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- Material Type
- 文書・図像類
- Author/Editor
- 町頭, 三保
- Author Heading
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- Alternative Title
- The development of a new therapy for periodontitis by regulation of TNF family members
- Text Language Code
- jpn
- Subject Heading
- Target Audience
- 一般
- Note (General)
- 2009-2011年度科学研究費助成事業(科学研究費補助金(基盤研究(C)))研究成果報告書 課題番号：21592628 研究代表者：町頭三保 (鹿児島大学医学部・歯学部附属病院講師)TNF-αはプロサイトカインの一つで、炎症反応で重要な役割を担っており、その前駆体はTACEとよばれるメタロプロテアーゼにより活性化される。TNF-αは歯周病の発症と進行にも深く関与している。今回、TNF-αの産生抑制による歯周病治療薬を開発する目的で、TACE阻害剤とエピガロカテキンガレート（EGCG）の有効性を評価した。TACEはヒト歯肉炎症組織のマクロファージと歯肉線維芽細胞に存在した。ACE阻害剤とEGCGは、THP-1細胞におけるTNFαの産生を用量依存的に抑制し、特にEGCGは高濃度のグルコース存在下でTNF-αの産生抑制効果が高かった。さらにラット歯周病モデルにおいて、TACE阻害剤は歯槽骨吸収抑制効果を示した。TACE inhibitorとEGCGは、ヒト歯周炎治療の魅力的なターゲットである。TNF-α is a proinflamatory cytokine, plays a pivotal role in the inflammatory reaction. Its precursor is cleaved by a metalloprotease named TNF-α-converting enzyme (TACE) to generate the mature TNF-α. The aim of this study is to generate a potent anti-inflammatory drug, TACE inhibitor and epigallocatechin 3 gallate(EGCG) to periodontitis where TNF- αis thought to be pathologically indicated. TACE immunopositively localized mainly in macrophages and gingival fibroblast in inflamed human gingival tissues. The TACE inhibitor and EGCG eliminated kinetics of LPS-induced TNF- α secretion in a dose-dependent manner by ELISA. Furthermore, EGCG showed more strong inhibitory effect under high glucose conditions. TACE reduced alveolar bone loss in a rat model of P. gingivalis-induced periodontitis. TACE inhibitor and EGCG appear to be an attractive target for treating human periodontitis.