Molecular Biology

, Volume 53, Issue 2, pp 256–266 | Cite as

Teleost Type 2 Interleukin-1 Receptor (IL-1R2) from the Spotted Halibut (Verasper variegatus): 3D Structure and a Role in Immune Response

  • Z. LiEmail author
  • X. M. Liu
  • A. Y. Li
  • X. X. Du
  • X. B. Wang
  • J. X. Liu
  • Z. G. Wang
  • Q. Q. Zhang
  • H. Y. YuEmail author


The type 2 interleukin-1 receptor (IL-1R2) is one of natural IL-1β singling inhibitors in mammals. We cloned and sequenced the IL-1R2 gene in V. variegatus (VvIL-1R2). The phylogenetic analysis showed that the molecular structure VvIL-1R2 is similar to that of its orthologues in other vertebrates. The expression levels of VvIL-1R2 are relatively high in the peripheral blood leukocytes (PBLs), gill, and spleen. In addition, peculiar expression patterns for his molecule were detected at various developmental stages, implying that in flatfishes the IL-1R2 may have be important for embryonic development and metamorphosis. In PBLs, the treatment with pathogen-associated molecular patterns (PAMPs) induced a significant and rapid up-regulation of VvIL-1R2, pointing at its involvement in the immune responses against bacterial and viral pathogens.


