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Inflammation Research

, 58:625 | Cite as

Epigenetics and periodontal disease: future perspectives

  • Ricardo Santiago Gomez
  • Walderez Ornelas Dutra
  • Paula Rocha MoreiraEmail author
Review

Abstract

Periodontitis is a multifactorial infection characterized by inflammation and destruction of tooth supporting tissues, as a result of the response of a susceptible host to bacterial challenge. Studies have demonstrated that epigenetic events are able to influence the production of cytokines, contributing to the development of inflammatory diseases. Epigenetic events act through the remodeling of chromatin and can selectively activate or inactivate genes, determining their expression. The epigenetic process, by inducing a change in cytokine profile, may subsequently influence the pathogenesis and determine the outcome of many infectious diseases. These findings may have relevance for inflammatory diseases in which the expression of cytokines is unregulated. The purpose of this review is to show evidence that supports the hypothesis that epigenetic alterations, such as hyper and hypomethylation, of cytokine genes, could help to understand the mechanisms related to periodontal disease activity. Therefore, epigenetics may have future impact on diagnosis and/or therapeutics of periodontal disease.

Keywords

Epigenetic Methylation Periodontitis Inflammation Cytokines 

Notes

Acknowledgments

RS Gomez, WO Dutra and PR Moreira are research fellows of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

