Skip to main content

Advertisement

Log in

Porphyromonas gingivalis Induces RANKL in T-cells

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Porphyromonas gingivalis is an oral pathogen highly implicated in chronic periodontitis, a disease characterized by inflammatory destruction of the tooth-supporting alveolar bone and eventually, tooth loss. T-cell innate immune responses are actively involved in this pathological process. Receptor activator of NF-κB Ligand (RANKL) is a cytokine that stimulates bone resorption, while its soluble decoy receptor osteoprotegerin (OPG) blocks its action. This study aimed to investigate in Jurkat T-cells the effects of P. gingivalis on the RANKL-OPG system and the major inflammatory mediator of bone resorption prostaglandin E2 (PGE2). P. gingivalis caused concentration-dependent up-regulation of RANKL gene expression and protein production, assessed by quantitative PCR and ELISA, respectively. PGE2 production was also enhanced. However, OPG was not detected. In conclusion, P. gingivalis induces RANKL and PGE2 in T-cells, potentially favoring bone resorption. These T-cell responses to P. gingivalis may contribute to the pathogenesis of inflammatory alveolar bone destruction occurring in chronic periodontitis.

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

Similar content being viewed by others

References

  1. Slots, J., L. Bragd, M. Wikstrom, and G. Dahlen. 1986. The occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius in destructive periodontal disease in adults. J Clin Periodontol 13: 570–577.

    Article  PubMed  CAS  Google Scholar 

  2. Genco, R.J., A.W. Ho, J. Kopman, S.G. Grossi, R.G. Dunford, and L.A. Tedesco. 1998. Models to evaluate the role of stress in periodontal disease. Ann Periodontol 3: 288–302.

    Article  PubMed  CAS  Google Scholar 

  3. Dixon, D.R., and R.P. Darveau. 2005. Lipopolysaccharide heterogeneity: innate host responses to bacterial modification of lipid a structure. J Dent Res 84: 584–595.

    Article  PubMed  CAS  Google Scholar 

  4. Curtis, M.A., J. Aduse-Opoku, and M. Rangarajan. 2001. Cysteine proteases of Porphyromonas gingivalis. Crit Rev Oral Biol Med 12: 192–216.

    Article  PubMed  CAS  Google Scholar 

  5. Bostanci, N., R.P. Allaker, G.N. Belibasakis, M. Rangarajan, M.A. Curtis, F.J. Hughes, and I.J. McKay. 2007. Porphyromonas gingivalis antagonises Campylobacter rectus induced cytokine production by human monocytes. Cytokine 39: 147–156.

    Article  PubMed  CAS  Google Scholar 

  6. Rautemaa, R., A. Jarvensivu, K. Kari, J. Wahlgren, A. DeCarlo, M. Richardson, and T. Sorsa. 2004. Intracellular localization of Porphyromonas gingivalis thiol proteinase in periodontal tissues of chronic periodontitis patients. Oral Dis 10: 298–305.

    Article  PubMed  CAS  Google Scholar 

  7. Page, R.C., and H.E. Schroeder. 1976. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest 34: 235–249.

    PubMed  CAS  Google Scholar 

  8. Gemmell, E., K. Yamazaki, and G.J. Seymour. 2007. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontol 2000 43: 14–40.

    Article  PubMed  Google Scholar 

  9. Taubman, M.A., and T. Kawai. 2001. Involvement of T-lymphocytes in periodontal disease and in direct and indirect induction of bone resorption. Crit Rev Oral Biol Med 12: 125–135.

    Article  PubMed  CAS  Google Scholar 

  10. Gaffen, S.L., and G. Hajishengallis. 2008. A new inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res 87: 817–828.

    Article  PubMed  CAS  Google Scholar 

  11. Sato, K., A. Suematsu, K. Okamoto, A. Yamaguchi, Y. Morishita, Y. Kadono, S. Tanaka, T. Kodama, S. Akira, Y. Iwakura, D.J. Cua, and H. Takayanagi. 2006. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203: 2673–2682.

    Article  PubMed  CAS  Google Scholar 

  12. Lerner, U.H. 2006. Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis. J Dent Res 85: 596–607.

    Article  PubMed  CAS  Google Scholar 

  13. Kong, Y.Y., W.J. Boyle, and J.M. Penninger. 1999. Osteoprotegerin ligand: a common link between osteoclastogenesis, lymph node formation and lymphocyte development. Immunol Cell Biol 77: 188–193.

