1996 Fiscal Year Final Research Report Summary
Mechanism through which Kupffer cell-derived active oxidants mediate hepatoma cell injury
| Project/Area Number |
07670613
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
KUROSE Iwao School of Med.Internal Medicine, Keio University Instructor, 医学部・内科, 助手 (50234604)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Souichiro School of Med.Internal Medicine, Keio University Assistant Professor, 医学部・内科, 講師 (50138012)
KATO Shinzo School of Med.Internal Medicine, Keio University Assistant Professor, 医学部・内科, 講師 (30177448)
SAITO Hidetsugu School of Med.Internal Medicine, Keio University Assistant Professor, 医学部・内科, 講師 (80186949)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Hepatoma cell / Kupffer cell / NO / TNF-alpha / NF-kappaB / Adhesion molecules / Apoptosis / Laser scanning confocal microscope |
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| Research Abstract |
In 1995, we established the system which can determine productions of nitric oxide (NO) and TNF-alpha and apoptotic hepatoma cells with fragmented DNA and nuclear alterations. In 1996, by using laser scanning confocal microscope, we succeeded to visualize and analyze expression of mRNAs of inducible NO synthase (iNOS) and TNF-alpha. Investigations using these techniques revealed that coculture of Kupffer cells and hepatoma cells stimulate productions of NO and TNF-alpha, and these mediators released from Kupffer cells synergistically induce apoptosis of hepatoma cells. Inhibitor studies using antisense and sense oligodeoxynucleotides against mRNAs of iNOS and TNF-alpha, antibodies against adhesion molecules suggested that interactions via CD18 and ICAM-1 leads to activation and mediator production of Kupffer cells cocultured with hepatoma cells. We further established the method by which activated NF-kappaB can be visualized (Fluorescence in situ DNA-protein binding assay). By this assay, binding between CD18 and ICAM-1 have been demonstrated to lead to activation of NF-kappaB.
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