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Relationship between interleukin-1 type 1 and 2 receptor gene polymorphisms and the expression level of membrane-bound receptors

Cellular & Molecular Immunology volume 12, pages 222–230 (2015)Cite this article

Abstract

The biological activity of the multifunctional cytokine interleukin-1 (IL-1) is mediated by its receptors. The aim of this study was to determine if an association exists between single nucleotide polymorphisms (SNPs) in the IL-1 type 1 and 2 receptor genes (IL1R1 and IL1R2) and the expression level of membrane-bound IL1Rs on subpopulations of mononuclear cells or serum levels of soluble IL-1 receptors. It was observed that healthy individuals with the genotype TT in SNP rs2234650:C>T had a lower percentage of intact CD14+ monocytes expressing IL1R1 on their surface. The SNP rs4141134:T>C in IL1R2 has also been associated with the percentage of intact CD3+ T cells expressing IL1R2. Furthermore, individuals carrying the CC allele of SNP rs4141134:T>C and the TT allele of SNP rs2071008:T>G in IL1R2 had a lower density of IL1R2s on the surface of CD14+ monocytes in lipopolysaccharide (LPS)-stimulated PBMC cultures. In summary, this study demonstrated that IL-1 receptor gene polymorphisms could be one of the factors influencing the expression of membrane-bound IL-1 receptors (IL1R) on immunocompetent cells.

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References

  1. Dinarello CA . Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 2009; 27: 519–550.

    Article  CAS  Google Scholar 

  2. Gabay C, Lamacchia C, Palmer G . IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol 2010; 6: 232–241.

    Article  CAS  Google Scholar 

  3. Colotta F, Re F, Muzio M, Bertini R, Polentarutti N, Sironi M et al. Interleukin-1 type II receptor: a decoy target for IL-1 that regulated by IL-4. Science 1993; 261: 472–475.

    Article  CAS  Google Scholar 

  4. Sims JE, Gayle MA, Slack JL, Alderson MR, Bird TA, Giri JG et al. Interleukin 1 signaling occurs exclusively via the type I receptor. Proc Natl Acad Sci USA 1993; 90: 6155–6159.

    Article  CAS  Google Scholar 

  5. Dinarello CA . IL-1 receptor type I. In: Oppenheim JJ, Feldmann M, Durum SK, Hirano T, Vilcek J, Nicola NA (ed.) Cytokine Reference: A Compendium of Cytokines and Other Mediators of Host Defense. London: Academic Press, 2001: 1587–1600.

    Google Scholar 

  6. Arend WP, Palmer G, Gabay C . IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev 2008; 223: 20–38.

    Article  CAS  Google Scholar 

  7. Mantovani A, Locati M, Vecchi A, Sozzani S, Allavena P . Decoy receptors: a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol 2001; 22: 328–336.

    Article  CAS  Google Scholar 

  8. Wang M, Windgassen D, Papoutsakis ET . Comparative analysis of transcriptional profiling of CD3+, CD4+ and CD8+ T cells identifies novel immune response players in T-cell activation. BMC Genomics 2008; 9: 225.

    Article  Google Scholar 

  9. Matsushima K, Akahoshi T, Yamada M, Furutani Y, Oppenheim JJ . Properties of a specific interleukin 1 (IL 1) receptor on human Epstein Barr virus-transformed B lymphocytes: identity of the receptor for IL 1-alpha and IL 1-beta. J Immunol 1986; 136: 4496–4502.

    CAS  PubMed  Google Scholar 

  10. Symons JA, Eastgate JA, Duff GW . Purification and characterization of a novel soluble receptor for interleukin 1. J Exp Med 1991; 174: 1251–1254.

    Article  CAS  Google Scholar 

  11. Arend WP, Malyak M, Smith MF Jr, Whisenand TD, Slack JL, Sims JE et al. Binding of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist by soluble IL-1 receptors and levels of soluble IL-1 receptors in synovial fluids. J Immunol 1994; 153: 4766–4774.

    CAS  PubMed  Google Scholar 

  12. Orlando S, Sironi M, Bianchi G, Drummond AH, Boraschi D, Yabes D et al. Role of metalloproteases in the release of the IL-1 type II decoy receptor. J Biol Chem 1997; 272: 31764–31769.

    Article  CAS  Google Scholar 

  13. Liu C, Hart RP, Liu XJ, Clevenger W, Maki RA, de Souza EB . Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA. J Biol Chem 1996; 271: 20965–20972.

    Article  CAS  Google Scholar 

  14. Symons JA, Young PR, Duff GW . Soluble type II interleukin 1 (IL-1) receptor binds and blocks processing of IL-1 beta precursor and loses affinity for IL-1 receptor antagonist. Proc Natl Acad Sci USA 1995; 92: 1714–1718.