    Article  PubMed  CAS  Google Scholar 

  14. Udagawa, N., N. Takahashi, E. Jimi, K. Matsuzaki, T. Tsurukai, K. Itoh, N. Nakagawa, H. Yasuda, M. Goto, E. Tsuda, K. Higashio, M.T. Gillespie, T.J. Martin, and T. Suda. 1999. Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand. Bone 25: 517–523.

    Article  PubMed  CAS  Google Scholar 

  15. Simonet, W.S., D.L. Lacey, C.R. Dunstan, M. Kelley, M.S. Chang, R. Luthy, H.Q. Nguyen, S. Wooden, L. Bennett, T. Boone, G. Shimamoto, M. DeRose, R. Elliott, A. Colombero, H.L. Tan, G. Trail, J. Sullivan, E. Davy, N. Bucay, L. Renshaw-Gegg, T.M. Hughes, D. Hill, W. Pattison, P. Campbell, S. Sander, G. Van, J. Tarpley, P. Derby, R. Lee, and W.J. Boyle. 1997. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89: 309–319.

    Article  PubMed  CAS  Google Scholar 

  16. Bostanci, N., T. Ilgenli, G. Emingil, B. Afacan, B. Han, H. Toz, G. Atilla, F.J. Hughes, and G.N. Belibasakis. 2007. Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. J Clin Periodontol 34: 370–376.

    Article  PubMed  CAS  Google Scholar 

  17. Bostanci, N., T. Ilgenli, G. Emingil, B. Afacan, B. Han, H. Toz, A. Berdeli, G. Atilla, I.J. McKay, F.J. Hughes, and G.N. Belibasakis. 2007. Differential expression of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin mRNA in periodontal diseases. J Periodontal Res 42: 287–293.

    Article  PubMed  CAS  Google Scholar 

  18. Belibasakis, G.N., N. Bostanci, A. Hashim, A. Johansson, J. Aduse-Opoku, M.A. Curtis, and F.J. Hughes. 2007. Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains. Microb Pathog 43: 46–53.

    Article  PubMed  CAS  Google Scholar 

  19. Reddi, D., N. Bostanci, A. Hashim, J. Aduse-Opoku, M.A. Curtis, F.J. Hughes, and G.N. Belibasakis. 2008. Porphyromonas gingivalis regulates the RANKL-OPG system in bone marrow stromal cells. Microbes Infect 10: 1459–1468.

    Article  PubMed  CAS  Google Scholar 

  20. Choi, B.K., S.Y. Moon, J.H. Cha, K.W. Kim, and Y.J. Yoo. 2005. Prostaglandin E(2) is a main mediator in receptor activator of nuclear factor-kappaB ligand-dependent osteoclastogenesis induced by Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii. J Periodontol 76: 813–820.

    Article  PubMed  CAS  Google Scholar 

  21. Okahashi, N., H. Inaba, I. Nakagawa, T. Yamamura, M. Kuboniwa, K. Nakayama, S. Hamada, and A. Amano. 2004. Porphyromonas gingivalis induces receptor activator of NF-kappaB ligand expression in osteoblasts through the activator protein 1 pathway. Infect Immun 72: 1706–1714.

    Article  PubMed  CAS  Google Scholar 

  22. Gemmell, E., P.S. Bird, J.J. Bowman, L. Xu, B. Polak, L.J. Walsh, and G.J. Seymour. 1997. Immunohistological study of lesions induced by Porphyromonas gingivalis in a murine model. Oral Microbiol Immunol 12: 288–297.

    Article  PubMed  CAS  Google Scholar 

  23. Gemmell, E., T.A. Winning, P.S. Bird, and G.J. Seymour. 1998. Cytokine profiles of lesional and splenic T cells in Porphyromonas gingivalis infection in a murine model. J Periodontol 69: 1131–1138.

    PubMed  CAS  Google Scholar 

  24. Baker, P.J., J. Garneau, L. Howe, and D.C. Roopenian. 2001. T-cell contributions to alveolar bone loss in response to oral infection with Porphyromonas gingivalis. Acta Odontol Scand 59: 222–225.

