Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Free

Abstract

Cysteine proteinases from , or gingipains, are considered to be key virulence factors of the bacterium in relation to periodontal diseases. Incubation of human oral epithelial cells with lysine-specific gingipain (Kgp) and high-molecular-mass arginine-specific gingipain (HRgpA) resulted in a decrease in the production of interleukin (IL)-8, but not in the production of other pro-inflammatory cytokines. In contrast, arginine-specific gingipain 2 (RgpB) increased IL-8 production. RNA interference assays demonstrated that Kgp- and HRgpA-mediated downregulation and RgpB-mediated upregulation occurred through protease-activated receptor (PAR)-1 and PAR-2 signalling. Although the RgpB-mediated upregulation of IL-8 production occurred through nuclear factor-kappa B (NF-B), the Kgp- and HRgpA-mediated downregulation was not negated in NF-B-silenced cells. Both the haemagglutinin and the enzymic domains are required for Kgp and HRgpA to downregulate the production of IL-8 in human oral epithelial cells, and the two domains are thought to co-exist. These results suggest that gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.47679-0
2008-04-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/57/4/500.html?itemId=/content/journal/jmm/10.1099/jmm.0.47679-0&mimeType=html&fmt=ahah

References

  1. Acheson D. W. K., Luccioli S. 2004; Microbial–gut interactions in health and disease. Mucosal immune responses. Best Pract Res Clin Gastroenterol 18:387–404 [CrossRef]
    [Google Scholar]
  2. Chen Z., Potempa J., Polanowski A., Wikstrom M., Travis J. 1992; Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis . J Biol Chem 267:18896–18901
    [Google Scholar]
  3. Coughlin S. R. 2000; Thrombin signalling and protease-activated receptors. Nature 407:258–264 [CrossRef]
    [Google Scholar]
  4. Déry O., Corvera C. U., Steinhoff M., Bunnett N. W. 1998; Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am J Physiol 274:C1429–C1452
    [Google Scholar]
  5. Dixon D. R., Bainbridge B. W., Darveau R. P. 2004; Modulation of the innate immune response within the periodontium. Periodontol 2000; 35:53–74 [CrossRef]
    [Google Scholar]
  6. Holt S. C., Bramanti T. E. 1991; Factors in virulence expression and their role in periodontal disease pathogenesis. Crit Rev Oral Biol Med 2:177–281
    [Google Scholar]
  7. Kadowaki T., Yoneda M., Okamoto K., Maeda K., Yamamoto K. 1994; Purification and characterization of a novel arginine-specific cysteine proteinase (argingipain) involved in the pathogenesis of periodontal disease from the culture supernatant of Porphyromonas gingivalis . J Biol Chem 269:21371–21378
    [Google Scholar]
  8. Liu R. K., Cao C. F., Meng H. X., Gao Y. 2001; Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis. J Periodontol 72:1545–1553 [CrossRef]
    [Google Scholar]
  9. Lourbakos A., Chinni C., Thompson P., Potempa J., Travis J., Mackie E. J., Pike R. N. 1998; Cleavage and activation of proteinase-activated receptor-2 on human neutrophils by gingipain-R from Porphyromonas gingivalis . FEBS Lett 435:45–48 [CrossRef]
    [Google Scholar]
  10. Lourbakos A., Potempa J., Travis J., D'Andrea M. R., Andrade-Gordon P., Santulli R., Mackie E. J., Pike R. N. 2001a; Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion. Infect Immun 69:5121–5130 [CrossRef]
    [Google Scholar]
  11. Lourbakos A., Yuan Y., Jenkins A. L., Travis J., Andrade-Gordon P., Santulli R., Potempa J., Pike R. N. 2001b; Activation of protease-activated receptors by gingipains from Porphyromonas gingivalis leads to platelet aggregation: a new trait in microbial pathogenicity. Blood 97:3790–3797 [CrossRef]
