Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leucocyte protease inhibitor in periodontal tissue.
Chronic periodontitis is correlated with Porphyromonas gingivalis infection. In this study, we found that the expression of secretory leucocyte protease inhibitor (SLPI), an endogenous inhibitor for neutrophil-derived proteases, was reduced in gingival tissues with chronic periodontitis associated with P. gingivalis infection. The addition of vesicles of P. gingivalis decreased the amount of SLPI in the media of primary human gingival keratinocytes compared to untreated cultures. We therefore investigated how arginine-specific gingipains (Rgps) affect the functions of SLPI, because Rgps are the major virulence factors in the vesicles and cleave a wide range of in-host proteins. We found that Rgps digest SLPI in vitro, suppressing the release of SLPI. Rgps proteolysis of SLPI disrupted SLPI functions, which normally suppresses neutrophil elastase and neutralizes pro-inflammatory effects of bacterial cell wall compounds in cultured human gingival fibroblasts. The protease inhibitory action of SLPI was not exerted towards Rgps. These results suggest that Rgps reduce the protective effects of SLPI on neutrophil proteases and bacterial proinflammatory compounds, by which disease in gingival tissue may be accelerated at the sites with P. gingivalis infection.
Into
T
T
Department of Oral Disease Research, National Institute for Longevity Sciences, Obu, Aichi, Japan.
Inomata
M
M
Kanno
Y
Y
Matsuyama
T
T
Machigashira
M
M
Izumi
Y
Y
Imamura
T
T
Nakashima
M
M
Noguchi
T
T
Matsushita
K
K
D018829:Adhesins, Bacterial / Q000032:analysis / Q000494:pharmacology*; D002478:Cells, Cultured; D002908:Chronic Disease; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000494:pharmacology*; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D000080867:Gingipain Cysteine Endopeptidases; D005881:Gingiva / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D005883:Gingival Crevicular Fluid / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D015151:Immunoblotting; D016209:Interleukin-8 / Q000032:analysis; D008875:Middle Aged; D010518:Periodontitis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000502:physiology*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor; D018709:Statistics, Nonparametric
D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D016209:Interleukin-8; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D003546:Cysteine Endopeptidases