Study of drug development targetting ADAMs in gingival epithelium for prevention of peridontal diseases

• Project/Area Number: 15K11424
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Social dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: Awano Shuji 九州歯科大学, 歯学部, 教授 (20301442)
• Co-Investigator(Kenkyū-buntansha): 邵 仁浩 九州歯科大学, 歯学部, 講師 (10285463) ; 安細 敏弘 九州歯科大学, 歯学部, 教授 (80244789) ; 岩崎 正則 九州歯科大学, 歯学部, 准教授 (80584614) ; 角田 聡子 九州歯科大学, 歯学部, 助手 (70364156)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 歯周病予防 / メタロプロテアーゼ / TNF-α / ADAM17 / TNF -α転換酵素 / 歯周疾患 / TNFα-converting enzyme / TNFα / ヒト口腔ケラチノサイト / 歯周組織 / 歯周炎

Outline of Final Research Achievements

A disintegrin and metalloprotease 17 (ADAM17), one of proteases belonging ADAMs family, is a tumor necrosis factor (TNF)-converting enzyme that cleaves the prodomain of TNF-α, a proinflammatory cytokine that plays a central role in immune regulation and a variety of inflammatory responses in destructive periodontal disease. This study verified the possibility of ADAM17 in the gingival epithelium as a target for drug development to prevent periodontal diseases.
Strong immunoreactivity for ADAM17 was observed in the epithelium of the inflamed gingival tissues and in in human oral keratinocytes (HOKs). Furthermore, treatment with either ADAM17 inhibitor or ADAM17 siRNA inhibited the generation of TNF-α induced by lipopolysaccharide (LPS) in HOKs. The present study demonstrates that ADAM17 is strongly expressed in the epithelium of gingival tissues and suggests that ADAM17 may be a key enzyme that regulates the generation of TNF-α in oral keratinocytes.

Research Products

• [Journal Article] <b>ADAM17 regulates TNF-α expression upon lipopolysaccharide stimulation in oral </b><b>keratinocytes </b> (2017)
  • Author(s): Hirayama A, Awano S, Seta Y, Ansai T.
  • Journal Title: Biomedical Research Volume: 38 Issue: 3 Pages: 157-165
  • DOI: 10.2220/biomedres.38.157
  • NAID: 130006865608
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ADAM17 regulates TNF-α expression upon lipopolysaccharide stimulation in oral keratinocytes (2017)
  • Author(s): Hirayama A, Awano S, Seta Y, Ansai T
  • Journal Title: Biomedical Research Volume: 印刷中
  • NAID: 130006865608
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 歯周組織におけるa disintegrin and metalloprotease 17について． (2015)
  • Author(s): 村野 綾、粟野秀慈、吉田明弘、邵 仁浩、安細敏弘
  • Organizer: 第63回日本口腔衛生学会・総会
  • Place of Presentation: 熊本市
  • Year and Date: 2015-05-29
• [Presentation] 歯周組織におけるa disintegrin and metalloproteinase 17の局在性について． (2015)
  • Author(s): 村野 綾、粟野秀慈、瀬田裕司、吉田明弘、邵 仁浩、豊島邦昭、安細敏弘
  • Organizer: 第73回九州歯科学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2015-05-18
• [Remarks] ADAM17 regulates TNF-α expression
  • URL: https://doi.org/10.2220/biomedres.38.157