    [Google Scholar]
  12. Mikolajczyk-Pawlinska J., Travis J., Potempa J. 1998; Modulation of interleukin-8 activity by gingipains from Porphyromonas gingivalis : implications for pathogenicity of periodontal disease. FEBS Lett 440:282–286 [CrossRef]
    [Google Scholar]
  13. Momose F., Araida T., Negishi A., Ichijo H., Shioda S., Sasaki S. 1989; Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. J Oral Pathol Med 18:391–395 [CrossRef]
    [Google Scholar]
  14. Naito M., Sakai E., Shi Y., Ideguchi H., Shoji M., Ohara N., Naito M., Yamamoto K., Nakayama K. 2006; Porphyromonas gingivalis -induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase. Mol Microbiol 59:152–167 [CrossRef]
    [Google Scholar]
  15. Nakayama K., Kadowaki T., Okamoto K., Yamamoto K. 1995; Construction and characterization of arginine-specific cysteine proteinase (Arg-gingipain)-deficient mutants of Porphyromonas gingivalis . Evidence for significant contribution of Arg-gingipain to virulence. J Biol Chem 270:23619–23626 [CrossRef]
    [Google Scholar]
  16. Nakayama K., Ratnayake D. B., Tsukuba T., Kadowaki T., Yamamoto K., Fujimura S. 1998; Haemoglobin receptor protein is intragenically encoded by the cysteine proteinase-encoding genes and the haemagglutinin-encoding gene of Porphyromonas gingivalis . Mol Microbiol 27:51–61 [CrossRef]
    [Google Scholar]
  17. O'Brien P. J., Molino M., Kahn M., Brass L. F. 2001; Protease activated receptors: theme and variations. Oncogene 20:1570–1581 [CrossRef]
    [Google Scholar]
  18. Ogawa T., Asai Y., Makimura Y., Tamai R. 2007; Chemical structure and immunobiological activity of Porphyromonas gingivalis lipid A. Front Biosci 12:3795–3812 [CrossRef]
    [Google Scholar]
  19. Okamoto K., Kadowaki T., Nakayama K., Yamamoto K. 1996; Cloning and sequencing of the gene encoding a novel lysine-specific cysteine proteinase (Lys-gingipain) in Porphyromonas gingivalis : structural relationship with the arginine-specific cysteine proteinase (Arg-gingipain). J Biochem (Tokyo) 120:398–406 [CrossRef]
    [Google Scholar]
  20. Pike R., McGraw W., Potempa J., Travis J. 1994; Lysine- and arginine-specific proteinases from Porphyromonas gingivalis . Isolation, characterization, and evidence for the existence of complexes with hemagglutinins. J Biol Chem 269:406–411
    [Google Scholar]
  21. Potempa J., Pike R., Travis J. 1995; The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain. Infect Immun 63:1176–1182
    [Google Scholar]
  22. Potempa J., Pike R., Travis J. 1997; Titration and mapping of the active site of cysteine proteinases from Porphyromonas gingivalis (gingipains) using peptidyl chloromethanes. Biol Chem 378:223–230
    [Google Scholar]
  23. Potempa J., Mikolajczyk-Pawlinska J., Brassell D., Nelson D., Thøgersen I. B., Enghild J. J., Travis J. 1998; Comparative properties of two cysteine proteinases (gingipains R), the products of two related but individual genes of Porphyromonas gingivalis . J Biol Chem 273:21648–21657 [CrossRef]
    [Google Scholar]
  24. Pütsep K., Carlsson G., Boman H. G., Andersson M. 2002; Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 360:1144–1149 [CrossRef]
    [Google Scholar]
  25. Sato K., Sakai E., Veith P. D., Shoji M., Kikuchi Y., Yukitake H., Ohara N., Naito M., Okamoto K. other authors 2005; Identification of a new membrane-associated protein that influences transport/maturation of gingipains and adhesins of Porphyromonas gingivalis . J Biol Chem 280:8668–8677 [CrossRef]
