The effect of calprotectin on mechanism of progression of diabetes-associated periodontitis

• Project/Area Number: 15K20621
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Periodontology
• Research Institution: The University of Tokushima
• Principal Investigator: IKUTA Takahisa 徳島大学, 病院, 医員 (00746563)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: カルプロテクチン / 糖尿病関連歯周炎 / TLR4 / IL-6 / THP-1 / sIL-6R / ヒト歯肉繊維芽細胞 / ヒト歯肉線維芽細胞

Outline of Final Research Achievements

Diabetic patients are susceptible to severe periodontitis, but the precise mechanism is not well understood. Purpose of this study was to investigate the biological pathogenesis of severe periodontitis in diabetic patients focusing on calprotectin (CPT) effects in human gingival fibroblasts (HGFs) and macrophages crosstalk.The results were as follows:1. CPT increased significantly IL-6 production via TLR4-NF-κB pathway in HGFs.2. High glucose increased significantly sIL-6R production via Tace activation in THP-1 macrophages.
These results support that diabetic conditions such as HG may induce sIL-6R production from macrophages and may exacerbate the periodontitis synergistically via CPT-induced IL-6 production in HGFs. CPT or HG-induced IL-6 cascades surrounding HGFs may lead in periodontitis progression through the crosstalk of fibroblasts-macrophages. This pathway could be an attractive target to clarify the pathogenesis of severe periodontitis in diabetic patients.

Research Products

• [Journal Article] Advanced glycation end-products increase IL-6 and ICAM-1 expression via RAGE, MAPK and NF-κB pathways in human gingival fibroblasts (2017)
  • Author(s): Nonaka K.、Kajiura Y.、Bando M.、Sakamoto E.、Inagaki Y.、Lew J. H.、Naruishi K.、Ikuta T.、Yoshida K.、Kobayashi T.、Yoshie H.、Nagata T.、Kido J.
  • Journal Title: Journal of Periodontal Research Volume: - Issue: 3 Pages: 1-11
  • DOI: 10.1111/jre.12518
  • NAID: 120006845647
  • Peer Reviewed
• [Journal Article] Clinical significance of GCF sIL-6R and calprotectin to evaluate the periodontal inflammation. (2017)
  • Author(s): Kajiura Y, Lew JH, Ikuta T, Nishikawa Y, Kido J, Nagata T, Naruishi K. ANNALS EXPRESS
  • Journal Title: Annals of Clinical Biochemistry Volume: 印刷中 Issue: 6 Pages: 1-7
  • DOI: 10.1177/0004563216680232
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ヒト口腔上皮細胞と歯肉線維芽細胞において低酸素環境が誘導する遺伝子発現の比較 (2015)
  • Author(s): 木戸淳一、板東美香、中島由紀子、梶浦由加里、稲垣裕司、生田貴久、坂本英次郎、成石浩司、永田俊彦
  • Organizer: 第143回秋季日本歯科保存学会
  • Place of Presentation: 文京ビックホール(東京都文京区）)
  • Year and Date: 2015-11-12
• [Presentation] 最終糖化産物は口腔上皮細胞の遺伝子発現を調節する (2015)
  • Author(s): 坂本英次郎、木戸淳一、梶浦由加里、板東美香、稲垣裕司、成石浩司、生田貴久、永田俊彦
  • Organizer: 第58回秋季日本歯周病学会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2015-09-12
• [Presentation] YKL-40 in gingival crevicular fliuid from patients with periodontitis and diabetes. (2015)
  • Author(s): Ikuta T, Kajiura Y, Bando Y, Bando M, Inagaki Y, Naruishi K, Kido J, Nagata T.
  • Organizer: Euro Perio 2015
  • Place of Presentation: London UK
  • Year and Date: 2015-06-03