Role of leukotriene B4 and effector T cells in allergen-induced airway responses

2008 Fiscal Year Final Research Report

• Project/Area Number: 19599015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Okayama University
• Principal Investigator: MIYAHARA Nobuaki Okayama University, 医学部・歯学部附属病院, 助教 (70335610)
• Co-Investigator(Kenkyū-buntansha): KANEHIRO Arihiko 岡山大学, 医学部・歯学部附属病院, 講師 (20243503)
• Research Collaborator: GELFAND Md, ERWIN, W. National Jewish Medical and Research Center, Denver, CO,USA, Division of Cell Biology, Department of Pediatrics, Professfor and Chairman
• Project Period (FY): 2007 – 2008
• Keywords: 気管支喘息 / ロイコトリエン / LTB4-BLT1-肥満細胞 / リンパ球 / T細胞 / サイトカイン / 気道過敏性

Research Abstract

ロイコトリエンB4(LTB4)は、アラキドン酸に由来する 生理活性脂質であり、様々な炎症性疾患における重要な役割が示唆されてきた。LTB4がアレルギー性の気道反応に必須であるかどうかを直接証明するために、LTB4を全く産生しないLTA4 hydrolase knock out(LTA4HKO) マウスを用いて喘息モデルを作成し、コントロールの野生型マウスとの比較検討をおこなった。野生型マウスに比べ、LTA4HKOマウスは有意に低い気道過敏性を示し、肺内の好酸球の数、杯細胞の過形成の程度も低下していたことより、LTB4はアレルギー性気道反応においても反応惹起に必須であることが示唆された

Research Products

• [Journal Article] Gelfand EW Mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (2009)
  • Author(s): Ohnishi H, Takeda K, Domenico J, Lucas JJ, Miyahara N, Swasy CH, Dakhama A
  • Journal Title: 1/2-dependent pathways are essential for CD8+ T cell-mediated airway hyperresponsiveness and inflammation. J Allergy Clin Immunol 123 Pages: 249-57
  • Peer Reviewed
• [Journal Article] EW. Leukotriene B4 receptor-1 (BLT1) expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway (2008)
  • Author(s): Miyahara N, Ohnishi H, Matsuda H, Miyahara S, Takeda K, Koya T, Matsubara S, Okamoto M, Dakhama A, Haribabu B, Gelfand EW
  • Journal Title: hyperresponsiveness.J. Jmmunol 181 Pages: 1170-8
  • Peer Reviewed
• [Journal Article] Evidence That CD8+ Dendritic Cells Enable the Development of {gamma}{delta} T Cells That Modulate Airway (2008)
  • Author(s): Cook L, Miyahara N, Jin N, Wands JM, Taube C, Roark CL, Potter TA, Gelfand EW, O'Brien RL, Born WK
  • Journal Title: Hyperresponsiveness. J Immunol 181 Pages: 309-19
  • Peer Reviewed
• [Journal Article] アレルギー性気道炎症における樹状細胞および脂質メデイエーターの役割の検討 (2007)
  • Author(s): 宮原信明
  • Journal Title: アレルギア 36 Pages: 65-67
• [Journal Article] Leukotriene B4 Release from Mast Cells in IgE-Mediated Airway
  • Author(s): Miyahara N, Ohnishi H, Miyahara S, Takeda K, Matsubara S, Matsuda H, Okamoto M, Loader JE, Joetham A, Tanimoto M, Dakhama A, Gelfand EW
  • Journal Title: Hyperresponsiveness and Inflammation. Am J Respir Cell Mol Biol (in press)
  • Peer Reviewed
• [Presentation] Confirmation of the Essential Role of Leukotriene B4 in the Development of Airway Hyperresponsiveness Using Leukotriene A4 Hydrolase-Deficient Mice (2008)
  • Author(s): N. Miyahara
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-27
• [Presentation] Requirement for Leukotriene B4 Release from Mast Cells in the Development of IgE-Mediated Airway Hyperresponsiveness (2008)
  • Author(s): N. Miyahara
  • Organizer: Hyperresponsiveness, 104th Annual Meeting of American Thoracic Society
  • Place of Presentation: Totonto, Canada
  • Year and Date: 2008-05-18
• [Presentation] 樹状細胞およびロイコトリエンB4受容体のアレルギー性気道反応における役割の検討 (2007)
  • Author(s): 宮原信明, 他13名
  • Organizer: 日本アレルギー学会秋季学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-11-01
• [Presentation] CD8T細胞およびロイコトリエンB4受容体の気道過敏性における役割の検討 (2007)
  • Author(s): 宮原信明, 他9名
  • Organizer: 日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-06-11
• [Presentation] Requirement for the Leukotriene B4 Receptor-1 (BLT1) on Dendritic Cells in the Development of Allergen-Induced Airway Hyperresponsiveness (2007)
  • Author(s): N. Miyahara
  • Organizer: 103th Annual Meeting of American Thoracic Society
  • Place of Presentation: San Francisco
  • Year and Date: 2007-05-22
• [Presentation] Miyahara. Memory CD8+ T Cell-Mediated Airway Hyperresponsiveness and Allergic Airway Inflammation by Upregulating the Leukotriene B4 Receptor, BLT1 (2007)
  • Author(s): H. Ohnishi, N. Miyahara
  • Organizer: 103th Annual Meeting of American Thoracic Society
  • Place of Presentation: San Francisco
  • Year and Date: 2007-05-20
• [Book] Allergy frontiers : Classification and Pathomechanisms (2009)
  • Author(s): Miyahara N, Gelfand EW
  • Total Pages: 167-178
  • Publisher: Springer