    [Google Scholar]
  26. Shi Y., Ratnayake D. B., Okamoto K., Abe N., Yamamoto K., Nakayama K. 1999; Genetic analyses of proteolysis, hemoglobin binding, and hemagglutination of Porphyromonas gingivalis . Construction of mutants with a combination of rgpA ,rgpB , kgp , and hagA . J Biol Chem 274:17955–17960 [CrossRef]
    [Google Scholar]
  27. Shoji M., Naito M., Yukitake H., Sato K., Sakai E., Ohara N., Nakayama K. 2004; The major structural components of two cell surface filaments of Porphyromonas gingivalis are matured through lipoprotein precursors. Mol Microbiol 52:1513–1525 [CrossRef]
    [Google Scholar]
  28. Sugawara S., Nemoto E., Tada H., Miyake K., Imamura T., Takada H. 2000; Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness. J Immunol 165:411–418 [CrossRef]
    [Google Scholar]
  29. Tada H., Sugawara S., Nemoto E., Takahashi N., Imamura T., Potempa J., Travis J., Shimauchi H., Takada H. 2002; Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production. Infect Immun 70:3304–3307 [CrossRef]
    [Google Scholar]
  30. Tada H., Sugawara S., Nemoto E., Imamura T., Potempa J., Travis J., Shimauchi H., Takada H. 2003; Proteolysis of ICAM-1 on human oral epithelial cells by gingipains. J Dent Res 82:796–801 [CrossRef]
    [Google Scholar]
  31. Tancharoen S., Sarker K. P., Imamura T., Biswas K. K., Matsushita K., Tatsuyama S., Travis J., Potempa J., Torii M., Maruyama I. 2005; Neuropeptide release from dental pulp cells by RgpB via proteinase-activated receptor-2 signaling. J Immunol 174:5796–5804 [CrossRef]
    [Google Scholar]
  32. Uehara A., Sugawara S., Tamai R., Takada H. 2001; Contrasting responses of human gingival and colonic epithelial cells to lipopolysaccharides, lipoteichoic acids and peptidoglycans in the presence of soluble CD14. Med Microbiol Immunol 189:185–192 [CrossRef]
    [Google Scholar]
  33. Uehara A., Sugawara S., Takada H. 2002a; Priming of human oral epithelial cells by interferon- γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans. J Med Microbiol 51:626–634
    [Google Scholar]
  34. Uehara A., Sugawara S., Muramoto K., Takada H. 2002b; Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2. J Immunol 169:4594–4603 [CrossRef]
    [Google Scholar]
  35. Uehara A., Muramoto K., Takada H., Sugawara S. 2003; Neutrophil serine proteinases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2. J Immunol 170:5690–5696 [CrossRef]
    [Google Scholar]
  36. Uehara A., Sugawara Y., Sasano T., Takada H., Sugawara S. 2004; Proinflammatory cytokines induce proteinase 3 as membrane-bound and secretory forms in human oral epithelial cells and antibodies to proteinase 3 activate the cells through protease-activated receptor-2. J Immunol 173:4179–4189 [CrossRef]
    [Google Scholar]
  37. Uehara A., Muramoto K., Imamura T., Nakayama K., Potempa J., Travis J., Sugawara S., Takada H. 2005; Arginine-specific gingipains from Porphyromonas gingivalis stimulate production of hepatocyte growth factor (scatter factor) through protease-activated receptors in human gingival fibroblasts in culture. J Immunol 175:6076–6084 [CrossRef]
    [Google Scholar]
  38. Weiss S. J. 1989; Tissue destruction by neutrophils. N Engl J Med 320:365–376 [CrossRef]
    [Google Scholar]
  39. Wingrove J. A., DiScipio R. G., Chen Z., Potempa J., Travis J., Hugli T. E. 1992; Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas ( Bacteroides ) gingivalis . J Biol Chem 267:18902–18907
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.47679-0
Loading
/content/journal/jmm/10.1099/jmm.0.47679-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed