Interaction of arachidonic acid metabolites and bioactive substances in formation of Th2 environment

• Project/Area Number: 24591553
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Saga University
• Principal Investigator: HAMASAKI yuhei 佐賀大学, 医学部, 客員研究員 (10172967)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Th2 / arachidonic acid / IL-33 / TRPA1 / アラキドン酸代謝物 / Th2サイトカイン / 温度感受性受容体 / ケラチノサイト / 気道上皮 / TRPV1 / INFｒ / TNFa / ケラチナサイト / サイトカイン / アラキドン酸

Outline of Final Research Achievements

We investigated an interaction between various bioactive substances and humen bronchial and skin epithelial cells. We found that (1) human bronchial epithelial cells constantly express TRPA1 and TRPV1 which are enhanced by poly IC stimulation,and(2) allyl-isothiocynanate, an agonist of TRPA1, stimulates production of IL-6 through pre-treatment of cells with poly IC. We also found that (3)the production of IL-33 is enhanced by TNFa and INFr in keratinocytes, human skin epithelial cells, and (4)anti-IL-33 antibody completely inhibits allergen induced-dermatitis in mice. These results indicate that TRPA1 is associated with airway inflammation induced by viral upper respiratory infection. Keratinocyte produced-IL-33 plays an important role in allergic inflammation in human skin diseases and IL-33 probably an important target for treatment and management of allergic diseases.

Research Products

• [Journal Article] Periostin controls keratinocyte proliferation and differentiation by interacting with the paracrine IL-1a/IL-6 loop. (2014)
  • Author(s): Taniguchi K, Arima K, Masuoka M, Ohta S, Shiraishi H, Ontsuka K, Suzuki S, Inamitsu M, Yamamoto K-i, Simmons O, Toda S, Conway SJ, Hamasaki Y, Izuhara K.
  • Journal Title: J Invest Dermatol Volume: 134 Issue: 5 Pages: 1295-1304
  • DOI: 10.1038/jid.2013.500
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Japanese Guideline for Childhood Asthma 2014 (2014)
  • Author(s): Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, Nishimuta T, Morikawa A
  • Journal Title: Allergol Int Volume: 63 Pages: 335-356
  • NAID: 130004687709
  • Peer Reviewed
• [Journal Article] Interleuleukin 33 is induced by tumor necrosis factor  and interferon  in keratinocytes and contributes and contributes to allergic contact dermatitis (2013)
  • Author(s): Taniguchi K, Yamamoto S, Hitomi E, Inada Y, Suyama Y, Sugioka T, Hamasaki Y
  • Journal Title: J Investig Allergol Clin Immunol. Volume: 23(6) Pages: 428-434
  • Peer Reviewed
• [Journal Article] 小児喘息の長期管理におけるロイコトリエン受容体拮抗薬(LTRA)の役割 (2012)
  • Author(s): 浜崎雄平，山本修一，在津正文
  • Journal Title: 日本小児アレルギー学会誌 Volume: 26 Pages: 85-95
  • NAID: 10030557300
  • Peer Reviewed
• [Presentation] The IL-1 alpha/periostin/IL-6 axis contributes to the keratinocyte proliferation and differentiation in atopic dermatitis (2012)
  • Author(s): K Taniguchi, K Arima, M Masuoka, H Shiraishi, K Ontsuka, S Suzuki, T Sugioka, Y Hamasaki, K Izuhara
  • Organizer: 29th Symposium of Collegium Internationale Allergologicum
  • Place of Presentation: Korea