References

  1. 1.
    Kinane DF, Hart TC. Genes and gene polymorphisms associated with periodontal disease. Crit Rev Oral Biol Med. 2003;14(6):430–49.PubMedCrossRefGoogle Scholar
  2. 2.
    Shapira L, Wilensky A, Kinane DF. Effect of genetic variability on the inflammatory response to periodontal infection. J Clin Periodontol. 2005;32:72–86.PubMedCrossRefGoogle Scholar
  3. 3.
    Bodet C, Chandad F, Grenier D. Porphyromonas gingivalis-induced inflammatory mediator profile in an ex vivo human whole blood model. Clin Exp Immunol. 2006;143:50–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Borrell LN, Papapanou PN. Analytical epidemiology of periodontitis. J Clin Periodontol. 2005;32:132–58.PubMedCrossRefGoogle Scholar
  5. 5.
    Takashiba S, Naruishi K. Gene polymorphisms in periodontal health and disease. Periodontol. 2006;2000(40):94–106.CrossRefGoogle Scholar
  6. 6.
    American Academy of Periodontology. Epidemiology of periodontal disease. J Periodontol. 2005;76:1406–19.CrossRefGoogle Scholar
  7. 7.
    Adcock IA, Tsaprouni L, Bhavsar P, Ito K. Epigenetic regulation of airway inflammation. Curr Opin Immunol. 2007;19:694–700.PubMedCrossRefGoogle Scholar
  8. 8.
    Narlikar GJ, Fan HY, Kingston RE. Cooperation between complexes that regulate chromatin structure and transcription. Cell. 2002;108:475–87.PubMedCrossRefGoogle Scholar
  9. 9.
    Shaw R. The epigenetics of oral cancer. Int J Oral Maxillofac Surg. 2006;35:101–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Sanders VM. Epigenetic regulation of Th1 and Th2 cell development. Brain Behav Immun. 2006;20:317–24.PubMedCrossRefGoogle Scholar
  11. 11.
    Bäckdahl L, Bushell A, Beck S. Inflammatory signalling as mediator of epigenetic modulation in tissue-specific chronic inflammation. Int J Biochem Cell Biol. 2009;41(1):176–84.PubMedCrossRefGoogle Scholar
  12. 12.
    Gazzar ME, Yoza BK, Hu J, Cousart SL, McCall CE. Epigenetic silencing of tumor necrosis α during endotoxin tolerance. J Biol Chem. 2007;282:26857–64.PubMedCrossRefGoogle Scholar
  13. 13.
    Fitzpatrick DR, Wilson CB. Methylation and demethylation in the regulation of genes, cells, and responses in the immune system. Clin Immunol. 2003;109:37–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Johnson IT, Belshaw NJ. Environment, diet and CpG island methylation: epigenetic signals in gastrointestinal neoplasia. Food Chem Toxicol. 2008;46:1346–59.PubMedCrossRefGoogle Scholar
  15. 15.
    Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998;19:187–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998;393:386–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429(6990):457–63.PubMedCrossRefGoogle Scholar
  18. 18.
    Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet. 2000;24(1):88–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Sánchez-Pernaute O, Ospelt C, Neidhart M, Gay S. Epigenetic clues to rheumatoid arthritis. J Autoimmun. 2008;30:12–20.PubMedCrossRefGoogle Scholar
  20. 20.
    White GP, Watt PM, Holt BJ, Holt PG. Differential patterns of methylation of the IFN-gamma promoter at CpG and non-CpG sites underlie differences in IFN-gamma gene expression between human neonatal and adult CD45RO-T cells. J Immunol. 2002;168:2820–7.PubMedGoogle Scholar
  21. 21.
    Armenante F, Merola M, Furia A, Palmieri M. Repression of the IL-6 gene is associated with hypermethylation. Biochem Biophys Res Commun. 1999;258:644–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Sullivan KE, Reddy ABM, Dietzmann K, Suriano AR, Kocieda VP, Stewart M, et al. Epigenetic regulation of tumor necrosis factor alpha. Mol Cell Biol. 2007;27:5147–60.PubMedCrossRefGoogle Scholar
  23. 23.
    Hmadcha A, Bedoya FJ, Sobrino F, Pintado E. Methylation-dependent gene silencing induced by interleukin 1b via nitric oxide production. J Exp Med. 1999;190:1595–603.PubMedCrossRefGoogle Scholar
  24. 24.
    Hodge DR, Xiao W, Clausen PA, Heidecker G, Szyf M, Farrar WL. Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erytroleukemia cells. J Biol Chem. 2001;276:39508–11.PubMedCrossRefGoogle Scholar
  25. 25.
    Wehbe H, Henson R, Meng F, Mize-Berge J, Patel T. Interleukin-6 contributes to growth in cholangiocarcinoma cells by aberrant promoter methylation and gene expression. Cancer Res. 2006;66:10517–24.PubMedCrossRefGoogle Scholar
  26. 26.
    Reiner SL. Epigenetic control in the immune response. Hum Mol Genet. 2005;14:R41–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Issa J-P. Age-related epigenetic changes and the immune system. Clin Immunol. 2003;109:103–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Kwon N-H, Kim J-S, Le J-Y, Oh M-J, Choi D-C. DNA methylation and the expression of IL-4 and IFN-g promoter genes in patients with bronchial asthma. J Clin Immunol. 2008;28:139–46.PubMedCrossRefGoogle Scholar
  29. 29.
    Mi X, Zeng F. Hypomethylation of interleukin-4 and 6 promoters in T cells from systemic lupus erythematosus. Acta Pharmacol Sin. 2008;29:105–12.PubMedCrossRefGoogle Scholar
  30. 30.
    Fu LH, Cong B, Zhen YF, Li SJ, Ma CL, Ni ZY, et al. Methylation status of the IL-10 gene promoter in the peripheral blood mononuclear cells of rheumatoid arthritis patients. Yi Chuan. 2007;29:1357–61. abstract.PubMedGoogle Scholar
  31. 31.
    Wilson AG. Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J Periodontol. 2008;79:1514–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Moreira PR, Lima PMA, Sathler KOB, Imanishi SA, Costa JE, Gomes RS, et al. Interleukin-6 expression and gene polymorphism are associated with severity of periodontal disease in a sample of Brazilian individuals. Clin Exp Immunol. 2007;148:119–26.PubMedGoogle Scholar
  33. 33.
    Offenbacher S, Barros SP, Beck JD. Rethinking periodontal inflammation. J Periodontol. 2008;79:1577–84.PubMedCrossRefGoogle Scholar
  34. 34.
    Stenvinkel P, Karimi M, Johansson S, Axelsson J, Suliman M, Lindholm B, et al. Impact of inflammation on epigenetic DNA methylation: a novel risk factor for cardiovascular disease? J Intern Med. 2007;261:488–99.PubMedCrossRefGoogle Scholar
  35. 35.
    Hodge DR, Peng B, Cherry JC, Hurt EM, Fox SD, Kelley JA, et al. Interleukin 6 supports the maintenance of p53 tumor suppressor gene promotor methylation. Cancer Res. 2005;65:4673–82.PubMedCrossRefGoogle Scholar
  36. 36.
    Bobetsis YA, Barros SP, Lin DM, Weidman JR, Dolinoy DC, Jirtle RL, et al. Bacterial infection promotes DNA hypermethylation. J Dent Res. 2007;86:169–74.PubMedCrossRefGoogle Scholar
  37. 37.
    Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102:10604–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Vaissière T, Sawan C, Herceg Z. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res. 2008;659:40–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Hillemacher T, Frieling H, Moskau S, Muschler MA, Semmler A, Kornhuber J, et al. Global DNA methylation is influenced by smoking behaviour. Eur Neuropsychopharmacol. 2008;18:295–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Kikuchi S, Yamada D, Fukami T, Maruyama T, Ito A, Asamura H, et al. Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary non-small cell lung carcinoma. Cancer. 2006;106:1751–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Ohi T, Uehara Y, Takatsu M, Watanabe M, Ono T. Hypermethylation of CpG in the promoter of the COL1A1 gene in the aged periodontal ligament. J Dent Res. 2006;85:245–50.PubMedCrossRefGoogle Scholar
  42. 42.
    Wu H, Lippmann JE, Oza JP, Zeng M, Fives-Taylor P, Reich NO. Inactivation of DNA adenine methyltransferase alters virulence factors in Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol. 2006;21:238–44.PubMedCrossRefGoogle Scholar
  43. 43.
    Bonilla-Henao V, Martinez R, Sobrino F, Pintado E. Different signaling pathways inhibit DNA methylation activity and up-regulate IFN-γ in human lymphocytes. J Leukoc Biol. 2005;78:1339–46.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Ricardo Santiago Gomez
    • 1
  • Walderez Ornelas Dutra
    • 2
  • Paula Rocha Moreira
    • 1
    • 3
    Email author
  1. 1.Laboratory of Molecular Biology, Department of Oral Surgery and Pathology, School of DentistryUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Laboratory of Cell–Cell Interactions, Department of Morphology, Institute of Biological SciencesUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Laboratório de Biologia Molecular, Faculdade de OdontologiaUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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