The effect of EGF receptor pathway on cytokine production in gingival fibroblasts

• Project/Area Number: 23593077
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Himeji Dokkyo University
• Principal Investigator: KOGOE Nahoko 姫路獨協大学, 薬学部, 助手 (60509115)
• Co-Investigator(Kenkyū-buntansha): OHYAMA Hideki 兵庫医科大学, 医学部, 准教授 (90280685) ; KURODA Yoshihiro 姫路獨協大学, 薬学部, 教授 (90093236)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: EGFR / 歯肉線維芽細胞 / 歯肉上皮細胞 / CCL17 / CCL22 / 歯周病 / ＢＡＦＦ / ＡＰＲＩＬ

Research Abstract

This study focused on the effects of EGF-R pathway on the productivity of chemokines and cytokines in gingival fibroblasts and gingival epithelial cells. We found that inhibition of EGF-R signaling leads to the expression of BAFF, APRIL, and TSLP that is cytokines help to shape the local accumulation and activation of Th2 responses and B cell immunoglobulin production. In addition, EGF-R signaling blockade produces the effect with increased Th2 chemokines, CCL11, CCL17, and CCL26 expression, although no effect with Th1 chemokines, CXCL9, CXCL10, and CXCL11 expression in gingival fibroblasts. These results may imply additional mechanisms by which EGF-R pathway the immune responses in periodontal lesion.

Research Products

• [Journal Article] Oligopeptides derived from autophosphorylation sites of EGF receptor suppress EGF-stimulated responses in human lung carcinoma A549 cells. (2013)
  • Author(s): Kuroda Y, Kato-Kogoe N, Tasaki E, Murata M, Ueda K, Abe M, Miyamoto K, Nakase I, Futaki S, Tohyama Y, Hirose M
  • Journal Title: Eur J Pharmacol Volume: 698 Issue: 1-3 Pages: 87-94
  • DOI: 10.1016/j.ejphar.2012.10.007
  • Peer Reviewed
• [Journal Article] T-cell Responses Involved in the Predisposition to Periodontal Disease: Lessons from Immunogenetic Studies of Leprosy (2013)
  • Author(s): Hideki Ohyama, Nahoko Kato-Kogoe, Kazu Takeuchi-Hatanaka, Koji Yamanegi, Naoko Yamada, Keiji Nakasho, Sho Matsushita and Nobuyuki Terada
  • Journal Title: J Clin Cell Immunol Volume: S1 Pages: 1-7
  • DOI: 10.4172/2155-9899.s1-005
  • Peer Reviewed
• [Journal Article] The promotional effect of IL-22 on mineralization activity of periodontal ligament cells (2012)
  • Author(s): Kato-Kogoe N, Nishioka T, Kawabe M, Kataoka F, Yamanegi K, Yamada N, Hata M, Yamamoto T, Nakasho K, Urade M, Terada N, Ohyama H
  • Journal Title: Cytokine Volume: 59(1) Issue: 1 Pages: 41-8
  • DOI: 10.1016/j.cyto.2012.03.024
  • Peer Reviewed
• [Journal Article] Effects of TrkA inhibitory peptide on cancer-induced pain in a mouse melanoma model. (2012)
  • Author(s): Tabata M, Murata E, Ueda K, Kato-Kogoe N, Kuroda Y, Hirose M
  • Journal Title: J Anesth Volume: 26 Issue: 4 Pages: 545-551
  • DOI: 10.1007/s00540-012-1377-7
  • NAID: 10031070301
  • Peer Reviewed
• [Journal Article] Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma (2012)
  • Author(s): Yamanegi K, Yamane J, Kobayashi K, Kato-Kogoe N, Ohyama H, Nakasho K, YamadaN, Hata M, Fukunaga S, Futani H, Okamura H, Terada N.
  • Journal Title: cells to Fas- and NK cell-mediated cell death.Int J Oncol. Volume: 41(1) Pages: 83-91
  • DOI: 10.3892/ijo.2012.1438
  • Peer Reviewed
• [Journal Article] The promotional effect of IL-22 on mineralization activity of periodontal ligament cells. (2012)
  • Author(s): Kato-Kogoe N, Nishioka T, Kawabe M, Kataoka F, Yamanegi K, Yamada N, Hata M, Yamamoto T, Nakasho K, Urade M, Terada N, Ohyama H.
  • Journal Title: Cytokine. Volume: Apr 24
  • Peer Reviewed
• [Journal Article] Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death. (2012)
  • Author(s): Yamanegi K, Yamane J, Kobayashi K, Kato-Kogoe N, Ohyama H, Nakasho K, Yamada N, Hata M, Fukunaga S, Futani H, Okamura H, Terada N.
  • Journal Title: Int J Oncol. Volume: in press
  • Peer Reviewed
• [Journal Article] Effects of TrkA inhibitory peptide on cancer-induced pain in a mouse melanoma model. (2012)
  • Author(s): Tabata M, Murata E, Ueda K, Kato-Kogoe N, Kuroda Y, Hirose M.
  • Journal Title: J Anesth. Volume: in press
  • NAID: 10031070301
  • Peer Reviewed
• [Presentation] IGF-1Rの自己リン酸化部位由来ペプチドがMCF-7ヒト乳がん細胞に及ぼす影響 (2013)
  • Author(s): 黒田義弘,小越菜保子,田崎絵美,中瀬生彦,二木史朗,通山由美,廣瀬宗孝
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-09-11
• [Presentation] EGFRの自己リン酸化部位由来ペプチドのA549ヒト肺腺がん細胞における効果 (2011)
  • Author(s): 黒田義弘,村田恵理,上田康陽,田崎絵美,小越菜保子,阿部峰大,宮本和英,中瀬生彦,二木史朗,通山由美,廣瀬宗孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] IL‐22存在下においてヒト歯根膜由来細胞が発現する遺伝子の網羅的解析 (2011)
  • Author(s): 川辺睦記,大山秀樹,安川陽子,小越菜保子,安孫子宜光
  • Organizer: 第54回日本歯周病学会春季学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2011-05-28
• [Presentation] EGFRの自己リン酸化部位由来ペプチドの A549ヒト肺腺がん細胞における効果 (2011)
  • Author(s): 黒田義弘，村田恵理，上田康陽，田崎絵美，小越菜保子，阿部峰大，宮本和英，中瀬生彦，二木史朗，通山由美，廣瀬宗孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] IL-22がヒト歯根膜由来細胞の石灰化ノジュール形成に及ぼす影響 (2011)
  • Author(s): 大山 秀樹，小越 菜保子，川辺 睦記，安川 陽子，安孫子 宜光
  • Organizer: 第54回春季日本歯周病学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] IL-22存在下においてヒト歯根膜由来細胞が発現する遺伝子の網羅的解析 (2011)
  • Author(s): 川辺睦記，大山秀樹，安川陽子，小越菜保子，安孫子宜光
  • Organizer: 第54回春季日本歯周病学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] IGF-1Rの自己リン酸化部位由来ペプチドがMCF-7ヒト乳がん細胞に及ぼす影響
  • Author(s): 黒田 義弘
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