    Article  CAS  Google Scholar 

  15. Ye K, Vannier E, Clark BD, Sims JE, Dinarello CA . Three distinct promoters direct transcription of different 5′ untranslated regions of the human interleukin 1 type I receptor: a possible mechanism for control of translation. Cytokine 1996; 8: 421–429.

    Article  CAS  Google Scholar 

  16. Dale M, Nicklin MJ . Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. Genomics 1999; 57: 177–179.

    Article  CAS  Google Scholar 

  17. Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF . Cytokine gene polymorphism in human disease: on-line databases. Genes Immun 1999; 1: 3–19.

    Article  CAS  Google Scholar 

  18. Shastry BS . SNPs: impact on gene function and phenotype. Methods Mol Biol 2009; 578: 3–22.

    Article  CAS  Google Scholar 

  19. Brookes AJ . The essence of SNPs. Gene 1999; 234: 177–186.

    Article  CAS  Google Scholar 

  20. Sennikov SV, Vasilyev FF, Lopatnikova JA, Shkaruba NS, Silkov AN . Polymorphisms in the tumor necrosis factor receptor genes affect the expression levels of membrane-bound type i and type ii receptors. Mediators Inflamm 2014; 2014: 745909.

    Article  Google Scholar 

  21. Reynes J, Portales P, Segondy M, Baillat V, André P, Réant B et al. CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1. J Infect Dis 2000; 181: 927–933.

    Article  CAS  Google Scholar 

  22. Moraga I, Harari D, Schreiber G, Uzé G, Pellegrini S . Receptor density is key to the alpha2/beta interferon differential activities. Mol Cell Biol 2009; 29: 4778–4787.

    Article  CAS  Google Scholar 

  23. Bebes A, Kovács-Sólyom F, Prihoda J, Kui R, Kemény L, Gyulai R . Interleukin-1 receptors are differentially expressed in normal and psoriatic T cells. Mediators Inflamm 2014; 2014: 472625

    Article  Google Scholar 

  24. Böyum A . Separation of leukocytes from blood and bone marrow. Introduction. Scand J Clin Lab Invest 1968; Suppl 97: 7.

    Google Scholar 

  25. Vasilyev FF, Lopatnikova JA, Sennikov SV . Optimized flow cytometry protocol for analysis of surface expression of interleukin-1 receptor types I and II. Cytotechnology 2013; 65: 795–802.

    Article  CAS  Google Scholar 

  26. Maniatis T, Sambrook J, Fritsch EF . Molecular Cloning—A Laboratory Manual. New York: Cold Spring Harbor Press, 1989: 76–85.

    Google Scholar 

  27. Bergholdt R, Karlsen AE, Johannesen J, Hansen PM, Dinarello CA, Nerup J et al. Characterization of polymorphisms of an interleukin 1 receptor type 1 gene (IL1RI) promotor region (P2) and their relation to insulin-dependent diabetes mellitus (IDDM). The Danish Study Group of Diabetes in Childhood. Cytokine 1995; 7: 727–733.

    Article  CAS  Google Scholar 

  28. Saccani S, Polentarutti N, Penton-Rol G, Sims JE, Mantovani A . Divergent effects of LPS on expression of IL-1 receptor family members in mononuclear phagocytes in vitro and in vivo. Cytokine 1998; 10: 773–780.

    Article  CAS  Google Scholar 

  29. Penton-Rol G, Orlando S, Polentarutti N, Bernasconi S, Muzio M, Introna M et al. Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcripts. J Immunol 1999; 162: 2931–2938.

    CAS  PubMed  Google Scholar 

  30. Smith AJ, Humphries SE . Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev 2009; 20: 43–59.

    Article  CAS  Google Scholar 

  31. Hollegaard MV, Bidwell JL . Cytokine gene polymorphism in human disease: on-line databases, Supplement 3. Genes Immun 2006; 7: 269–276.

    Article  CAS  Google Scholar 

  32. Näkki A, Kouhia ST, Saarela J, Harilainen A, Tallroth K, Videman T . Allelic variants of IL1R1 gene associate with severe hand osteoarthritis. BMC Med Genet 2010; 11: 50.

    Article  Google Scholar 

  33. Park SW, Kim MK, Kwon KH, Kim J . Association between a promoter polymorphism (rs2192752, -1028A/C) of interleukin 1 receptor, type I (IL1R1) and location of papillary thyroid carcinoma in a Korean population. Int J Immunogenet 2012; 39: 501–507.

