Degradation of basement membrane collagen by proteases from some anaerobic oral microorganisms

Uitto, Veli‐Jukka; Haapasalo, Markus; Laakso, Tuula; Salo, Tuula

doi:10.1111/j.1399-302x.1988.tb00092.x

Cited by 65 publications

(60 citation statements)

References 36 publications

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“…Moreover, in our study, KDP128 was found to be ineffective in infiltrating connective tissue, in agreement with the results of Park and Lamont (32), who reported that an Arg-or Lys-gingipaindeficient mutant was 10-fold less invasive than the parent strain. P. gingivalis cysteine proteinase gingipains are important virulence factors that contribute to the pathogenesis of periodontitis and degrade extracellular matrix proteins, such as laminin, fibronectin, and type IV collagen (11,33,51). We extended studies on the direct contribution of P. gingivalis gingipains to the degradation of extracellular matrix proteins by using an in vitro reconstituted basement membrane model (Matrigel).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Models of Tissue Penetration and Destruction by Porphyromonas gingivalis

2004

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Porphyromonas gingivalis is a gram-negative anaerobic bacterium that is considered the key etiologic agent of chronic periodontitis. Arg-and Lys-gingipain cysteine proteinases produced by P. gingivalis are key virulence factors and are believed to be essential for significant tissue component degradation, leading to host tissue invasion by periodontopathogens. Two in vitro models were used to determine the extent to which P. gingivalis can reach connective tissue. The tissue penetration potential of P. gingivalis was first investigated by using an engineered human oral mucosa model composed of normal human epithelial cells and fibroblasts. Internalized bacteria were assessed by transmission electron microscopy. Bacteria were observed within multilayered gingival epithelial cells and in the space between the stratified epithelium and the lamina propria. A gingipainnull mutant strain of P. gingivalis was found to be less potent in penetrating tissue than the wild-type strain. Proinflammatory responses to P. gingivalis infection were evaluated. P. gingivalis increased the secretion of interleukin-1␤, interleukin-6, interleukin-8, and tumor necrosis factor alpha. In the second part of the study, the contribution of P. gingivalis gingipains to tissue penetration was investigated by using a reconstituted basement membrane model (Matrigel). The penetration of 14 C-labeled P. gingivalis cells through Matrigel was significantly reduced when leupeptin, a specific inhibitor of Arg-gingipain activity, was added or when a gingipain-null mutant was used. The results obtained with these two relevant models support the capacities of P. gingivalis to infiltrate periodontal tissue and to modulate the proinflammatory response and suggest a critical role of gingipains in tissue destruction.

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Section: Discussionmentioning

confidence: 99%

In Vitro Models of Tissue Penetration and Destruction by Porphyromonas gingivalis

2004

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“…P. gingivalis protease has been suggested to contribute to the development of periodontal disease in various ways, i.e. degrading the connective tissues (Uitto et al, 1988), binding to fibronectin and laminin (Pike et al, 1996), inactivating immunoglobulins (Grenier et al, 1989;Sato et al, 1987) and the complement systems (Grenier and McBride, 1987), activating the kallikrein cascade (Nilsson et al, 1985), or disrupting the functions of the polymorphonuclear leukocytes (Yoneda et al, 1990). In addition, P. gingivalis protease may act as a processing protease responsible for the maturation of fimbriae (Nakayama et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Adherence of Porphyromonas gingivalis to matrix proteins via a fimbrial cryptic receptor exposed by its own arginine‐specific protease

