Grant-in-Aid for international Scientific Research
|Allocation Type||Single-year Grants|
|Research Institution||University of Tokyo|
MATSUSHIMA Kouji University of Tokyo, Graduate School of Medicine, Department of Moleclar Preventive Medicine, Professor, 大学院医学系研究科, 教授 (50222427)
OPPENHEIM Joost.J. National Cancer Institute (USA), Laboratory of Molecular Immunoregulation, Chief, 研究室主任
HARADA Akihisa Kanazawa University, School of Medicine, Department of Hygiene, Research Associa, 医学部, 助手 (00228636)
KOBAYASHI Yoshiro Toho University, Faculty of Science, Professor, 理学部, 教授 (10134610)
KASAHARA Tadashi Koristu College of Pharmacy, Division of Biochemistry, Professor, 薬学部, 教授 (60049096)
MUKAIDA Naofumi Kanazawa University, Cancer Research Institute, Department of Molecular Pharmaco, がん研究所, 助教授 (30182067)
THESTRUPーPED クリスチ デンマーク王国Aarhus大学, 医学部, 教授
PEDERSEN Kri デンマーク王国Aarhus大学, 医学部, 教授
|Project Period (FY)
1996 – 1997
Completed(Fiscal Year 1997)
|Budget Amount *help
¥10,800,000 (Direct Cost : ¥10,800,000)
Fiscal Year 1997 : ¥5,400,000 (Direct Cost : ¥5,400,000)
Fiscal Year 1996 : ¥5,400,000 (Direct Cost : ¥5,400,000)
|Keywords||Chemokine / interleukin-8 / MCAF / MCP-1 / neutrophils / monocytes / inflammation / HIV infection / receptor / 糸球体腎炎 / 急性呼吸窮迫症候群|
This study was performed to develop novel types of anti-inflammatory and immunoregulatory agents through elucidating the pathophysiological roles of chemokines including interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1). Through these studies, we obtained the results as follows.
#1.In collaboration with Dr.Thestrup-Pedersen's group, we observed that IL-8 recetor expression on B cells was up-regulated in HIV-infected asymptomatic patients, compared with normal persons. Moreover, we observed that B cells from HIV-infeced patients responded differentially to various Th1 and Th2 cytokines, in terms of IL-8 receptor expression.
#2.In collaboration with Dr.Thestrup-Pedersen's group, we demonstrated that plasma IL-8 levels elevated immediately after the liver transplantation, probably reflecting reperfusion injury to transplanted organs.
#3.In collaboration with Dr.Oppenheim'sgroup, we demonstrated that IL-8 induced the phosphorylation of CXCR2 (IL-8 receptor type B) more strongly, than NAP-2. Moreover, we revealed the strong phosphorylation resulted in reduced neutrophil chemotactic activity in response to high concentrations of IL-8.
#4.In collaboration with Dr.Oppenheim, we established a sensitive enzyme-linked immunosorbent assay for a CC hemokine, eotaxin.
#5.We established the essential involvement of IL-8 in neutrophil-mediated tissue injuries, such as acute respiratory distress syndrome and brain reperfusion injury model of rabbit. Moreover, we revealed that MCAF/MCP-1 was crucially involved in anti-glomerular basement membrane antisera-induced crescentic shronic glomerulonephritis model.
#6.We demonstrated that cytomegalovirus induced IL-8 production in vitro and that IL-8 attenuated anti-viral activities of interferon.
The discussion with Drs.Thestrup-Pedersen and Oppenheim has given us invaluable advice when performing studies #5 and #6.