Effect of IL-1Ra in periodontal tissue destruction with IL-1Ra-deficient mice

• Project/Area Number: 24593137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Matsumoto Dental University (2014); Aichi Gakuin University (2012-2013)
• Principal Investigator: ISHIHARA YUICHI 松本歯科大学, 歯学部, 教授 (50261011)
• Co-Investigator(Kenkyū-buntansha): NOGUCHI Toshihide 愛知学院大学, 歯学部, 教授 (50014262) ; MITANI Akio 愛知学院大学, 歯学部, 教授 (50329611) ; OZAWA Yusuke 愛知学院大学, 歯学部, 非常勤助教 (50624326)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: インターロイキンー１ / インターロイキンー１レセプターアンタゴニスト / 遺伝子改変マウス / 実験的歯周炎 / 炎症性骨吸収 / サイトカイン / 歯周治療薬 / インターロイキンー１Ra / 遺伝子欠損マウス / 骨吸収因子 / IL-1 / IL-1Ra / A. actinomycetemcomitans / TNF-α / IL-6 / 骨関連遺伝子 / 破骨細胞 / 骨芽細胞 / 接着分子 / RNA干渉

Outline of Final Research Achievements

The interleukin (IL)-1 receptor antagonist (Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is unclear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout (KO) mice vs wild type (WT) mice. Computed tomography (CT) analysis, and hematoxylin eosin (H&E) and tartrate resistant acid phosphatase (TRAP) staining were performed.Infected IL-1Ra KO mice exhibited bone loss in furcation areas and alveolar fenestrations.
Considering from the all results, IL-1Ra inflammatory bone resorption in experimental periodontitis induced by A. actinomycetemcomitans down-osteoclast differentiation and up-osteoblast differentiation and calcification. In short, these data suggest that an IL-1Ra may serve as a potential therapeutic drug for periodontal disease.

