| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Kuniaki Nagasaki Univ. Dept. of Pharmacol, Associ. Prof, 歯学部, 助教授 (10311846)
TSUKUBA Tomoko Kyushu Univ. Dept. of Pharmacol, Assist. Prof, 大学院・歯学研究院, 助手 (70336080)
TSUKUB Takayuki Kyushu Univ. Dept. of Pharmacol, Associ. Prof, 大学院・歯学研究院, 助教授 (30264055)
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| Research Abstract |
Periodontitis is an infectious diseases associated with a loss of connective tissue, resorption of alveolar bone, and formation of periodontal pockets. Porphyromonas gingivalis is one of the most important pathogens for the disease and produces two major cysteine proteinases, Arg-gingipain (Rgp) and Lys-gingipain (Kgp), in both secretory and cell-associated forms. Recent studies suggest that these enzymes are involved in the pathogenesis of periodontal disease through various mechanisms, such as direct destruction of periodontal tissue components, disruption of host defense mechanisms, processing of adhesion molecules and production of inflammatory mediators. In this study, we provide evidence that Rgp anf Kgp cooperatively function with respect to the disruption of periodontal connective tissue integrity induced by the bacterium, the adhesion of the bacterium to host tissue components, the proliferation and growth of the bacterium in periodontal pockets, the hemagglutination and colon
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ization of the bacterium, and the disruption of cytokine responses and loss of viability of endothelial cells by the bacterium. On the other hand, we noticed that the lysosomal aspartic proteinase cathepsin D-deficient mice showed a progressive atrophy of the intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin, and developed a neurological phenotype resembling neuronal ceroid lipofusinosis. These results suggest that cathepsin D is essential for proteolysis of proteins regulating cell growth and tissue homeostasis. Cathepsin E is a homologous enzyme to cathepsin D. In contrast to cathepsin D, cathepsin E has a limited distribution and a cellular localization. In macrophages and microglia, we found that cathepsin E was responsible for the processing of exogenous antigens followed by the MHC class II-mediated antigen presentation. The present study provides evidence that proteinase inhibitors for Rgp and Kgp and factors regulating cathepsins D and E may provide a mean of preventing the onset and development of periodontal diseases. Less
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