1887

Abstract

The interaction between epithelial cells and micro-organisms is often a crucial initiating event in infectious diseases. Infection with , a Gram-negative anaerobe, is strongly associated with severe periodontal disease. This bacterium possesses an array of virulence factors, some of which can induce apoptosis. The tumour necrosis factor (TNF) receptor family is involved in the regulation of cellular homeostasis, cell surface molecules involved in phagocytosis, Fas ligand (L) expression and activation of the caspase cascade resulting in DNA fragmentation and cell blebbing. The current study examined the role of nuclear factor-B (NFB) in FasL-mediated apoptotic cell death in primary human gingival epithelial cells (HGEC) induced by heat-killed , probably through TLR signalling pathways. A marked up-regulation of TLR2 and Fas–FasL was detected in HGEC stimulated with . Activation of NFB by in HGEC was demonstrated by an NFB promoter luciferase assay as well as by phosphorylation of p65 as detected by Western blotting. Activation of cleaved caspase-3 and caspase-8 resulted in apoptotic cell death of HGEC. The survival proteins c-IAP-1/c-IAP-2 were decreased in HGEC exposed to . HGEC apoptosis induced by was inhibited by an anti-human FasL monoclonal antibody. Blockade of NFB by helenalin resulted in down-regulation of FasL whereas a caspase-8 inhibitor did not decrease FasL. Taken together, these studies show that can induce epithelial cell apoptosis through Fas–FasL up-regulation and activation of caspase-3 and caspase-8.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.28472-0
2006-03-01
2024-11-04
Loading full text...

Full text loading...

/deliver/fulltext/micro/152/3/797.html?itemId=/content/journal/micro/10.1099/mic.0.28472-0&mimeType=html&fmt=ahah

