, Keefe D, Keenan S, Kokocinsci F, London D, Longden I, McVicker G, Melsopp C, Meidl P, Potter S, Proctor G, Rae M, Rios D, Schuster M, Searle S, Severin J, Slater G, Smedley D, Smith J, Spooner W, Stabenau A, Stalker J, Storey R, Trevanion S, Ureta-Vidal A, Vogel J, White S, Woodwark C, Birney E (2005) Ensembl 2005. Nucleic Acids Res 33:D447–D453

    Article  PubMed  CAS  Google Scholar 

  • Huising MO, Guichelaar T, Hoek C, Verburg-van Kemenade BM, Flik G, Savelkoul HF, Rombout JH (2003) Increased efficacy of immersion vaccination in fish with hyperosmotic pretreatment. Vaccine 21:4178–4493

    Article  PubMed  CAS  Google Scholar 

  • Huising MO, Metz JR, van Schooten C, Taverne-Thiele AJ, Hermsen T, Verburg-van Kemenade BM, Flik G (2004a) Structural characterisation of a cyprinid (Cyprinus carpio L.) CRH, CRH-BP and CRH-R1, and the role of these proteins in the acute stress response. J Mol Endocrinol 32:627–648

    Article  PubMed  CAS  Google Scholar 

  • Huising MO, van der Meulen T, Flik G, Verburg-van Kemenade BM (2004b) Three novel carp CXC chemokines are expressed early in ontogeny and at nonimmune sites. Eur J Biochem 271:4094–4106

    Article  PubMed  CAS  Google Scholar 

  • Jaillon O, Aury JM, Brunet F, Petit JL, Stange-Thomann N, Mauceli E, Bouneau L, Fischer C, Ozouf-Costaz C, Bernot A, Nicaud S, Jaffe D, Fisher S, Lutfalla G, Dossat C, Segurens B, Dasilva C, Salanoubat M, Levy M, Boudet N, Castellano S, Anthouard V, Jubin C, Castelli V, Katinka M, Vacherie B, Biemont C, Skalli Z, Cattolico L, Poulain J, De Berardinis V, Cruaud C, Duprat S, Brottier P, Coutanceau JP, Gouzy J, Parra G, Lardier G, Chapple C, McKernan KJ, McEwan P, Bosak S, Kellis M, Volff JN, Guigo R, Zody MC, Mesirov J, Lindblad-Toh K, Birren B, Nusbaum C, Kahn D, Robinson-Rechavi M, Laudet V, Schachter V, Quetier F, Saurin W, Scarpelli C, Wincker P, Lander ES, Weissenbach J, Roest Crollius H (2004) Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature 431:946–957

    Article  PubMed  Google Scholar 

  • Keller DC, Du XX, Srour EF, Hoffman R, Williams DA (1993) Interleukin-11 inhibits adipogenesis and stimulates myelopoiesis in human long-term marrow cultures. Blood 82:1428–1435

    PubMed  CAS  Google Scholar 

  • Kiessling S, Muller-Newen G, Leeb SN, Hausmann M, Rath HC, Strater J, Spottl T, Schlottmann K, Grossmann J, Montero-Julian FA, Scholmerich J, Andus T, Buschauer A, Heinrich PC, Rogler G (2004) Functional expression of the interleukin-11 receptor alpha-chain and evidence of antiapoptotic effects in human colonic epithelial cells. J Biol Chem 279:10304–10315

    Article  PubMed  CAS  Google Scholar 

  • Kim CH, Cheng SL, Kim GS (1999) Effects of dexamethasone on proliferation, activity, and cytokine secretion of normal human bone marrow stromal cells: possible mechanisms of glucocorticoid-induced bone loss. J Endocrinol 162:371–379

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi S, Teramura M, Sugawara I, Oshimi K, Mizoguchi H (1993) Interleukin-11 acts as an autocrine growth factor for human megakaryoblastic cell lines. Blood 81:889–893

    PubMed  CAS  Google Scholar 

  • Kumar S, Hedges SB (1998) A molecular timescale for vertebrate evolution. Nature 392:917–920

    Article  PubMed  CAS  Google Scholar 

  • Kumar S, Tamura K, Jakobsen IB, Nei M (2001) MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244–1245

    Article  PubMed  CAS  Google Scholar 

  • Maier R, Ganu V, Lotz M (1993) Interleukin-11, an inducible cytokine in human articular chondrocytes and synoviocytes, stimulates the production of the tissue inhibitor of metalloproteinases. J Biol Chem 268:21527–21532

    PubMed  CAS  Google Scholar 

  • Mehler MF, Rozental R, Dougherty M, Spray DC, Kessler JA (1993) Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Nature 362:62–65