    Article  PubMed  CAS  Google Scholar 

  25. Stashenko, P., R.B. Goncalves, B. Lipkin, A. Ficarelli, H. Sasaki, and A. Campos-Neto. 2007. Th1 immune response promotes severe bone resorption caused by Porphyromonas gingivalis. Am J Pathol 170: 203–213.

    Article  PubMed  CAS  Google Scholar 

  26. Bostanci, N., D. Reddi, M. Rangarajan, M.A. Curtis, and G.N. Belibasakis. 2009. Porphyromonas gingivalis stimulates TACE production by T cells. Oral Microbiol Immunol 24: 146–151.

    Article  PubMed  CAS  Google Scholar 

  27. Lum, L., B.R. Wong, R. Josien, J.D. Becherer, H. Erdjument-Bromage, J. Schlondorff, P. Tempst, Y. Choi, and C.P. Blobel. 1999. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. J Biol Chem 274: 13613–13618.

    Article  PubMed  CAS  Google Scholar 

  28. Belibasakis, G.N., M. Brage, T. Lagergard, and A. Johansson. 2008. Cytolethal distending toxin upregulates RANKL expression in Jurkat T-cells. APMIS 116: 499–506.

    Article  PubMed  CAS  Google Scholar 

  29. Chakravarti, A., A.A. Marceau, L. Flamand, and P.E. Poubelle. 2008. Normal human primary CD4+ T lymphocytes synthesize and release functional osteoprotegerin in vitro. Lab Invest 88: 171–184.

    Article  PubMed  CAS  Google Scholar 

  30. Raisz, L.G. 1990. The role of prostaglandins in the local regulation of bone metabolism. Prog Clin Biol Res 332: 195–203.

    PubMed  CAS  Google Scholar 

  31. Offenbacher, S., B.M. Odle, and T.E. Van Dyke. 1986. The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss. J Periodontal Res 21: 101–112.

    Article  PubMed  CAS  Google Scholar 

  32. Noguchi, K., and I. Ishikawa. 2007. The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease. Periodontol 2000 43: 85–101.

    Article  PubMed  Google Scholar 

  33. Schafer, D., M. Schmid, U.C. Gode, and H.W. Baenkler. 1999. Dynamics of eicosanoids in peripheral blood cells during bronchial provocation in aspirin-intolerant asthmatics. Eur Respir J 13: 638–646.

    Article  PubMed  CAS  Google Scholar 

  34. Futagami, S., T. Hiratsuka, A. Tatsuguchi, K. Suzuki, M. Kusunoki, Y. Shinji, K. Shinoki, T. Iizumi, T. Akamatsu, H. Nishigaki, K. Wada, K. Miyake, K. Gudis, T. Tsukui, and C. Sakamoto. 2003. Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori-stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells. Gut 52: 1257–1264.

    Article  PubMed  CAS  Google Scholar 

  35. Burgermeister, E., J. Endl, and W.V. Scheuer. 2003. Activation of cytosolic phospholipase A2 in human T-lymphocytes involves inhibitor-kappaB and mitogen-activated protein kinases. Eur J Pharmacol 466: 169–180.

    Article  PubMed  CAS  Google Scholar 

  36. Steffen, M.J., S.C. Holt, and J.L. Ebersole. 2000. Porphyromonas gingivalis induction of mediator and cytokine secretion by human gingival fibroblasts. Oral Microbiol Immunol 15: 172–180.

    Article  PubMed  CAS  Google Scholar 

  37. Bodet, C., F. Chandad, and D. Grenier. 2006. Inflammatory responses of a macrophage/epithelial cell co-culture model to mono and mixed infections with Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Microbes Infect 8: 27–35.

    Article  PubMed  CAS  Google Scholar 

  38. Bodet, C., F. Chandad, and D. Grenier. 2006. Porphyromonas gingivalis-induced inflammatory mediator profile in an ex vivo human whole blood model. Clin Exp Immunol 143: 50–57.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the authors’ institutes. The authors would like to thank Prof. Michael Curtis (The Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry) for providing the P. gingivalis strain.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Georgios N. Belibasakis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Belibasakis, G.N., Reddi, D. & Bostanci, N. Porphyromonas gingivalis Induces RANKL in T-cells. Inflammation 34, 133–138 (2011). https://doi.org/10.1007/s10753-010-9216-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-010-9216-1

KEY WORDS

Navigation