    Article  Google Scholar 

  34. Metcalfe KA, Hitman GA, Pociot F, Bergholdt R, Tuomilehto-Wolf E, Tuomilehto J et al. An association between type 1 diabetes and the interleukin-1 receptor type 1 gene. The DiMe Study Group. Childhood Diabetes in Finland. Hum Immunol 1996; 51: 41–48.

    Article  CAS  Google Scholar 

  35. Do H, Vasilescu A, Carpentier W, Meyer L, Diop G, Hirtzig T et al. Exhaustive genotyping of the interleukin-1 family genes and associations with AIDS progression in a French cohort. J Infect Dis 2006; 194: 1492–1504.

    Article  CAS  Google Scholar 

  36. Mahdaviani SA, Rezaei N, Moradi B, Dorkhosh S, Amirzargar AA, Movahedi M . Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma. J Clin Immunol 2009; 29: 57–62.

    Article  CAS  Google Scholar 

  37. Lang D, Knop J, Wesche H, Raffetseder U, Kurrle R, Boraschi D et al. The type II IL-1 receptor interacts with the IL-1 receptor accessory protein: a novel mechanism of regulation of IL-1 responsiveness. J Immunol 1998; 161: 6871–6877.

    CAS  PubMed  Google Scholar 

  38. Cavaillon JM, Fitting C, Caroff M, Haeffner-Cavaillon N . Dissociation of cell-associated interleukin-1 (IL-1) and IL-1 release induced by lipopolysaccharide and lipid A. Infect Immun 1989; 57: 791–797.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Wassarman DA, Sauer F . TAF(II)250: a transcription toolbox. J Cell Sci 2001; 114( Pt 16): 2895–902.

    CAS  PubMed  Google Scholar 

  40. Dikstein R, Ruppert S, Tjian R . TAFII250 is a bipartite protein kinase that phosphorylates the base transcription factor RAP74. Cell 1996; 84: 781–790.

    Article  CAS  Google Scholar 

  41. Mizzen CA, Yang XJ, Kokubo T, Brownell JE, Bannister AJ, Owen-Hughes T et al. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell 1996; 87: 1261–1270.

    Article  CAS  Google Scholar 

  42. Pham AD, Sauer F . Ubiquitin-activating/conjugating activity of TAFII250, a mediator of activation of gene expression in Drosophila. Science 2000; 289: 2357–2360.

    Article  CAS  Google Scholar 

  43. Lively TN, Ferguson HA, Galasinski SK, Seto AG, Goodrich JA . c-Jun binds the N terminus of human TAF(II)250 to derepress RNA polymerase II transcription in vitro. J Biol Chem 2001; 276: 25582–25588.

    Article  CAS  Google Scholar 

  44. Allende-Vega N, Saville MK, Meek DW . Transcription factor TAFII250 promotes Mdm2-dependent turnover of p53. Oncogene 2007; 26: 4234–4242.

    Article  CAS  Google Scholar 

  45. Kloet SL, Whiting JL, Gafken P, Ranish J, Wang EH . Phosphorylation-dependent regulation of cyclin D1 and cyclin A gene transcription by TFIID subunits TAF1 and TAF7. Mol Cell Biol 2012; 32: 3358–3369.

    Article  CAS  Google Scholar 

  46. Gordon S, Akopyan G, Garban H, Bonavida B . Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene 2006; 25: 1125–1142.

    Article  CAS  Google Scholar 

  47. Joo M, Wright JG, Hu NN, Sadikot RT, Park GY, Blackwell TS et al. Yin Yang 1 enhances cyclooxygenase-2 gene expression in macrophages. Am J Physiol Lung Cell Mol Physiol 2007; 292: L1219–L1226.

    Article  CAS  Google Scholar 

  48. Hess J, Angel P, Schorpp-Kistner M . AP-1 subunits: quarrel and harmony among siblings. J Cell Sci 2004; 117( Pt 25): 5965–5973.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Federal Target Program ‘Scientific and scientific-pedagogical personnel of innovative Russia’ for 2009–2013 (state contract no. 02.740.11.0707).

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  1. Laboratory of Molecular Immunology, Federal State Budgetary Institution ‘Research Institute of Clinical Immunology’, Russian Academy of Medical Sciences Siberian Branch, Novosibirsk, Russia

    FF Vasilyev, AN Silkov & SV Sennikov

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Correspondence to SV Sennikov.

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Vasilyev, F., Silkov, A. & Sennikov, S. Relationship between interleukin-1 type 1 and 2 receptor gene polymorphisms and the expression level of membrane-bound receptors. Cell Mol Immunol 12, 222–230 (2015). https://doi.org/10.1038/cmi.2014.43

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