    Article  PubMed  CAS  Google Scholar 

  • Neben TY, Loebelenz J, Hayes L, McCarthy K, Stoudemire J, Schaub R, Goldman SJ (1993) Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice. Blood 81:901–908

    PubMed  CAS  Google Scholar 

  • Ozaki K, Leonard WJ (2002) Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem 277:29355–29358

    Article  PubMed  CAS  Google Scholar 

  • Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O'Hara RM Jr, Leary AC, Sibley B, Clark SC, Williams DA et al (1990) Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci U S A 87:7512–7516

    Article  PubMed  CAS  Google Scholar 

  • Pearson WR, Lipman DJ (1988) Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A 85:2444–2448

    Article  PubMed  CAS  Google Scholar 

  • Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    Article  PubMed  CAS  Google Scholar 

  • Quesniaux VF, Clark SC, Turner K, Fagg B (1992) Interleukin-11 stimulates multiple phases of erythropoiesis in vitro. Blood 80:1218–1223

    PubMed  CAS  Google Scholar 

  • Redlich CA, Gao X, Rockwell S, Kelley M, Elias JA (1996) IL-11 enhances survival and decreases TNF production after radiation-induced thoracic injury. J Immunol 157:1705–1710

    PubMed  CAS  Google Scholar 

  • Saeij JP, Verburg-van Kemenade LB, van Muiswinkel WB, Wiegertjes GF (2003) Daily handling stress reduces resistance of carp to Trypanoplasma borreli: in vitro modulatory effects of cortisol on leukocyte function and apoptosis. Dev Comp Immunol 27:233–245

    Article  PubMed  CAS  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  • Takeuchi Y, Watanabe S, Ishii G, Takeda S, Nakayama K, Fukumoto S, Kaneta Y, Inoue D, Matsumoto T, Harigaya K, Fujita T (2002) Interleukin-11 as a stimulatory factor for bone formation prevents bone loss with advancing age in mice. J Biol Chem 277:49011–49018

    Article  PubMed  CAS  Google Scholar 

  • Taylor JS, Braasch I, Frickey T, Meyer A, Van de Peer Y (2003) Genome duplication, a trait shared by 22000 species of ray-finned fish. Genome Res 13:382–390

    Article  PubMed  CAS  Google Scholar 

  • Teramura M, Kobayashi S, Hoshino S, Oshimi K, Mizoguchi H (1992) Interleukin-11 enhances human megakaryocytopoiesis in vitro. Blood 79:327–331

    PubMed  CAS  Google Scholar 

  • Trepicchio WL, Bozza M, Pedneault G, Dorner AJ (1996) Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J Immunol 157:3627–3634

    PubMed  CAS  Google Scholar 

  • Wang T, Holland JW, Bols N, Secombes CJ (2005) Cloning and expression of the first nonmammalian interleukin-11 gene in rainbow trout Oncorhynchus mykiss. FEBS J 272:1136–1147

    Article  PubMed  CAS  Google Scholar 

  • Waxman AB, Einarsson O, Seres T, Knickelbein RG, Warshaw JB, Johnston R, Homer RJ, Elias JA (1998) Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation. J Clin Invest 101:1970–1982

    PubMed  CAS  Google Scholar 

  • Waxman AB, Mahboubi K, Knickelbein RG, Mantell LL, Manzo N, Pober JS, Elias JA (2003) Interleukin-11 and interleukin-6 protect cultured human endothelial cells from H2O2-induced cell death. Am J Respir Cell Mol Biol 29:513–522

    Article  PubMed  CAS  Google Scholar 

  • Williams JL, Pipia GG, Datta NS, Long MW (1998) Thrombopoietin requires additional megakaryocyte-active cytokines for optimal ex vivo expansion of megakaryocyte precursor cells. Blood 91:4118–4126

    PubMed  CAS  Google Scholar 

  • Yoshiura Y, Kiryu I, Fujiwara A, Suetake H, Suzuki Y, Nakanishi T, Ototake M (2003) Identification and characterization of Fugu orthologues of mammalian interleukin-12 subunits. Immunogenetics 55:296–306

    Article  PubMed  CAS  Google Scholar 

  • Zheng T, Zhu Z, Wang J, Homer RJ, Elias JA (2001) IL-11: insights in asthma from overexpression transgenic modeling. J Allergy Clin Immunol 108:489–496

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge Mr. Adrie Groeneveld for his excellent technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. M. Lidy Verburg-van Kemenade.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huising, M.O., Kruiswijk, C.P., van Schijndel, J.E. et al. Multiple and highly divergent IL-11 genes in teleost fish. Immunogenetics 57, 432–443 (2005). https://doi.org/10.1007/s00251-005-0012-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-005-0012-2

Keywords

Navigation