The role of interleukin-6 epigenetics in the pathogenesis of periodontitis and rheumatoid arthritis

• Project/Area Number: 22390396
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Niigata University
• Principal Investigator: YOSHIE Hiromasa 新潟大学, 医歯学系, 教授 (20143787)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Tetsuo 新潟大学, 医歯学総合病院, 准教授 (00215344) ; KUBOTA Takehiko 新潟大学, 医歯学総合病院, 講師 (50303136) ; KOMATSU Yasutaka 新潟大学, 医歯学総合病院, 助教 (40422597)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2010: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 歯周炎 / リウマチ / IL-6 / エピジェネティクス / ｴﾋﾟｼﾞｪﾈﾃｨｸｽ / インターロイキン6 / ゲノム

Research Abstract

The aim of this study was to elucidate the role of interleukin-6 gene methylation in the pathogenesis of periodontitis and rheumatoid arthritis. The results indicated that the gene contained 19 methylation motifs, and hypomethylated status of a single motif was associated with two diseases. Additionally, methylation level was decreased in the gingival than those in blood, suggesting an increased level of IL-6 gene activity and inflammatory condition.

Research Products

• [Journal Article] Assessment of Interleukin-6 Receptor Inhibition Therapy on Periodontal Condition in Patients with Rheumatoid Arthritis and Chronic Periodontitis (2013)
  • Author(s): Kobayashi T, Okada M, Ito S, Kobayashi D, Ishida K, Kojima A, Narita I, Murasawa A, Yoshie H
  • Journal Title: J. Periodontol Volume: (in press) Issue: 1 Pages: 57-67
  • DOI: 10.1902/jop.2013.120696
  • Peer Reviewed
• [Journal Article] Interleukin-6 gene promoter methylation in rheumatoid arthritis and chronic periodontitis (2012)
  • Author(s): Ishida K, Kobayashi T, Ito S, Komatsu Y, Yokoyama T, Okada M, Abe A, Murasawa A, Yoshie H
  • Journal Title: J Periodontol Volume: 83(7) Issue: 7 Pages: 917-925
  • DOI: 10.1902/jop.2011.110356
  • Peer Reviewed
• [Journal Article] Association of the FcγRIIB-nt645+25A/G polymorphism with the expression level of the FcγRIIb receptor, the antibody response to Porphyromonas gingivalis and the severity of periodontitis (2012)
  • Author(s): Sugita N, Iwanaga R, Kobayashi T, Yoshie H
  • Journal Title: J Periodont Res Volume: 47(1) Issue: 1 Pages: 105-113
  • DOI: 10.1111/j.1600-0765.2011.01411.x
  • Peer Reviewed
• [Journal Article] 歯周炎と関節リウマチ-関連性と臨床対応- (2012)
  • Author(s): 小林哲夫、吉江弘正
  • Journal Title: 日本歯周病学会会誌 Volume: 54巻1号 Pages: 11-17
  • NAID: 10030555150
  • Peer Reviewed
• [Journal Article] Characterization of human-type monoclonal antibod es against reduced form of hemin binding protein 35 from Porphyromonas gingivalis. (2011)
  • Author(s): Shibata Y, Okano S, Shiroza T, Tahara T, Nakazawa K, Kataoka S, Ishida I, Kobayashi T, Yoshie H, Abiko Y
  • Journal Title: J Periodontal Res. Volume: Vol46 Issue: 6 Pages: 673-81
  • DOI: 10.1111/j.1600-0765.2011.01389.x
  • Peer Reviewed
• [Journal Article] Antibody responses to periodontopathic bacteria in relation to rheumatoid arthritis in Japanese adults (2011)
  • Author(s): Okada M, Kobayashi T, Ito S, Yokoyama T, Komatsu Y, Abe A, Murasawa A, Yoshie H
  • Journal Title: J.Periodontol Volume: 82(10) Issue: 10 Pages: 1433-1441
  • DOI: 10.1902/jop.2011.110020
  • Peer Reviewed
• [Journal Article] Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues (2011)