IL-1R2 Verasper variegatus metamorphosis 3D modeling PAMPs 


  1. 1.
    Netea M.G., Nold-Petry C.A., Nold M.F., Joosten L.A.B., Opitz B., van der Meer J.H.M., van de Veerdonk F.L., Ferwerda G., Heinhuis B., Devesa I., Funk C.J., Mason R.J., Kullberg B.J., Rubartelli A., van der Meer J.W.M., Dinarello C.A. 2009. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood. 113, 2324‒2335.CrossRefGoogle Scholar
  2. 2.
    Farasat S., Aksentijevich I., Toro J.R. 2008. Autoinflammatory diseases: Clinical and genetic advances. Arch. Dermatol. 144, 392‒402.CrossRefGoogle Scholar
  3. 3.
    Buss H., Dorrie A., Schmitz M.L., Hoffmann E., Resch K., Kracht M. 2004. Constitutive and interleukin-1-inducible phosphorylation of p65 NF-κB at serine 536 is mediated by multiple protein kinases, including IκB kinase IKKα, IKKβ, IKKε, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase, and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. J. Biol. Chem. 279, 55633‒55643.CrossRefGoogle Scholar
  4. 4.
    Molto A., Olive A. 2010. Anti-IL-1 molecules: New comers and new indications. Joint Bone Spine. 77, 102‒107.CrossRefGoogle Scholar
  5. 5.
    Li X., Qin J. 2005. Modulation of Toll-interleukin 1 receptor mediated signaling. J. Mol. Med. 83, 258‒266.CrossRefGoogle Scholar
  6. 6.
    Dower S.K., Kronheim S.R., March C.J., Conlon P.J., Hopp T.P., Gillis S., Urdal D.L. 1985. Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J. Exp. Med. 162, 501‒515.CrossRefGoogle Scholar
  7. 7.
    Chin J., Cameron P.M., Rupp E., Schmidt J.A. 1987. Identification of a high-affinity receptor for native human interleukin 1 beta and interleukin 1 alpha on normal human lung fibroblasts. J. Exp. Med. 165, 70‒86.CrossRefGoogle Scholar
  8. 8.
    McMahan C.J., Slack J.L., Mosley B., Cosman D., Lupton S.D., Brunton L.L., Grubin C.E., Wignall J.M., Jenkins N.A., Brannan C.I. 1991. A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J. 10, 2821‒2832.CrossRefGoogle Scholar
  9. 9.
    Sangrador-Vegas A., Martin S.A., O’Dea P.G., Smith T.J. 2000. Cloning and characterization of the rainbow trout (Oncorhynchus mykiss) type II interleukin-1 receptor cDNA. Eur. J. Biochem. 267, 7031‒7037.CrossRefGoogle Scholar
  10. 10.
    Lopez-Castejon G., Sepulcre M.P., Roca F.J., Castellana B., Planas J.V., Meseguer J., Mulero V. 2007. The type II interleukin-1 receptor (IL-1RII) of the bony fish gilthead seabream Sparus aurata is strongly induced after infection and tightly regulated at transcriptional and post-transcriptional levels. Mol. Immunol. 44, 2772‒2780.CrossRefGoogle Scholar
  11. 11.
    Fan Y., Li S., Qi J., Zeng L., Zhong Q., Zhang Q. 2010. Cloning and characterization of type II interleukin-1 receptor cDNA from Japanese flounder (Paralichthys olivaceus). Comp. Biochem. Physiol. B: Biochem. Mol. Biol. 157, 59‒65.CrossRefGoogle Scholar
  12. 12.
    Morrison R.N., Young N.D., Nowak B.F. 2012. Description of an Atlantic salmon (Salmo salar L.) type II interleukin-1 receptor cDNA and analysis of interleukin-1 receptor expression in amoebic gill disease-affected fish. Fish Shellfish Immunol. 32, 1185‒1190.CrossRefGoogle Scholar
  13. 13.
    Yang X., Wang S., Du L., Yang K., Wang X., Zhang A., Zhou H. 2013. Molecular and functional characterization of IL-1 receptor type 2 in grass carp: A potent inhibitor of IL-1β signaling in head kidney leukocytes. Dev. Comp. Immunol. 41, 738‒745.CrossRefGoogle Scholar
  14. 14.
    Xu Y., Liu X., Liao M., Wang H., Wang Q. 2012. Molecular cloning and differential expression of three GnRH genes during ovarian maturation of spotted halibut, Verasper variegatus. J. Exp. Zool. A: Ecolog. Genet. Physiol. 317, 434‒446.CrossRefGoogle Scholar
  15. 15.
    Zhou Z., Zhang B., Sun L. 2014. Poly(I:C) induces antiviral immune responses in Japanese flounder (Paralichthys olivaceus) that require TLR3 and MDA5 and is negatively regulated by Myd88. PLoS One. 9, e112918.CrossRefGoogle Scholar
  16. 16.
    Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. 1986. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc. Natl. Acad. Sci. U. S. A. 83, 1670‒1674.CrossRefGoogle Scholar
  17. 17.
    Sachs A.B. 1993. Messenger RNA degradation in eukaryotes. Cell. 74, 413‒421.CrossRefGoogle Scholar
  18. 18.
    Singer S.J. 1990. The structure and insertion of integral proteins in membranes. Annu. Rev. Cell Biol. 6, 247‒296.CrossRefGoogle Scholar
  19. 19.
    Kishimoto T., Taga T., Akira S. 1994. Cytokine signal transduction. Cell. 76, 253‒262.CrossRefGoogle Scholar
  20. 20.
    Luheshi G., Hopkins S.J., Lefeuvre R.A., Dascombe M.J., Ghiara P., Rothwell N.J. 1993. Importance of brain IL-1 type II receptors in fever and thermogenesis in the rat. Am. J. Physiol. 265, 585‒591.Google Scholar
  21. 21.
    Mirtella A., Tringali G., Guerriero G., Ghiara P., Parente L., Preziosi P., Navarra P. 1995. Evidence that the interleukin-1 beta-induced prostaglandin E2 release from rat hypothalamus is mediated by type I and type II interleukin-1 receptors. J. Neuroimmunol. 61, 171‒177.CrossRefGoogle Scholar
  22. 22.
    Giri J.G., Kincade P.W., Mizel S.B. 1984. Interleukin 1-mediated induction of kappa-light chain synthesis and surface immunoglobulin expression on pre-B cells. J. Immunol. 132, 223‒228.Google Scholar
  23. 23.
    Horuk R., McCubrey J.A. 1989. The interleukin-1 receptor in Raji human B-lymphoma cells. Molecular characterization and evidence for receptor-mediated activation of gene expression. Biochem. J. 260, 657‒663.CrossRefGoogle Scholar
  24. 24.
    Greenfeder S.A., Nunes P., Kwee L., Labow M., Chizzonite R.A., Ju G. 1995. Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J. Biol. Chem. 270, 13757‒13765.CrossRefGoogle Scholar
  25. 25.
    Heguy A., Baldari C.T., Macchia G., Telford J.L., Melli M. 1992. Amino acids conserved in interleukin-1 receptors (IL-1Rs) and the Drosophila Toll protein are essential for IL-1R signal transduction. J. Biol. Chem. 267, 2605‒2609.Google Scholar
  26. 26.
    Kuno K., Okamoto S., Hirose K., Murakami S., Matsushima K. 1993. Structure and function of the intracellular portion of the mouse interleukin 1 receptor (type I). Determining the essential region for transducing signals to activate the interleukin 8 gene. J. Biol. Chem. 268, 13510‒13518.Google Scholar
  27. 27.
    Marchler-Bauer A., Derbyshire M.K., Gonzales N.R., Lu S., Chitsaz F., Geer L.Y., Geer R.C., He J., Gwadz M., Hurwitz D.I., Lanczycki C.J., Lu F., Marchler G.H., Song J.S., Thanki N., et al. 2015. CDD: NCBI’s conserved domain database. Nucleic Acids Res. 43, 222‒226.CrossRefGoogle Scholar
  28. 28.
    Marchler-Bauer A., Lu S., Anderson J.B., Chitsaz F., Derbyshire M.K., DeWeese-Scott C., Fong J.H., Geer L.Y., Geer R.C., Gonzales N.R., Gwadz M., Hurwitz D.I., Jackson J.D., Ke Z., et al. 2011. CDD: A Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res. 39, 225‒229.CrossRefGoogle Scholar
  29. 29.
    Marchler-Bauer A., Anderson J.B., Chitsaz F., Derbyshire M.K., DeWeese-Scott C., Fong J.H., Geer L.Y., Geer R.C., Gonzales N.R., Gwadz M., He S., Hurwitz D.I., Jackson J.D., Ke Z., Lanczycki C.J., et al. 2009. CDD: Specific functional annotation with the Conserved Domain Database. Nucleic Acids Res. 37, 205‒210.CrossRefGoogle Scholar
  30. 30.
    Marchler-Bauer A., Bryant S.H. 2004. CD-Search: Protein domain annotations on the fly. Nucleic Acids Res. 32, 327‒331.CrossRefGoogle Scholar
  31. 31.
    Hawiger J. 2001. Innate immunity and inflammation: A transcriptional paradigm. Immunol. Res. 23, 99‒109.CrossRefGoogle Scholar
  32. 32.
    Moro J.A., Carretero J., Alonso M.I., Martin C., Gato A., Mano A.D.L. 2008. Prenatal expression of interleukin 1beta and interleukin 6 in the rat pituitary gland. Cytokine. 44, 315‒322.CrossRefGoogle Scholar
  33. 33.
    Bagu E.T., Gordon J.R., Rawlings N.C. 2010. Post-natal changes in testicular concentrations of interleukin-1 alpha and beta and interleukin-6 during sexual maturation in bulls. Reprod. Domest. Anim. 45, 336‒341.CrossRefGoogle Scholar