Research Products

• [Journal Article] Interleukin-1 receptor gene variants are associated with aggressive periodontitis in the Japanese (2014)
  • Author(s): Kamei H、Ishihara Y, 12 others
  • Journal Title: Arch Oral Biol Volume: Vol. 59、No. 7 Issue: 7 Pages: 756-763
  • DOI: 10.1016/j.archoralbio.2014.04.006
  • Peer Reviewed
• [Journal Article] Effect of IL-15 and natural killer cells on osteoclast and osteoblast in a mouse coculture (2014)
  • Author(s): Takeda H, Kikuchi T, Soboku K, Okabe I, Mizutani H, Mitani A, Ishihara Y, Noguchi T
  • Journal Title: Inflammation Volume: 37 Issue: 3 Pages: 657-669
  • DOI: 10.1007/s10753-013-9782-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] IL-1 Receptor Type II Production IsUpregulated by IL-4 and IL-13, andDownregulated by IFN-g in Mouse Gingival Epithelial Cells (2014)
  • Author(s): Kamiya Y, Ishihara Y, Kamei H, Ozawa Y, Mizutani H, Kubo K, Maeda H, Noguchi T.
  • Journal Title: Modern Research in Inflammation Volume: 3 Pages: 37-47
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory bone loss in experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout mice. (2014)
  • Author(s): Izawa A, Ishihara Y, Mizutani H, Kobayashi S, Goto H, Okabe E, Takeda H, Ozawa Y, Kamiya Y, Sugita Y, Kubo K, Kamei H, Kikuchi T, Mitani A, Hayashi J, Nishihara T, Maeda H, Noguchi T.
  • Journal Title: Infect Immun Volume: 82 Issue: 5 Pages: 1904-1913
  • DOI: 10.1128/iai.01618-13
  • Peer Reviewed
• [Journal Article] IL-1ファミリーとIL-1受容体：歯周病疾患マーカーや治療薬としての可能性 (2014)
  • Author(s): 石原裕一，亀井英彦，神谷洋介，伊澤有郎，水谷大樹，鈴木万里代，野口俊英，三谷章雄
  • Journal Title: 日歯周誌 Volume: 56 Pages: 272-280
  • NAID: 130004842577
• [Journal Article] IL-1 Receptor Type II Production Is Upregulated by IL-4 and IL-13, and Downregulated by IFN-γ in Mouse Gingival Epithelial Cells (2014)
  • Author(s): Kamiya Y, Ishihara Y, Kamei H, Ozawa Y, Mizutani H, Kubo K, Maeda H, Noguchi T
  • Journal Title: Modern Research in Inflammation Volume: 3 Issue: 02 Pages: 37-47
  • DOI: 10.4236/mri.2014.32005
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide of Aggregatibacter actinomycetemcomitans up-regulates inflammatory cytokines, prostaglandin E2 synthesis and osteoclast formation in interleukin-1 receptor antagonist-deficient mice (2013)
  • Author(s): Mizutani H, Ishihara Y, Izawa A, Fujihara Y, Kobayashi S, Gotou H, Okabe E, Takeda H, Ozawa Y, Kamiya Y, Kamei H, Kikuchi T, Yamamoto G, Mitani A, Nishihara T, Noguchi T.
  • Journal Title: J Periodont Res Volume: 48 Issue: 6 Pages: 748-756
  • DOI: 10.1111/jre.12065
  • Peer Reviewed
• [Presentation] インターロイキン１レセプターアンタゴニストのコラゲナーゼ３(MMP-13)発現抑制について (2014)
  • Author(s): 後藤久嗣、石原裕一、伊澤有郎、岡部栄次郎、久保勝俊、杉田好彦、前田初彦、野口俊英、三谷章雄
  • Organizer: 第85回愛知学院大学歯学会
  • Place of Presentation: 愛知学院大学楠元キャンパス(愛知)
  • Year and Date: 2014-12-07
• [Presentation] Interleukin-1 receptor antagonist は歯肉上皮細胞からのMatorix metallopeptidase 13 発現を抑制する. (2014)
  • Author(s): 後藤久嗣，石原裕一，伊澤有郎，岡部栄治郎，久保勝俊，杉田好彦，前田初彦，野口俊英，三谷章雄
  • Organizer: 秋季日本歯周病学会学術大会
  • Place of Presentation: 神戸国際展示場(兵庫)
  • Year and Date: 2014-10-19
• [Presentation] High levels of sIL-1RAcP was observed in chronic periodontitis patients. (2014)
  • Author(s): Kamiya Y, Ishihara Y, Kamei H, Izawa A, Okabe E, Goto H, Kuno A, Sugawa Y, Ozawa Y Mitani A
  • Organizer: 2014 Annual Meeting of American Academy of Periodontology
  • Place of Presentation: Moscone center, San Francisco, USA
  • Year and Date: 2014-09-19
• [Presentation] IL-1Receptor antagonist のRNA干渉がヒト歯肉上皮細胞の接着分子発現へ及ぼす影響
  • Author(s): 後藤久嗣，石原裕一，伊澤有郎，岡部栄治郎，久保勝俊，杉田好彦，前田初彦，野口俊英
  • Organizer: 第56回秋季日本歯周病学会
  • Place of Presentation: 前橋（群馬）
• [Presentation] 末梢血血清中の可溶性インターロイキン－１補助タンパクの歯周病マーカーとしての可能性
  • Author(s): 小澤佑介，石原裕一，亀井英彦，水谷大樹，伊澤有郎，岡部栄治郎，後藤久嗣，久野 茜，須川雄司，猪子将成，神谷洋介，野口俊英
  • Organizer: 第8回日本歯周病学会中部地区大学・日本臨床歯周病学会中部支部合同研究会
  • Place of Presentation: 松本（長野）
• [Presentation] Characteristics of Epithelial cell attachment to zirconia similar to titanium
  • Author(s): Ishihara Y, Okabe E, Sasaki K, Kobayashi S, Mizutani H, Izawa A, Goto H, Murakami H, Ban S, Kawai T, Noguchi T
  • Organizer: the 2nd Meeting of the International Association for Dental Research Asia Pacific Region
  • Place of Presentation: Bangkok
• [Presentation] A.actinomycetemcomitans菌刺激したIL-1Ra欠損マウス由来骨芽細胞の造骨系骨関連遺伝子発現
  • Author(s): 伊澤 有郎，石原裕一，水谷大樹，小林周一郎，小澤佑介，神谷洋介，久保勝俊，杉田好彦，前田初彦，野口俊英
  • Organizer: 第55回春季日本歯周病学会
  • Place of Presentation: 札幌
• [Presentation] 歯周炎患者における末梢血血清中のsIL-1RAcPと臨床所見との関係
  • Author(s): 水谷大樹，石原裕一，伊澤有郎，小澤佑介，相野 誠，亀井英彦，三谷章雄，林潤一郎，稲垣幸司，福田光男，野口俊英
  • Organizer: 第55回春季日本歯周病学会
  • Place of Presentation: 札幌
• [Presentation] IL-1RaKOマウスにおける骨代謝の低下
  • Author(s): 伊澤 有郎，石原裕一，水谷大樹，小林周一郎，小澤佑介，神谷洋介，久保勝俊，杉田好彦，前田初彦，野口俊英
  • Organizer: 第80回愛知学院大学歯学会学術大会
  • Place of Presentation: 名古屋