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. 1997 Aug;65(8):3199–3202. doi: 10.1128/iai.65.8.3199-3202.1997

Activation of the interleukin-1beta precursor by Treponema denticola: a potential role in chronic inflammatory periodontal diseases.

A Beauséjour 1, N Deslauriers 1, D Grenier 1
PMCID: PMC175452  PMID: 9234775

Abstract

There are several indications suggesting that interleukin-1beta (IL-1beta) may play an important role in inflammatory periodontal diseases. We hypothesized that periodontal sites would represent a unique combination of both cellular sources of IL-1beta precursor (pro-IL-1beta) and microbial proteases and proposed that Treponema denticola, a suspected periodontal pathogen, would play a critical role in the inflammatory nature of adult chronic periodontitis by activating pro-IL-1beta. The aim of this study was thus to demonstrate the proteolytic cleavage and activation of the inactive precursor pro-IL-1beta by T. denticola. After incubation of bacterial cells with recombinant pro-IL-1beta, proteolytic cleavage was monitored by Western immunoblotting, and the biological activity of the digestion products was tested in a bioassay. We report here that T. denticola can cleave pro-IL-1beta to yield two fragments with molecular masses of 18 and 19 kDa. Cleavage products showed a dose-dependent biological activity in the thymocyte proliferation bioassay, and this activity was inhibited by anti-IL-1beta neutralizing antibodies. These results suggest that T. denticola may have a proinflammatory role in periodontal diseases.

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Selected References

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  1. Auron P. E., Warner S. J., Webb A. C., Cannon J. G., Bernheim H. A., McAdam K. J., Rosenwasser L. J., LoPreste G., Mucci S. F., Dinarello C. A. Studies on the molecular nature of human interleukin 1. J Immunol. 1987 Mar 1;138(5):1447–1456. [PubMed] [Google Scholar]
  2. Birkedal-Hansen H. Role of cytokines and inflammatory mediators in tissue destruction. J Periodontal Res. 1993 Nov;28(6 Pt 2):500–510. doi: 10.1111/j.1600-0765.1993.tb02113.x. [DOI] [PubMed] [Google Scholar]
  3. Black R. A., Kronheim S. R., Cantrell M., Deeley M. C., March C. J., Prickett K. S., Wignall J., Conlon P. J., Cosman D., Hopp T. P. Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor. J Biol Chem. 1988 Jul 5;263(19):9437–9442. [PubMed] [Google Scholar]
  4. Dinarello C. A. The biological properties of interleukin-1. Eur Cytokine Netw. 1994 Nov-Dec;5(6):517–531. [PubMed] [Google Scholar]
  5. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Grenier D. Degradation of host protease inhibitors and activation of plasminogen by proteolytic enzymes from Porphyromonas gingivalis and Treponema denticola. Microbiology. 1996 Apr;142(Pt 4):955–961. doi: 10.1099/00221287-142-4-955. [DOI] [PubMed] [Google Scholar]
  7. Grenier D., Mayrand D. Adult periodontitis: an ecological perspective of mixed infections. Trends Microbiol. 1995 Apr;3(4):148–148. doi: 10.1016/s0966-842x(00)88904-0. [DOI] [PubMed] [Google Scholar]
  8. Haffajee A. D., Socransky S. S. Microbial etiological agents of destructive periodontal diseases. Periodontol 2000. 1994 Jun;5:78–111. doi: 10.1111/j.1600-0757.1994.tb00020.x. [DOI] [PubMed] [Google Scholar]
  9. Hazuda D. J., Lee J. C., Young P. R. The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1 alpha and interleukin 1 beta. J Biol Chem. 1988 Jun 15;263(17):8473–8479. [PubMed] [Google Scholar]
  10. Hazuda D. J., Strickler J., Kueppers F., Simon P. L., Young P. R. Processing of precursor interleukin 1 beta and inflammatory disease. J Biol Chem. 1990 Apr 15;265(11):6318–6322. [PubMed] [Google Scholar]
  11. Hou L. T., Liu C. M., Rossomando E. F. Crevicular interleukin-1 beta in moderate and severe periodontitis patients and the effect of phase I periodontal treatment. J Clin Periodontol. 1995 Feb;22(2):162–167. doi: 10.1111/j.1600-051x.1995.tb00128.x. [DOI] [PubMed] [Google Scholar]
  12. Jandinski J. J., Stashenko P., Feder L. S., Leung C. C., Peros W. J., Rynar J. E., Deasy M. J. Localization of interleukin-1 beta in human periodontal tissue. J Periodontol. 1991 Jan;62(1):36–43. doi: 10.1902/jop.1991.62.1.36. [DOI] [PubMed] [Google Scholar]
  13. Kapur V., Majesky M. W., Li L. L., Black R. A., Musser J. M. Cleavage of interleukin 1 beta (IL-1 beta) precursor to produce active IL-1 beta by a conserved extracellular cysteine protease from Streptococcus pyogenes. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7676–7680. doi: 10.1073/pnas.90.16.7676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kostura M. J., Tocci M. J., Limjuco G., Chin J., Cameron P., Hillman A. G., Chartrain N. A., Schmidt J. A. Identification of a monocyte specific pre-interleukin 1 beta convertase activity. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5227–5231. doi: 10.1073/pnas.86.14.5227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Leschine S. B., Canale-Parola E. Rifampin as a selective agent for isolation of oral spirochetes. J Clin Microbiol. 1980 Dec;12(6):792–795. doi: 10.1128/jcm.12.6.792-795.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Loesche W. J. The role of spirochetes in periodontal disease. Adv Dent Res. 1988 Nov;2(2):275–283. doi: 10.1177/08959374880020021201. [DOI] [PubMed] [Google Scholar]
  18. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  19. Matsushima K., Taguchi M., Kovacs E. J., Young H. A., Oppenheim J. J. Intracellular localization of human monocyte associated interleukin 1 (IL 1) activity and release of biologically active IL 1 from monocytes by trypsin and plasmin. J Immunol. 1986 Apr 15;136(8):2883–2891. [PubMed] [Google Scholar]
  20. Mikx F. H., Maltha J. C., van Campen G. J. Spirochetes in early lesions of necrotizing ulcerative gingivitis experimentally induced in beagles. Oral Microbiol Immunol. 1990 Apr;5(2):86–89. doi: 10.1111/j.1399-302x.1990.tb00233.x. [DOI] [PubMed] [Google Scholar]
  21. Mizutani H., Black R., Kupper T. S. Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta. Different strategies of IL-1 production and processing in monocytes and keratinocytes. J Clin Invest. 1991 Mar;87(3):1066–1071. doi: 10.1172/JCI115067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mizutani H., Schechter N., Lazarus G., Black R. A., Kupper T. S. Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase. J Exp Med. 1991 Oct 1;174(4):821–825. doi: 10.1084/jem.174.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moore W. E., Holdeman L. V., Smibert R. M., Hash D. E., Burmeister J. A., Ranney R. R. Bacteriology of severe periodontitis in young adult humans. Infect Immun. 1982 Dec;38(3):1137–1148. doi: 10.1128/iai.38.3.1137-1148.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mosley B., Dower S. K., Gillis S., Cosman D. Determination of the minimum polypeptide lengths of the functionally active sites of human interleukins 1 alpha and 1 beta. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4572–4576. doi: 10.1073/pnas.84.13.4572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  26. Mäkinen K. K., Chen C. Y., Mäkinen P. L. Proline iminopeptidase from the outer cell envelope of the human oral spirochete Treponema denticola ATCC 35405. Infect Immun. 1996 Mar;64(3):702–708. doi: 10.1128/iai.64.3.702-708.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mäkinen K. K., Mäkinen P. L. The peptidolytic capacity of the spirochete system. Med Microbiol Immunol. 1996 May;185(1):1–10. doi: 10.1007/s004300050008. [DOI] [PubMed] [Google Scholar]
  28. Ohshima M., Otsuka K., Suzuki K. Interleukin-1 beta stimulates collagenase production by cultured human periodontal ligament fibroblasts. J Periodontal Res. 1994 Nov;29(6):421–429. doi: 10.1111/j.1600-0765.1994.tb01244.x. [DOI] [PubMed] [Google Scholar]
  29. Ohta K., Makinen K. K., Loesche W. J. Purification and characterization of an enzyme produced by Treponema denticola capable of hydrolyzing synthetic trypsin substrates. Infect Immun. 1986 Jul;53(1):213–220. doi: 10.1128/iai.53.1.213-220.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Preiss D. S., Meyle J. Interleukin-1 beta concentration of gingival crevicular fluid. J Periodontol. 1994 May;65(5):423–428. doi: 10.1902/jop.1994.65.5.423. [DOI] [PubMed] [Google Scholar]
  31. Rosen G., Naor R., Kutner S., Sela M. N. Characterization of fibrinolytic activities of Treponema denticola. Infect Immun. 1994 May;62(5):1749–1754. doi: 10.1128/iai.62.5.1749-1754.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Seymour G. J., Gemmell E., Reinhardt R. A., Eastcott J., Taubman M. A. Immunopathogenesis of chronic inflammatory periodontal disease: cellular and molecular mechanisms. J Periodontal Res. 1993 Nov;28(6 Pt 2):478–486. doi: 10.1111/j.1600-0765.1993.tb02108.x. [DOI] [PubMed] [Google Scholar]
  33. Tatakis D. N. Interleukin-1 and bone metabolism: a review. J Periodontol. 1993 May;64(5 Suppl):416–431. [PubMed] [Google Scholar]
  34. Thornberry N. A. Interleukin-1 beta converting enzyme. Methods Enzymol. 1994;244:615–631. doi: 10.1016/0076-6879(94)44045-x. [DOI] [PubMed] [Google Scholar]
  35. Uitto V. J., Grenier D., Chan E. C., McBride B. C. Isolation of a chymotrypsinlike enzyme from Treponema denticola. Infect Immun. 1988 Oct;56(10):2717–2722. doi: 10.1128/iai.56.10.2717-2722.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Uitto V. J., Pan Y. M., Leung W. K., Larjava H., Ellen R. P., Finlay B. B., McBride B. C. Cytopathic effects of Treponema denticola chymotrypsin-like proteinase on migrating and stratified epithelial cells. Infect Immun. 1995 Sep;63(9):3401–3410. doi: 10.1128/iai.63.9.3401-3410.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williams R. C. Periodontal disease. N Engl J Med. 1990 Feb 8;322(6):373–382. doi: 10.1056/NEJM199002083220606. [DOI] [PubMed] [Google Scholar]

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