  34. 34.
    West D.A., James N.H., Cosulich S.C., Holden P.R., Brindle R., Rolfe M., Roberts R.A. 1999. Role for tumor necrosis factor alpha receptor 1 and interleukin-1 receptor in the suppression of mouse hepatocyte apoptosis by the peroxisome proliferator nafenopin. Hepatology. 30, 1417‒1424.CrossRefGoogle Scholar
  35. 35.
    Liu X., Min L., Duan H., Shi R., Zhang W., Hong S., Tu C. 2015. Short hairpin RNA (shRNA) of type 2 interleukin-1 receptor (IL1R2) inhibits the proliferation of human osteosarcoma U-2 OS cells. Med. Oncol. 32, 364.CrossRefGoogle Scholar
  36. 36.
    Zieleniewski W., Zieleniewski J., Stepien H. 1995. Effect of interleukin-1a, IL-1b and IL-1 receptor antibody on the proliferation and steroidogenesis of regenerating rat adrenal cortex. Exp. Clin. Endocrinol. Diabetes. 103, 373‒377.CrossRefGoogle Scholar
  37. 37.
    Wang Y., Bu L., Yang L., Li H., Zhang S. 2016. Identification and functional characterization of fish-egg lectin in zebrafish. Fish Shellfish Immunol. 52, 23‒30.CrossRefGoogle Scholar
  38. 38.
    Kim B., Nam B., Kim J., Park H., Song J., Park C. 2011. Molecular characterisation and expression analysis of a fish-egg lectin in rock bream, and its response to bacterial or viral infection. Fish Shellfish Immunol. 31, 1201‒1207.CrossRefGoogle Scholar
  39. 39.
    Li H., Fan J., Liu S., Yang Q., Mu G., He C. 2012. Characterization of a myostatin gene (MSTN1. from spotted halibut (Verasper variegatus) and association between its promoter polymorphism and individual growth performance. Comp. Biochem. Physiol. B: Biochem. Mol. Biol. 161, 315‒322.CrossRefGoogle Scholar
  40. 40.
    Li H., Jiang L., Han J., Su H., Yang Q., He C. 2011. Major histocompatibility complex class IIA and IIB genes of the spotted halibut Verasper variegatus: genomic structure, molecular polymorphism, and expression analysis. Fish Physiol. Biochem. 37, 767‒780.CrossRefGoogle Scholar
  41. 41.
    Power D.M., Llewellyn L., Faustino M., Nowell M.A., Bjornsson B.T., Einarsdottir I.E., Canario A.V., Sweeney G.E. 2001. Thyroid hormones in growth and development of fish. Comp. Biochem. Physiol. C: Toxicol. Pharmacol. 130, 447‒459.Google Scholar
  42. 42.
    Campinho M.A., Silva N., Sweeney G.E., Power D.M. 2006. Molecular, cellular and histological changes in skin from a larval to an adult phenotype during bony fish metamorphosis. Cell Tissue Res. 327, 267‒284.CrossRefGoogle Scholar
  43. 43.
    Marchand O., Duffraisse M., Triqueneaux G., Safi R., Laudet V. 2004. Molecular cloning and developmental expression patterns of thyroid hormone receptors and T3 target genes in the turbot (Scophtalmus maximus) during post-embryonic development. Gen. Comp. Endocrinol. 135, 345‒357.CrossRefGoogle Scholar
  44. 44.
    Yamano K., Miwa S. 1998. Differential gene expression of thyroid hormone receptor alpha and beta in fish development. Gen. Comp. Endocrinol. 109, 75‒85.CrossRefGoogle Scholar
  45. 45.
    Yamano K., Araki K., Sekikawa K., Inui Y. 1994. Cloning of thyroid hormone receptor genes expressed in metamorphosing flounder. Dev. Genet. 15, 378‒382.CrossRefGoogle Scholar
  46. 46.
    Inui Y., Miwa S. 1985. Thyroid hormone induces metamorphosis of flounder larvae. Gen. Comp. Endocrinol. 60, 450‒454.CrossRefGoogle Scholar
  47. 47.
    de Jesus E.G., Hirano T., Inui Y. 1991. Changes in cortisol and thyroid hormone concentrations during early development and metamorphosis in the Japanese flounder, Paralichthys olivaceus. Gen. Comp. Endocrinol. 82, 369‒376.CrossRefGoogle Scholar
  48. 48.
    Liu Y., Chan W. 2002. Thyroid hormones are important for embryonic to larval transitory phase in zebrafish. Differentiation. 70, 36‒45.CrossRefGoogle Scholar
  49. 49.
    Klaren P.H.M., Wunderink Y.S., Yufera M., Mancera J.M., Flik G. 2008. The thyroid gland and thyroid hormones in Senegalese sole (Solea senegalensis) during early development and metamorphosis. Gen. Comp. Endocrinol. 155, 686‒694.CrossRefGoogle Scholar
  50. 50.