  • Author(s): Abe D, Kubota T, Morozumi T, Shimizu T, Nakasone N, Itagaki M, Yoshie H
  • Journal Title: J Periodontal Res Volume: 46 Issue: 3 Pages: 345-353
  • DOI: 10.1111/j.1600-0765.2011.01349.x
  • Peer Reviewed
• [Journal Article] Proteomic profiling of human neutrophils in relation to immunoglobulin G Fc receptor IIIB polymorphism (2010)
  • Author(s): Yokoyama T, Kobayashi T, Yamamoto K, Yamagata A, Oofusa K, Yoshie H
  • Journal Title: J Periodont Res Volume: 45(6) Issue: 6 Pages: 780-787
  • DOI: 10.1111/j.1600-0765.2010.01300.x
  • Peer Reviewed
• [Journal Article] Serum cytokine and periodontal profiles in relation to disease activity of rheumatoid arthritis in Japanese adults (2010)
  • Author(s): Kobayashi T, Murasawa A, Komatsu Y, Yokoyama T, Yamamoto K, Ishida K, Abe A, Yamamoto K, Yoshie H
  • Journal Title: J. Periodontol Volume: 81(5) Issue: 5 Pages: 650-657
  • DOI: 10.1902/jop.2010.090688
  • Peer Reviewed
• [Journal Article] Serum cytokine and periodontal profiles in relation to disease activity of rheumatoid arthritis in Japanese adults (2010)
  • Author(s): Tetsuo Kobayashi
  • Journal Title: Journal of Periodontology Volume: VOL.81 Pages: 650-657
  • Peer Reviewed
• [Presentation] Effects of Anti-Tumor Necrosis Factor Therapy on Periodontal Condition in Patients with Rheumatoid Arthritis (2012)
  • Author(s): Kobayashi T
  • Organizer: The 52nd. Annual Scientific Meeting of the Korean Academy of Periodontology
  • Place of Presentation: Seoul, Korea.
  • Year and Date: 2012-11-24
• [Presentation] Improvement of the Activity of Rheumatoid Arthritis by Periodontal Therapy (2012)
  • Author(s): Okada M
  • Organizer: The 52nd. Annual Scientific Meeting of the Korean Academy of Periodontology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-11-24
• [Presentation] 歯周炎罹患歯肉におけるIL-6遺伝子プロモーター領域のメチル化解析 (2012)
  • Author(s): 石田光平
  • Organizer: 日本歯科保存学会2012年度秋季学術大会(第137回)
  • Place of Presentation: 広島
  • Year and Date: 2012-11-22
• [Presentation] 関節リウマチおよび歯周炎の関連血清タンパク質のプロテオーム解析 (2012)
  • Author(s): 横山智子
  • Organizer: 第55回秋季日本歯周病学会学術大会
  • Place of Presentation: 筑波
  • Year and Date: 2012-09-23
• [Presentation] 関節リウマチおよび慢性歯周炎患者における血漿アミノ酸解析 (2012)
  • Author(s): 岡田萌
  • Organizer: 第55回秋季日本歯周病学会学術大会
  • Place of Presentation: 筑波
  • Year and Date: 2012-09-23
• [Presentation] Improvement of periodontal condition by anti-tumor necrosis factor therapy in rheumatoid arthritis patients (2012)
  • Author(s): Kobayashi T
  • Organizer: EuroPerio 7
  • Place of Presentation: Vienna, Austria.
  • Year and Date: 2012-06-07
• [Presentation] Effects of periodontal therapy on the condition of rheumatoid arthritis (2012)
  • Author(s): Okada M
  • Organizer: EuroPerio 7
  • Place of Presentation: Vienna, Austria.
  • Year and Date: 2012-06-07
• [Presentation] 抗TNF療法による関節リウマチ患者の歯周組織状態の改善 (2012)
  • Author(s): 小林哲夫
  • Organizer: 第55回春季日本歯周病学会学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2012-05-18
• [Presentation] 歯周治療による関節リウマチへの影響 (2012)
  • Author(s): 岡田萌
  • Organizer: 第55回春季日本歯周病学会学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2012-05-18
• [Presentation] 抗TNF療法による関節リウマチ患者の歯周組織状態への影響 (2012)
  • Author(s): 小林哲夫
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-26
• [Presentation] Proteomic profiling of human serum in relation to rheumatoid arthritis and periodontitis (2012)
  • Author(s): Yokoyama T
  • Organizer: The 98th. Annual Meeting of the American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Los Angels, USA.
• [Presentation] 関節リウマチおよび歯周炎患者におけるIL-6遺伝子プロモーター領域のメチル化解析 (2011)
  • Author(s): 石田光平
  • Organizer: 第54回秋季日本歯周病学会学術大会
  • Place of Presentation: 下関.
  • Year and Date: 2011-09-24
• [Presentation] 関節リウマチおよび歯周炎患者におけるIL-6遺伝子プロモーター領域のメチル化解析 (2011)
  • Author(s): 石田光平
  • Organizer: 第54回秋季日本歯周病学会学術大会
  • Place of Presentation: 海峡メッセ(山口県下関市)
  • Year and Date: 2011-09-24
• [Presentation] TACE及びTIMP-3の薬物性歯肉増殖症と歯周炎の歯肉組織における遺伝子発現とタンパク質局在 (2011)
  • Author(s): 冨田尊志
  • Organizer: 第54回秋季日本歯周病学会学術大会
  • Place of Presentation: 海峡メッセ(山口県下関市)
  • Year and Date: 2011-09-24
• [Presentation] 関節リウマチにおける歯周炎関連タンパク質の網羅的解析 (2011)
  • Author(s): 小林哲夫
  • Organizer: 日本歯科保存学会2011年度春季学術大会(第134回)
  • Place of Presentation: 浦安
  • Year and Date: 2011-06-09
• [Presentation] 歯周炎関連血清タンパク質のプロテオーム解析 (2011)
  • Author(s): 横山智子
  • Organizer: 日本歯科保存学会2011年度春季学術大会(第134回)
  • Place of Presentation: 浦安
  • Year and Date: 2011-06-09
• [Presentation] 歯周病原細菌に対する血清抗体価と関節リウマチとの関連 (2011)
  • Author(s): 岡田萌
  • Organizer: 日本歯科保存学会2011年度春季学術大会(第134回)
  • Place of Presentation: 浦安
  • Year and Date: 2011-06-09
• [Presentation] I nterleukin-6 gene promoter methylation in relation to rheumatoid arthritis and periodontitis (2011)
  • Author(s): Ishida K
  • Organizer: The 97th. Annual Meeting of the American Academy of Periodontology
  • Place of Presentation: Miami, USA.
• [Presentation] Serum cytokine and periodontal profiles related to rheumatoid arthritis activity (2010)
  • Author(s): Kobayashi T
  • Organizer: The 96th. Annual Meeting of the American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Honolulu, USA.
  • Year and Date: 2010-11-01
• [Presentation] Genetic influence of serum interleukin-6 and its soluble receptor levels (2010)
  • Author(s): Komatsu Y
  • Organizer: The 96th. Annual Meeting of the American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Honolulu, USA.
  • Year and Date: 2010-11-01
• [Presentation] DNA methylation status of the interleukin-6 gene promoter in periodontitis (2010)
  • Author(s): Ishida K
  • Organizer: The 96th. Annual Meeting of the American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Honolulu, USA.
  • Year and Date: 2010-11-01
• [Presentation] 歯周炎および関節リウマチ患者におけるIL-6遺伝子プロモーター領域のメチル化解析 (2010)
  • Author(s): 石田光平
  • Organizer: 第53回秋季日本歯周病学会学術大会
  • Place of Presentation: 高松
  • Year and Date: 2010-09-19
• [Presentation] 歯周炎および関節リウマチ患者におけるIL-6遺伝子プロモーター領域のメチル化解析 (2010)
  • Author(s): 石田光平
  • Organizer: 第53回秋季日本歯周病学会学術大会
  • Place of Presentation: サンポートホール高松(香川県高松市)
  • Year and Date: 2010-09-19
• [Presentation] 歯周炎罹患歯肉におけるIL-6遺伝子プロモーター領域のメチル化解析
  • Author(s): 石田光平
  • Organizer: 日本歯科保存学会2012年度秋季学術大会（第137回）
  • Place of Presentation: 広島国際会議場（広島県広島市）
• [Book] イラストで語る歯科医学最前線 (2013)
  • Author(s): 小林哲夫、吉江弘正
  • Publisher: クインテッセンス出版
• [Book] AT THE FOREFRONT. Illustrated Topics in Dental Research and Clinical Practice (2012)
  • Author(s): Tetsuo Kobayashi、Hiromasa Yoshie
  • Publisher: Quintessence Publishing Co, Inc
• [Remarks]
  • URL: http://mds.niigata-u.ac.jp/organization/ols/obs/per/index_j.html
• [Remarks]
  • URL: http://mds.niigata-u.ac.jp/organization/ols/obs/per/indexj.html