|Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
The periodontal disease is a chronic inflammation caused mainly by Porphyromonas gingivalis infection. The trypsin-like cysteine proteinases produced from the bacterium (gingipains; HRgpA, RgpB and Kgp) are major virulence factors and may be associated the bacterial survival and periodontal tissue breakdown. Hence, the effects of gingipains on the host-defense system and tissue destruction through modulating cell functions. Gingipains destroyed CD4 and CD8 on the human T lymphocytes at 0.1 μM in 30 min. They also cleaved off gingival fibroblast CD14, which recognizes LPS and activates the cells, attenuating the release of IL-8, a neutrophil chemotactic factor. These results indicated that gingipains cleaves receptors of host immune cells, facilitating the escape of the bacterium from these cells. The gingival tissue with periodontitis increased expression matrix metalloproteinase (MMP)-1, -2 and -9. Therefore, the effect of gingipains on cultured gingival cell MMP production was investigated. Gingival fibroblast MMP-1 production increased 2.5 and 2-fold by addition of 1nM HRgpA or RgpB, respectively. Neutrophils released 7 or 1.3-fold more MMP-1 by HRgpA or RgpB, respectively. MMP-2 production by gingival epithelial cells increased 5-fold by 0.1 nM RgpB or 1 nM HRgpA. Taken together, gingipains R stimulate MMP production by gingival cells and neutrophils, which promotes gingival tissue destruction. The fact that factor Xa-specific inhibitor, DX9065a inhibited these gingipain R activities suggested a possible therapeutic effect of proteinase inhibitors on periodontitis.