    Svenson M., Kayser L., Hansen M.B., Rasmussen Å.K., Bendtzen K. 1991. Interleukin-1 receptors on human thyroid cells and on the rat thyroid cell line FRTL-5. Cytokine. 3, 125‒130.CrossRefGoogle Scholar
  51. 51.
    Van der P. T., Van Zee K.J., Endert E., Coyle S.M., Stiles D.M., Pribble J.P., Catalano M.A., Moldawer L.L., Lowry S.F. 1995. Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man. J. Clin. Endocrinol. Metabolism. 80, 1341‒1346.Google Scholar
  52. 52.
    Zerek-Melen G., Zylinska K., Fryczak J., Mucha S., Stepien H. 1994. Influence of interleukin 1 and antihuman interleukin 1 receptor antibody on the growth and function of the thyroid gland in rats. Eur. J. Endocrinol. 131, 531‒534.CrossRefGoogle Scholar
  53. 53.
    Meixenberger K., Pache F., Eitel J., Schmeck B., Hippenstiel S., Slevogt H., N’Guessan P., Witzenrath M., Netea M.G., Chakraborty T., Suttorp N., Opitz B. 2010. Listeria monocytogenes-infected human peripheral blood mononuclear cells produce IL-1beta, depending on listeriolysin O and NLRP3. J. Immunol. 184, 922‒930.CrossRefGoogle Scholar
  54. 54.
    Bourigault M., Segueni N., Rose S., Court N., Vacher R., Vasseur V., Erard F., Le Bert M., Garcia I., Iwakura Y., Jacobs M., Ryffel B., Quesniaux V.F.J. 2013. Relative contribution of IL-1alpha, IL-1beta and TNF to the host response to Mycobacterium tuberculosis and attenuated M. bovis BCG. Immun. Infl. Disease. 1, 47‒62.CrossRefGoogle Scholar
  55. 55.
    Zhou Y., Zhao D., Yue R., Khan S.H., Shah S.Z.A., Yin X., Yang L., Zhang Z., Zhou X. 2015. Inflammasomes-dependent regulation of IL-1beta secretion induced by the virulent Mycobacterium bovis Beijing strain in THP-1 macrophages. Antonie van Leeuwenhoek. 108, 163‒171.CrossRefGoogle Scholar
  56. 56.
    Covello J.M., Bird S., Morrison R.N., Battaglene S.C., Secombes C.J., Nowak B.F. 2009. Cloning and expression analysis of three striped trumpeter (Latris lineata) pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-8, in response to infection by the ectoparasitic, Chondracanthus goldsmidi. Fish Shellfish Immunol. 26, 773‒786.CrossRefGoogle Scholar
  57. 57.
    Jang C., Choi J., Byun M., Jue D. 2006. Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology. 45, 703‒710.CrossRefGoogle Scholar
  58. 58.
    Stylianou E., O’Neill L.A., Rawlinson L., Edbrooke M.R., Woo P., Saklatvala J. 1992. Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes. J. Biol. Chem. 267, 15836‒15841.Google Scholar
  59. 59.
    Colotta F., Re F., Muzio M., Bertini R., Polentarutti N., Sironi M., Giri J.G., Dower S.K., Sims J.E., Mantovani A. 1993. Interleukin-1 type II receptor: A decoy target for IL-1 that is regulated by IL-4. Science. 261, 472‒475.CrossRefGoogle Scholar
  60. 60.
    Sims J.E., Gayle M.A., Slack J.L., Alderson M.R., Bird T.A., Giri J.G., Colotta F., Re F., Mantovani A., Shanebeck K. 1993. Interleukin 1 signaling occurs exclusively via the type I receptor. Proc. Natl. Acad. Sci. U. S. A. 90, 6155‒6159.CrossRefGoogle Scholar
  61. 61.
    Peters V.A., Joesting J.J., Freund G.G. 2013. IL-1 receptor 2 (IL-1R2) and its role in immune regulation. Brain Behav. Immunity. 32, 1‒8.CrossRefGoogle Scholar
  62. 62.
    Schreuder H., Tardif C., Trump-Kallmeyer S., Soffientini A., Sarubbi E., Akeson A., Bowlin T., Yanofsky S., Barrett R.W. 1997. A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist. Nature. 386, 194‒200.CrossRefGoogle Scholar

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© Pleiades Publishing, Inc. 2019

Authors and Affiliations

  • Z. Li
    • 1
    • 2
    Email author
  • X. M. Liu
    • 2
  • A. Y. Li
    • 2
  • X. X. Du
    • 2
  • X. B. Wang
    • 2
  • J. X. Liu
    • 2
  • Z. G. Wang
    • 2
  • Q. Q. Zhang
    • 2
  • H. Y. Yu
    • 2
    Email author
  1. 1.School of Agriculture, Ludong UniversityYantaiChina
  2. 2.Key Laboratory of Marine Genetics and Breeding, Ministry of Education, College of Marine Life Science, Ocean University of ChinaQingdaoChina

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