Kontani

Kimura

Nakagawa

et al. 1997

Molecular Microbiology

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SummaryPorphyromonas gingivalis, a Gram-negative anaerobe, is known to be involved in the pathogenesis of periodontitis. P. gingivalis fimbriae, which are proteinaceous appendages extending from the cell surface, may contribute to the adherence of the organism to the host cell surface. We previously suggested that arginine-specific protease produced by P. gingivalis enhanced the adherence of purified fimbriae to fibroblasts or matrix proteins. In this study, we have revealed the mechanism of the enhanced binding of fimbriae by the protease in more detail. Arg-specific protease and fimbriae were obtained from P. gingivalis 381 cells and purified. We then analysed the interaction of fimbriae and immobilized fibronectins (intact or partially degraded fibronectin by the purified protease) by using the real-time biomolecular interaction analysis (BIAcore) system with an optical biosensor based on the principles of surface plasmon resonance. BIAcore profiles demonstrated an enhanced interaction between fimbriae and protease-degraded fibronectin. We also showed specific binding of fimbriae to the degraded fibronectin by means of BIAcore analysis. The binding of biotinylated fimbriae to immobilized fibronectin was examined by enzymelinked biotin-avidin assay. The purified protease enhanced the fimbrial binding to the immobilized fibronectin. The enhancement was inhibited by the addition of L-Arg, or oligopeptides containing the Arg residue at the C-terminus in the fimbrial binding reaction, suggesting that the P. gingivalis fimbriae may potentially have an ability to bind tightly to the Arg residue at C-terminus. Taken together, these studies indicate that P. gingivalis arginine-specific protease can expose a cryptitope in the matrix protein molecules, i.e. the C-terminal Arg residue of the host matrix proteins, so that the organism can adhere to the surface layer in the oral cavity through fimbriae-Arg interaction (a novel host-parasite relationship).

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“…Mutual symbiotic growth enhancement of T. denticola and P. gingivalis is another potential periodontal Porphyromonas gingivalis pathogen [15,16] 14. Activation of host latent procollagenase (T. denticola, Suggests that spirochaetal enzymes participate oral spirochetes) directly in tissue destruction [65,72,74] 15. Direct degradation of basement membrane collagen As above [74] (T. denticola) 16.…”

Section: Suppression Of Fibroblast Proliferationmentioning

confidence: 99%

The peptidolytic capacity of the spirochete system

Mäkinen

Mäkinen²

1996

Med Microbol Immunol

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Relatively scant chemical information has been available on the proteinases and peptidases of spirochetes in spite of the association of spirochetes with several serious infections known to plague humans and other animal species. This situation has partly resulted from difficulties in growing some spirochetes under laboratory conditions. The cells of Treponema denticola, a spirochete suggested to be associated with periodontal infections, have turned out to be a good source of new chemical information on those enzymes. Latest studies suggest that the outer cell envelope or the periplasmic space of T. denticola contains several novel proteinases and peptidases (hence called "ectoenzymes") which may contribute to the chronicity of periodontal infections. Some of the oligopeptidases discovered are specific for proline-containing host tissue peptides such as substance P, bradykinin, neurotensin, etc., and possibly small collagen fragments. The only spirochetal peptidases purified to give a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis have been obtained from T. denticola. One particular peptidase, suggested to be similar to the oligopeptidase B (EC 3.4.21.83) of Escherichia coli seems to be present in the cell envelope or in the periplasmic space at quite large concentrations. The presence of this and several other peptidases in the outer cell structures of the treponemes suggests that such enzymes are important for the nutrition of these highly motile and invasive organisms. The biological role of these enzymes can thus be envisaged in the peptidolytic processing of host tissue proteins and peptides to gradually smaller molecules to fulfill the nutritional requirements of these organisms. Although the genetic similarity between T. denticola and some other treponemes and spirochetes can be hotly debated, it is nevertheless now possible to use T. denticula enzymes as suitable objects for comparison when the chemistry of other spirochetes is studied.

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Degradation of basement membrane collagen by proteases from some anaerobic oral microorganisms

Cited by 65 publications

References 36 publications

In Vitro Models of Tissue Penetration and Destruction by Porphyromonas gingivalis

In Vitro Models of Tissue Penetration and Destruction by Porphyromonas gingivalis

Adherence of Porphyromonas gingivalis to matrix proteins via a fimbrial cryptic receptor exposed by its own arginine‐specific protease

The peptidolytic capacity of the spirochete system

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