The structure based drug design for controlling the innate immune response and interleukin-18 signaling.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20790723
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: OHNISHI Hidenori Gifu University, 医学部附属病院, 助教 (60381620)
• Project Period (FY): 2008 – 2010
• Keywords: 自然免疫 / IL-18 / Toll-like receptor / MyD88 / タンパク立体構造

Research Abstract

MyD88 is the important adaptor molecule in the Toll like receptors and IL-1/18 signaling pathways. In this study, we tried to create the molecule, which regulate these immune signaling response, based on the results of our decided protein structure of MyD88 and protein interaction studies. In the duration of this research aid, we could develop the several methods of direct protein-protein interaction studies with the TIR domain containing molecules. Furthermore, we created the new molecule, protein transduction domain containing dominant negative formed MyD88 (PTD-MyD88-DN). We will continue the drug development that assumed MyD88 a target.

Research Products

• [Journal Article] Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis. (2011)
  • Author(s): An Y, Ohnishi H, Matsui E, Funato M, Kato Z, Teramoto T, Kaneko H, Kimura T, Kubota K, Kasahara K, Kondo N.
  • Journal Title: Int J Mol Med. 27(6) Pages: 795-801
  • Peer Reviewed
• [Journal Article] Antigen-specific immune response to endotoxin-free recombinant P34 (2011)
  • Author(s): Morita H, Kaneko H, Ohnishi H, Kato Z, Kondo N.
  • Journal Title: .Allergy.
  • Peer Reviewed
• [Journal Article] Efficacy of the slow dose-up method for specific oral tolerance induction in children with cow's milk allergy : comparison with reported protocols. (2010)
  • Author(s): Kaneko H, Teramoto T, Kondo M, Morita H, Ohnishi H, Orii K, Matsui E, Kondo N.
  • Journal Title: J Investig Allergol Clin Immunol. 20(6) Pages: 538-539
  • Peer Reviewed
• [Journal Article] Mutation in the Q28SDD31SD site, but not in the two SQ sites of the survival of motor neuron protein, affects its foci formation. (2010)
  • Author(s): Aoki Y, Fukao T, Zhang G, Ohnishi H, Kondo N.
  • Journal Title: Int J Mol Med. 26(5) Pages: 667-671
  • Peer Reviewed
• [Journal Article] Interleukin-17 expression in the urticarial rash of familial cold autoinflammatory syndrome : a case report. (2010)
  • Author(s): Yamauchi A, Iwata H, Ohnishi H, Teramoto T, Kondo N, Seishima M.
  • Journal Title: Br J Dermatol. 163(6) Pages: 1351-1353
  • Peer Reviewed
• [Journal Article] 1H, 13C, and 15N resonance assignment of the TIR domain of human MyD88. (2010)
  • Author(s): Ohnishi H, Tochio H, Kato Z, Kimura T, Hiroaki H, Kondo N, Shirakawa M.
  • Journal Title: Biomol NMR Assign. 4(2) Pages: 123-125
  • Peer Reviewed
• [Journal Article] Prediction of the pathogenesis of the mutation in MeCP2 C-terminal domain. (2010)
  • Author(s): Kato Z, Ohnishi H, Kimura T, Kondo N.
  • Journal Title: Brain Dev. 32(2) Pages: 169
  • Peer Reviewed
• [Journal Article] Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling. (2009)
  • Author(s): Ohnishi H, Tochio H, Kato Z, Orii KE, Li A, Kimura T, Hiroaki H, Kondo N, Shirakawa M.
  • Journal Title: Proc Natl Acad Sci USA. 106(25) Pages: 10260-10265
  • Peer Reviewed
• [Journal Article] Expression, purification and structural analysis of human IL-18 binding protein : a potent therapeutic molecule for allergy. (2008)
  • Author(s): Kimura T, Kato Z, Ohnishi H, Tochio H, Shirakawa M, Kondo N.
  • Journal Title: Allergol Int. 57(4) Pages: 367-376
  • Peer Reviewed
