1999 Fiscal Year Final Research Report Summary
Functional analysis of membrane TNF-α on activated T cells
| Project/Area Number |
10670417
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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 |
内科学一般
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
HORIUCHI Takahiko Dept of Medicine and Biosystemic Science, Kyushu University, Research associate, 大学院・医学系研究科, 助手 (90219212)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIZAKA Hiroaki Dept of Medicine and Biosystemic Science, Kyushu University, Research fellow, 医学部, 医員
YOSHIZAWA Shigeru Dept of Medicine and Biosystemic Science, Kyushu University, Research associate, 医学部, 助手 (20191562)
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| Project Period (FY) |
1998 – 1999
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| Keywords | TNF-α / E-selectin / CD4+ T cells |
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| Research Abstract |
The membrane tumor necrosis factor-α (TNF-α) is known to serve as a precursor of the soluble form of TNF-α. Although it has been reported the biological functions of the membrane TNF-α as a ligand, the reverse (outside-to-inside) signal transmitted through membrane TNF-α is poorly understood. We here report a novel function mediated by outside-to-inside signal via membrane TNF-α. Activation by anti-TNF-α antibody (Ab) against membrane TNF-α on HTLV-I-infected T cell line, MT-2, or PHA-activated normal human CD4+ T cells resulted in the induction of an adhesion molecule, E-selectin (CD62E), on the cells with the peak of 12 to 24 h, which was completely disappeared at 45 h. When wild-type or mutant membrane TNF-α (R78T/S79T) resistant to proteolytical cleavage was introduced into Jurkat or HeLa cells, E-selectin was induced by the treatment with anti-TNF-α Ab with the similar kinetics. Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that the membrane TNF-α-mediated E-selectin expression was upregulated at the level of transcription. These results not only confirmed our previous findings of reverse signaling through membrane TNF-α, but also presented for the first time that E-selectin was inducible in cell types different from endothelial cells. It is strongly suggested that membrane TNF-α is a novel proinflammatory cell surface molecule that transmit bipolar signals in local inflammation.
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[Publications] Horiuchi T, Nishizaka H, Kojima T, Sawabe T, Niho Y, Schneider PM, Inaba S, Sakai K, Hayashi K, Hashimura C, Fukumori Y:: "A nonsense mutation at Arg-95 is predominant in complement 9 deficiency in Japanese."J. Immunol.. 160. 1509-1513 (1998)
Description
「研究成果報告書概要(欧文)」より
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