TODENTJ-25-03-2019_TODENTJ-2-96 1553505008 Bentham Open doi@benthamopen.net Bentham Open The Open Dentistry Journal TODENTJ 1874-2106 7 9 2008 2 1 Guang Jie Bao Kirsti Kari Taina Tervahartiala Timo Sorsa Jukka H. Meurman Tissue reactions to bacteria lead to proinflammatory reactions involving matrix metalloproteinases (MMPs). Synthetic protease inhibitors may offer new possibilities to regulate bacterial proteases. We investigated proteolytic activities of certain periodontal bacteria, their effects on the latent proMMP-9, and the effects of synthetic MMP inhibitors and a serine protease inhibitor Pefabloc. The strains studied were Porphyromonas gingivalis, Prevotella intermedia, Peptostreptoccus micros, Prevotella nigrescens, Fusobacterium nucleatum, and 5 Aggregatibacter actinomycetemcomitans serotypes. Their gelatinolytic activities and the effects of certain synthetic MMP inhibitors and Pefabloc were analyzed by zymography. Bacterial effects on proMMP-9 conversion were investigated by Western immunoblot. All investigated periodontal bacteria produced gelatinolytic cell-bound and extracellular proteinases which could fragment latent proMMP-9, suggesting co-operative processing cascades in oral tissue remodeling. A. actinomycetemcomitans produced the weakest gelatinolytic activity. Synthetic proteinase inhibitors exhibited slight but clear reductive effects on the bacterial proteolytic activities. We conclude that targeted anti-proteolytic treatment modalities against bacterial-host proteolytic cascades can be developed. 7 9 2008 96 102 TODENTJ-2-96 1 10.2174/crossmark_policy opendentistryjournal.com benthamopen.com true Peer Reviewed Single blind Checked with iThenticate 2008-1-14 2008-6-5 2008-6-5 2008-7-9 http://creativecommons.org/licenses/by/2.5/ 10.2174/1874210600802010096 1553505008 https://opendentistryjournal.com/VOLUME/2/PAGE/96/ https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.pdf https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.pdf https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.pdf https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.pdf https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.pdf https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.pdf https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.pdf https://opendentistryjournal.com/contents/volumes/V2/TODENTJ-2-96/TODENTJ-2-96.xml Oral Dis Sorsa T 10 311 2004 Sorsa T, Tjäderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases Oral Dis 2004; 10 : 311-8. Periodontol Uitto VJ 31 77 2003 Uitto VJ, Overall CM, McCulloch C. Proteolytic host cell enzymes in gingival crevice fluid Periodontol 2003; 31 : 77-104. N Engl J Med Weiss SJ 320 365 1990 Weiss SJ. Tissue destruction by neutrophils N Engl J Med 1990; 320 : 365-76. J Periodontol Mancini S 70 1292 1999 Mancini S, Romanelli R, Laschinger CA, Overall CM, Sodek J, McCulloch CA. Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases J Periodontol 1999; 70 : 1292-302. Infect Immun Romanelli R 67 2319 1999 Romanelli R, Mancini S, Laschinger C, Overall CM, Sodek J, McCulloch CA. Activation of neutrophil collagenase in periodontitis Infect Immun 1999; 67 : 2319-26. J Periodontal Res Lee W 30 23 1995 Lee W, Aitken S, Sodek J, McCulloch CA. Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo role of active enzyme in human periodontitis J Periodontal Res 1995; 30 : 23-33. J Periodont Res Mäntylä P 38 436 2003 Mäntylä P, Stenman M, Kinane DF, et al. Gingival crevicular fluid collagenase-2 (MMP-8) test stick for chair-side monitoring of periodontitis J Periodont Res 2003; 38 : 436-9. J Immunol Owen CA 172 7791 2004 Owen CA, Hu Z, Lopez-Otin C, Shapiro SD. Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent tissue inhibitor of metalloproteinase-resistant collagenase and serpinase J Immunol 2004; 172 : 7791-803. J Clin Periodontol Sorsa T 22 709 1995 Sorsa T, Ding YL, Ingman T, et al. Cellular source, activation and inhibition of dental plaque collagenase J Clin Periodontol 1995; 22 : 709-17. J Clin Periodontol Söder B 29 384 2002 Söder B, Jin LJ, Wickholm S. Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitis J Clin Periodontol 2002; 29 : 384-91. J Intern Med Tayebjee MH 257 110 2005 Tayebjee MH, Tan KT, MacFadyen RJ, Lip GY. Abnormal circulating levels of metalloproteinase 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease relationship to disease severity J Intern Med 2005; 257 : 110-6. Eur J Clin Invest Kalela A 30 99 2000 Kalela A, Ponnio M, Koivu TA, et al. Association of serum sialic acid and MMP-9 with lipids and inflammatory markers Eur J Clin Invest 2000; 30 : 99-104. J Periodont Res Söder B 41 411 2006 Söder B, Airila Månsson S, Kari K, Meurman JH. Levels of matrix metalloproteinases -8 and -9 with simultaneous presence of periodontal pathogens in gingival crevicular fluid as well as matrix metalloproteinase-9 and cholesterol in blood J Periodont Res 2006; 41 : 411-7. Arch Oral Biol Kubota T 41 253 1996 Kubota T, Nomura T, Takahashi T, Hara K. Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in periodontitis-affected human gingival tissue Arch Oral Biol 1996; 41 : 253-62. J Bacteriol Paster BJ 183 3770 2001 Paster BJ, Boches SK, Galvin JL, et al. Bacterial diversity in human subgingival plaque J Bacteriol 2001; 183 : 3770-83. Ann Periodontol Listgarten MA 8 182 2003 Listgarten MA, Loomer PM. Microbial identification in the management of periodontal diseases A systematic review Ann Periodontol 2003; 8 : 182-92. Adv Dent Res Golub LM 12 12 1998 Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T. Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms Adv Dent Res 1998; 12 : 12-26. J Biol Chem Sorsa T 272 21067 1997 Sorsa T, Salo T, Koivunen E, et al. Activation of type IV procollagenases by human tumor-associated trypsin-2 J Biol Chem 1997; 272 : 21067-74. Nat Biotech Koivunen E 17 768 1999 Koivunen E, Arap W, Valtanen H, et al. Tumor targeting with a selective gelatinase inhibitor Nat Biotech 1999; 17 : 768-74. Oral Microbiol Immunol Garlet GP 21 12 2006 Garlet GP, Cardoso CR, Silva TA, et al. Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors Oral Microbiol Immunol 2006; 21 : 12-20. Periodontol Eley BM 31 105 2003 Eley BM, Cox SW. Proteolytic and hydrolytic enzymes from putative periodontal pathogens characterization molecular genetics effects on host defences and tissues and detection in gingival crevice fluid Periodontol 2003; 31 : 105-24. Periodontol Potempa J 24 153 2000 Potempa J, Banbula A, Travis J. Role of bacterial proteinases in matrix destruction and modulation of host responses Periodontol 2000; 24 : 153-92. J Dent Res De Carlo AA 76 1260 1997 De Carlo AA, Windsor LJ, Boden MK, Harber GJ, Birkedal-Hansen B, Birkedal-Hansen H. Activity and novel processing of matrix metalloproteinases by a thiolproteinase from the oral anaerobe Porphyromonas gingivalis J Dent Res 1997; 76 : 1260-70. Oral Microbiol Immunol Fujimura S 4 227 1989 Fujimura S, Nakamura T. Multiple forms of proteinases of Bacteroides gingivalis and their cellular location Oral Microbiol Immunol 1989; 4 : 227-9. Arch Oral Biol Gazi MI 41 393 1996 Gazi MI, Cox SW, Clark DT, Eley BM. A comparison of cysteine and serine proteinases in human gingival crevicular fluid with host tissue, saliva and bacterial enzymes by analytical isoelectric focusing Arch Oral Biol 1996; 41 : 393-400. Oral Microbiol Immunol Gazi MI 12 240 1997 Gazi MI, Cox SW, Clark DT, Eley BM. Characterisation of proteinase activities in Capnocytophage spp Porphyromonas gingivalis Prevotella spp Treponema denticola and Actinobacillus actinomycetemcomitans Oral Microbiol Immunol 1997; 12 : 240-8. J Periodontal Res Travis J 32 120 1997 Travis J, Pike R, Imamura T, Potempa J. Porphyromonas gingivalis proteinases as virulence factors in the development of chronic periodontistis J Periodontal Res 1997; 32 : 120-5. J Periodontal Res Lantz MS 28 467 1993 Lantz MS, Allen RD, Chiorowski PK, Holt CS. Purification and immunolocalisation of a cysteine proteinase from Porphyromonas gingivalis J Periodontal Res 1993; 28 : 467-9. J Biol Chem Chen Z 267 18896 1992 Chen Z, Potempa J, Polanowski A, Wikström M, Travis J. Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis J Biol Chem 1992; 267 : 18896-901. J Bacteriol Kato T 174 3889 1992 Kato T, Takahashi N, Kuramitsu H. Sequence analysis and characterization of the Porphyromonas gingivalis ptrC gene, which expresses a novel collagenase activity J Bacteriol 1992; 174 : 3889-95. Infect Immun Lawson DA 60 1524 1992 Lawson DA, Meyer TE. Biochemical characterization of Porphyromonas (Bacteroides) gingivalis collagenase Infect Immun 1992; 60 : 1524-9. Infect Immun Sojar HT 61 2369 1993 Sojar HT, Lee J-Y, Bedi GS, Genco RJ. Purification and characterization of a proteinase from Porphyromonas gingivalis capable of degrading salt-solubilized collagen Infect Immun 1993; 61 : 2369-76. Oral Microbiol Immun Uitto VJ 3 97 1988 Uitto VJ, Haapasalo M, Laakso T, Salo T. Degradation of basement membrane collagen by proteinases from some anaerobic oral microorganisms Oral Microbiol Immun 1988; 3 : 97-102. Eur J Oral Sci Wang P-L 107 147 1999 Wang P-L, Shirasu S, Shinohara M, et al. Purification and characterization of a trypsin-like proteinase form the culture supernatant of Actinobacillus actinomycetemcomitans Y4 Eur J Oral Sci 1999; 107 : 147-53. J Dent Res Rozanis J 62 300 1983 Rozanis J, Van Wart HE, Bond MB, Slots J. Further studies on collagenase of Actinobacillus actinomycetemcomitans J Dent Res 1983; 62 : 300. Oral Microbiol Immun Bachrach G 19 155 2004 Bachrach G, Rosen M, Bellalou M, Naor R, Sela MN. Identification of a Fusobacterium nucleatum 65kDa serine proteinase Oral Microbiol Immun 2004; 19 : 155-9. Ann Med Sorsa T 38 306 2006 Sorsa T, Tjäderhane L, Konttinen YT, et al. Matrix metalloproteinases contribution to pathogenesis, diagnosis and treatment of periodontal inflammation Ann Med 2006; 38 : 306-21. Crit Rev Biochem Mol Biol Van den Steen PE 37 375 2002 Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9) Crit Rev Biochem Mol Biol 2002; 37 : 375-536. J Biol Chem Okamoto T 272 6059 1997 Okamoto T, Akaike T, Suga M, et al. Activation of human matrix metalloproteinases by various bacterial proteinases J Biol Chem 1997; 272 : 6059-66. J Immunol Min D 168 2449 2002 Min D, Moore AG, Bain MA, Breit SN, Lyons JG. Activation of macrophage promatrix metalloproteinase-9 by lipopolysaccharide-associated proteinases J Immunol 2002; 168 : 2449-55. J Periodontol Seguier S 72 1398 2001 Seguier S, Gogly B, Bodineau A, Godeau G, Brousse N. Is collagen breakdown during periodontistis linked to inflammatory cells and expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival tissue? J Periodontol 2001; 72 : 1398-406. Annal Biochem Neumann U 328 166 2004 Neumann U, Kubota H, Frei K, Ganu V, Leppert D. Charaterization of Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg NH2 a fluorogenic substrate with increased specificity constants for collagenases and tumor necrosis factor converting enzyme Annal Biochem 2004; 328 : 166-73. J Peridont Res Pozo P 40 199 2005 Pozo P, Valenzuela MA, Melej C, et al. Longitudinal analysis of metalloproteinases tissue inhibitors of metalloproteinases and clinical parameters in gingival crevicular fluid from periodontitis-affected patients J Peridont Res 2005; 40 : 199-207. Antimicrob Agents Chemother Imamura T 45 2871 2001 Imamura T, Matsushita K, Travi J, Potempa J. Inhibition of trypsin-like cysteine proteinases (4 gingipains) from Porphyromonas gingivalis by tetracycline and its analogues Antimicrob Agents Chemother 2001; 45 : 2871-6. J Periodont Res Claesson R 37 353 2002 Claesson R, Johansson A, Belibasakis G, Hanström L3, Kalfas S. Release and activation of matrix metalloproteinase-8 from human neutrophils triggered by the leukotoxin of Actinobacillus actinomycetemcomitans J Periodont Res 2002; 37 : 353-9. Oral Microbiol Immunol Grenier D 21 190 2006 Grenier D, Grignon L. Response of human macrophage-like cells to stimulation by Fusobacterium nucleatum ssp.nucleatum lipopolysaccharide Oral Microbiol Immunol 2006; 21 : 190-6. J Periodontol Grenier D 73 1316 2003 Grenier D, Roy E, Mayrand D. Modulation of Porphyromonas gingivalis proteinase activity by suboptimal doses of antimicrobial agents J Periodontol 2003; 73 : 1316-9.