• [Journal Article] Hypothermia augments NF-kappaB activity and the production of IL-12 and IFN-gamma. (2008)
  • Author(s): Arai T, Kaneko H, Ohnishi H, Matsui E, Fukao T, Kawamoto N, Kasahara K, Kondo N.
  • Journal Title: Allergol Int. 57(4) Pages: 331-338
  • Peer Reviewed
• [Journal Article] A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma. (2008)
  • Author(s): Bai C, Matsui E, Ohnishi H, Kimata K, Kasahara K, Kaneko H, Kato Z, Fukao T, Kondo N.
  • Journal Title: Int J Mol Med. 21(2) Pages: 139-144
  • Peer Reviewed
• [Presentation] 自然免疫異常症、アレルギー疾患病態解明に向けたプロテオミクス的手法の応用 (2010)
  • Author(s): 大西秀典、加藤善一郎、木村豪、安陽、久保田一生、松井永子、金子英雄、近藤直実
  • Organizer: 第47回日本小児アレルギー学会
  • Place of Presentation: 横浜
  • Year and Date: 20101204-20101205
• [Presentation] Structural basis for the innate immune deficiency syndrome. (2010)
  • Author(s): Hidenori Ohnishi, Hidehito Tochio, Zenichiro Kato, Takeshi Kimura, Masatoshi Nada, Kazuo Kubota, Masahiro Shirakawa, Naomi Kondo.
  • Organizer: The 8th Asia Pacific Congress of Allergy, Asthma and Clinical Immunology 2010.
  • Place of Presentation: Singapore.
  • Year and Date: 20101106-20101109
• [Presentation] The LPS induced enhancement of IL-1β and IL-18 production is a useful tool for diagnosis of familial cold inflammatory syndrome (FCAS). (2010)
  • Author(s): Hidenori Ohnishi, Takahide Teramoto, Zenichiro Kato, Hideo Kaneko, Ryuta Nishikomori, Naomi Kondo.
  • Organizer: Autoinflammation 2010.
  • Place of Presentation: Amsterdam, Netherlands.
  • Year and Date: 20100902-20100906
• [Presentation] A conserved interaction mode between MyD88 and distinct membrane-sorting adaptors in TLR4 and IL-18 signaling. (2010)
  • Author(s): H.Ohnishi, H.Tochio, Z.Kato, T.Kimura, T.Funasaka, R.W.Wong, M.Shirakawa, N.Kondo.
  • Organizer: 14th International Congress of Immunology.
  • Place of Presentation: Kobe.
  • Year and Date: 20100822-20100827
• [Presentation] Structural basis for the interactions of the MyD88 TIR domain in TLR4 signaling. (2010)
  • Author(s): Hidenori Ohnishi, Hidehito Tochio, ZenichiroKato, Takeshi Kimura, Naomi Kondo, Masahiro Shirakawa.
  • Organizer: World wide magnetic resonance conference 2010.
  • Place of Presentation: Florence, Italy.
  • Year and Date: 20100704-20100709
• [Presentation] The genetic variations of the MyD88 adaptor protein like (Mal) are associated with allergic diseases in Japanese population. (2010)
  • Author(s): Hidenori Ohnishi, Yang An, Eiko Matsui, Zenichiro Kato, Hideo Kaneko, Naomi Kondo.
  • Organizer: The 20th Interasma Japan/North Asia.
  • Place of Presentation: Tokyo.
  • Year and Date: 20100702-20100703
• [Presentation] 乳児栄養の役割:母乳・人工乳 (2010)
  • Author(s): 大西秀典、金子英雄、森田秀行、川本美奈子、松井永子、加藤善一郎、近藤直実
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 20100423-20100426
• [Presentation] アレルギー発症にかかわる分子の構造学的解明と臨床応用 (2008)
  • Author(s): 大西秀典, 加藤善一郎, 木村豪, 徳見哲史, 福富悌, 近藤直実
  • Organizer: 第45回日本小児アレルギー学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-14
• [Book] Genetics of Pediatric Asthma.(Allergy Frontiers (volumel Allergy Frontiers : Epigenetics, Allergens and Risk Factors))(Pawankar R, Holgate ST, Rosenwasser LJ eds.) (2009)
  • Author(s): Kondo N, Matsui E, Kaneko H, Fukao T, Teramoto T, Kato Z, Ohnishi H, Nishimura A
  • Total Pages: 442
• [Remarks] ホームページ等
• [Patent(Industrial Property Rights)] 変異導入MyD88蛋白によるToll様受容体/インターロイキン18シグナルの特異的制御法 (2008)
  • Inventor(s): 近藤直実、加藤善一郎、大西秀典、白川昌宏、杤尾豪人
  • Industrial Property Rights Holder: 岐阜大学、京都大学
  • Industrial Property Number: PCT/JP,2008/064170
  • Filing Date: 2008-07-31
  • Overseas