References

  1. Alikhani M, Alikhani Z, Graves D. T. 2005; FOXO1 functions as a master switch that regulates gene expression necessary for tumor necrosis factor-induced fibroblast apoptosis. J Biol Chem 280:12096–12102 [CrossRef]
    [Google Scholar]
  2. Asai Y, Ohyama Y, Gen K, Ogawa T. 2001; Bacterial fimbriae and their peptides activate human gingival epithelial cells through toll-like receptor 2. Infect Immun 69:7387–7395 [CrossRef]
    [Google Scholar]
  3. Asai Y, Jinno T, Ogawa T. 2003; Oral treponemes and their outer membrane extracts activate human gingival epithelial cells through toll-like receptor 2. Infect Immun 71:717–725 [CrossRef]
    [Google Scholar]
  4. Boldin M. P, Goncharov T. M, Goltsev Y. V, Wallach D. 1996; Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85:803–815 [CrossRef]
    [Google Scholar]
  5. Chen Y, Zychlinsky A. 1994; Apoptosis induced by bacterial pathogens. Microb Pathog 17:203–212 [CrossRef]
    [Google Scholar]
  6. Chinnaiyan A. M, O'Rourke K, Tewari M, Dixit V. M. 1995; FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81:505–512 [CrossRef]
    [Google Scholar]
  7. Chinnaiyan A. M, Tepper C. G, Seldin M. F, O'Rourke K, Kischkel F. C, Hellbardt S, Krammer P. H, Peter M. E, Dixit V. M. 1996; FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 271:4961–4965 [CrossRef]
    [Google Scholar]
  8. Farhana L, Dawson M. I, Fontana J. A. 2005; Apoptosis induction by a novel retinoid-related molecule requires nuclear factor- κ B activation. Cancer Res 65:4909–4917 [CrossRef]
    [Google Scholar]
  9. Gamonal J, Bascones A, Acevedo A, Blanco E, Silva A. 2001; Apoptosis in chronic adult periodontitis analyzed by in situ DNA breaks, electron microscopy, and immunohistochemistry. J Periodontol 72:517–525 [CrossRef]
    [Google Scholar]
  10. Gregoli P. A, Bondurant M. C. 1999; Function of caspases in regulating apoptosis caused by erythropoietin deprivation in erythroid progenitors. J Cell Physiol 178:133–143 [CrossRef]
    [Google Scholar]
  11. Hsu S.-C, Gavrilin M. A, Lee H.-H, Wu C.-C, Han S.-H, Lai M.-Z. 1999; NF- κ B-dependent Fas ligand expression. Eur J Immunol 29:2948–2956 [CrossRef]
    [Google Scholar]
  12. Kasumoto Y, Hirano H, Saitoh K. 10 other authors 2004; Human gingival epithelial cells produce chemotactic factors interleukin-8 and monocyte chemoattractant protein-1 after stimulation with Porphyromonas gingivalis via toll-like receptor 2. J Periodontol 75:370–379 [CrossRef]
    [Google Scholar]
  13. Koulouri O, Lappin D. F, Radvar M, Kinane D. F. 1999; Cell division, synthetic capacity and apoptosis in periodontal lesions analysed by in situ hybridisation and immunohistochemistry. J Clin Periodontol 26:552–559 [CrossRef]
    [Google Scholar]
  14. Kuroshima S, Sawa Y, Kawamoto T, Yamaoka Y, Notani K, Yoshida S, Inoue N. 2004; Expression of Toll-like receptors 2 and 4 on human intestinal lymphatic vessels. Microvasc Res 67:90–95 [CrossRef]
    [Google Scholar]
  15. Lash L. H, Hueni S. A, Putt D. A. 2001; Apoptosis, necrosis, and cell proliferation induced by S -(1,2-dichlorovinyl)-l-cysteine in primary cultures of human proximal tubular cells. Toxicol Appl Pharmacol 177:1–16 [CrossRef]
    [Google Scholar]
  16. Livak K. J, Schmittgen T. D. 2001; Analysis of relative gene expression data using real-time quantitative PCR and ΔΔCT method. Methods 25:402–408 [CrossRef]
    [Google Scholar]
  17. Lyss G, Knorre A, Schmidt T. J, Pahl H. L, Merfort I. 1998; The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF κ B by directly targeting p65. J Biol Chem 273:33508–33516 [CrossRef]
    [Google Scholar]
  18. McCloskey T. W, Chavan S, Lakshimi Tamma S. M, Pahwa S. 1998; Comparison of seven quantitative assays to assess lymphocytic cell death during HIV infection: measurement of induced apoptosis in anti-Fas treated Jurkat cells and spontaneous apoptosis in peripheral blood mononuclear cells from children infected with HIV. AIDS Res Hum Retroviruses 14:1413–1422 [CrossRef]
    [Google Scholar]
  19. Medema J. P, Scaffidi C, Kischkel F. C, Shevchenko A, Mann M, Krammer P. H, Peter M. E. 1997; FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J 16:2794–2804 [CrossRef]
    [Google Scholar]
  20. Nagata S. 1997; Apoptosis by death factor. Cell 88:355–365 [CrossRef]
    [Google Scholar]
  21. Nakhjiri S. F, Park Y, Yilmaz O, Chung W. O, Watanabe K, El-Sabeany A, Park K, Lamont R. J. 2001; Inhibition of epithelial cell apoptosis by Porphyromonas gingivalis . FEMS Microbiol Lett 2000145–149
    [Google Scholar]
  22. Offenbacher S. 1996; Periodontal diseases: pathogenesis. Ann Periodontol 1:821–827 [CrossRef]
    [Google Scholar]
  23. Roberts F. A, McCaffery K. A, Michalek S. M. 1997; Profile of cytokine mRNA expression in chronic adult periodontitis. J Dent Res 76:1833–1839 [CrossRef]
    [Google Scholar]
  24. Sandros J, Karlsson C, Lappin D. F, Madianos P. N, Kinane D. F, Papanou P. N. 2000; Cytokine responses of oral epithelial cells to Porphyromonas gingivalis infection. J Dent Res 79:1808–1814 [CrossRef]
    [Google Scholar]
  25. Savit E. D, Socransky S. S. 1984; Distribution of certain subgingival microbial species in selected periodontal conditions. J Periodont Res 19:111–123 [CrossRef]
    [Google Scholar]
  26. Slots J, Listgarten M. A. 1988; Bacteroides gingivalis , Bacteroides intermedius and Actinobacillus actinomycetemcomitans in human periodontal diseases. J Clin Periodontol 15:85–93 [CrossRef]
    [Google Scholar]
  27. Socransky S, Haffajee A. D. 1992; The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol 63:322–331 [CrossRef]
    [Google Scholar]
  28. Sugiyama A, Arakaki R, Ohnishi T, Arakaki N, Daikuhara Y, Takada H. 1996; Lipoteichoic acid and interleukin 1 stimulate synergistically production of hepatocyte growth factor (scatter factor) in human gingival fibroblasts in culture. Infect Immun 64:1426–1431
    [Google Scholar]
  29. Tonetti M. S, Imboden M. A, Gerber L, Lang N. P, Laissue J, Mueller C. 1994; Localized expression of mRNA for phagocyte-specific chemotactic cytokines in human periodontal infections. Infect Immun 62:4005–4014
    [Google Scholar]
  30. Tonetti M. S, Cortellini D, Lang N. P. 1998; In situ detection of apoptosis at sites of chronic bacterially induced inflammation in human gingiva. Infect Immun 66:5190–5195
    [Google Scholar]
  31. Uchida Y, Shiba H, Komatsuzawa H, Takemoto T, Sakata M, Fujita T, Kawaguchi H, Sugai M, Kurihara H. 2001; Expression of IL-1 β and IL-8 by human gingival epithelial cells in response to Actinobacillus actinomycetemcomitans . Cytokine 14:152–161 [CrossRef]
    [Google Scholar]
  32. Wang C.-Y, Mayo M. W, Korneluk R. G, Goeddel D. V, Baldwin A. S, Baldwin A. S Jr. 1998; NF- κ B antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683 [CrossRef]
    [Google Scholar]
  33. Wang D, Baldwin A. S, Baldwin A. S Jr. 1998; Activation of nuclear factor- κ B-dependent transcription by tumor necrosis factor- α is mediated through phosphorylation of RelA/p65 on serine 529. J Biol Chem 273:29411–29416 [CrossRef]
    [Google Scholar]
  34. Yilmaz , Jungas T, Verbeke P, Ojcius D. M. 2004; Activation of phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis . Infect Immun 72:3743–3751 [CrossRef]
    [Google Scholar]
  35. Yoshimura A, Kaneko T, Kato Y, Golenbock D. T, Hara Y. 2002; Lipopolysaccharides from periodontopathic bacteria Porphyromonas gingivalis and Capnocytophaga ochracea are antagonists for human Toll-like receptor 4. Infect Immun 70:218–225 [CrossRef]
    [Google Scholar]
  36. Yoshimura M. Y, Ukai T, Lien E, Espevik T, Hara Y. 2003; Immunohistochemical localization of Toll-like receptors 2 and 4 in gingival tissue from patients with periodontitis. Oral Microbiol Immunol 18:54–58 [CrossRef]
    [Google Scholar]
/content/journal/micro/10.1099/mic.0.28472-0
Loading
/content/journal/micro/10.1099/mic.0.28472-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error