Grant-in-Aid for Specially Promoted Research.
|Research Institution||Osaka University|
KISHIMOTO Tadamitsu Osaka University, Medical School, Professor, 医学部, 教授 (10093402)
OGAWA Hiroyasu Medical Research Institute Medical School, Assistant Professor, 医学部, 講師 (80194447)
SAEKI Yukihiko Medical Research Institute Medical School, Assistant Professor, 医学部, 助手 (40240840)
TAGA Tetsuya Tokyo Medical and Dental University, Professor, 難治疾患研究所, 教授 (40192629)
審良 静男 大阪大学, 細胞生体工学センター, 助教授 (50192919)
|Project Fiscal Year
1993 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥240,000,000 (Direct Cost : ¥240,000,000)
Fiscal Year 1996 : ¥45,000,000 (Direct Cost : ¥45,000,000)
Fiscal Year 1995 : ¥50,000,000 (Direct Cost : ¥50,000,000)
Fiscal Year 1994 : ¥50,000,000 (Direct Cost : ¥50,000,000)
Fiscal Year 1993 : ¥95,000,000 (Direct Cost : ¥95,000,000)
|Keywords||gp130 / STAT3 / NF-IL6 / CD40 / HIV coreceptor / chemokine PBSF / SDF-1 / ケモカインPBSF / IL-6レセプター / STAT6 / ノックアウトマウス / キャッスルマン病 / リウマチ / サイトカイン / APRF / CD23 / SCIDマウス / 自己免疫病 / サイトカインシグナル伝達|
Representative results which have been obtained by the studies done between 1993-1996 under the support by the Grant-in-Aid for Specially Promoted Research are as follows ;
i) Outline of the signal transduction through IL-6 receptor and gp130 has been elucidated, i.e.two signalling pathways have been identified, namely a) JAK-STAT3/APRF pathway and b) Ras-Map kinase cascade and activation of NF-IL6.
ii) Targetted disruption of the genes inyolved in the cytokine signalling revealed the hitherto unknown in vivo function of the signalling molecules such as gp130, STAT3, STAT6 and NF-IL6. NF-IL6 knockout mice were completely sensitive to Listeria infection, revealing the essential role of NF-IL6 in bactericidal activity of macrophage. gp130 knockout was lethal and cardiac muscle development was impared, revealing the essential role of the signals through gp130 for cardiac muscle development and prevention of apoptosis.
iii) A chemokine (PBSF/SDF-1) and its receptor which are one of the essential factor for pre B cell development, have been cloned and the results have revealed that a receptor for PBSF/SDF-1 functions as a HIV coreceptor, fusin.
iv) The genes encoding coreceptors for B lymphocyte activation, CD40 and CD23 have been knocked out and in vivo roles of these molecules in humoral and T cell-dependent cellular immunity are revealed.
v) Experimental treatments of patients with multiple myeloma, Castleman's disease and rheumatoid arthritis with humanized anti-IL6 receptor antibody have been carried out and its effectiveness on these diseases are confirmed.
6)TGF-β、 PDGF-B、 IL6-IL6R遺伝子をラット肺上皮細胞に移入し、発現させ、種々の間質性肺炎(IPF、 ILP等)の発症誘導に成功。