The study of the role of 2 kinds of TNF receptors regulating the TNF-induced apoptosis in eosinophils.
| Project/Area Number |
09670466
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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 | Gunma University, School of Medicine |
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Principal Investigator |
DOBASHI Kunio FIRST DEPARTMENT OF INTERNAL MEDICINE, GUNMA UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (00241894)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | apoptosis / TNF / IFN-gannma / Eosinophil / TNFRI / TNFRII / EoL-1 / Rho / ROCK / TNF / γ-IFN |
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| Research Abstract |
Apoptosis is important for the resolution of chronic eosinophilic inflammation observed in bronchial asthma. Using a human myeloblastic leukemia cell line, EoL-1, we investigated the effect of interferon-gamma (IFN-γ) on Fas- and tumor becrosis factor-α (TNF)-induced apoptosis. Both THN and anti-Fas monoclonal antibody (CH-11) induced apoptosis of EoL-1 cells. Pretreatment with IFN-γ enhanced the CH-11-induced apoptosis with up-regulation of Fas. However, the treatment markedly inhibited the TNF-induced apoptosis. In flow cytometric analysis, EoL-1 expressed two types of tumor necrosis factor receptors (TNFR1, 2) and the expression of TNFR2 but not of TNFR1 was up-regulated significantly after the IFN-Γ treatment. The TNF-induced apoptosis was mimicked by a TNFR1 stimulating antibody (htr-9), and was reversed by a TNFR1 blocking antibody (H398). Although the TNFR1-mediated cytotoxic signal was not affected by IFN-γ pretreatment, blocking TNFR2 by a specific antagonistic antibody (utr-1
… More
) canceled the inhibitory effect of IFN-Γ. In conclusion, TNF-induced apoptosis was mediated preferentially by TNFR1, and the anti-apoptotic effect of IFN-γ result from up-regulated TNFR2 in EoL-1 cell line. Further, we investigated the signal transduction pathway from TNFR2 in IFN-γ treated EoL-1 cells. We revealed that the stimulation through TNFR2 activated the NF-kappaB by western blot analysis.
Recently, we reported that the effect of Rho/ROCK signaling on cell functions. Rho/Rock signaling inhibited the myosin phosphatase and kept the phosphoryrated myosin high. ROCK inhibitor (Y-27632) relaxed the muskarinic bronchiai smooth muscle contraction. Myosin is known to regulates the morphological change and migration of cells. So, we investigated the effect of ROCK inhibitor (Y-27632) on migration of eosinophols and found that Y-27632 inhibitted the migration of eosinophils without inhibitting the CaィイD1++ィエD1 influx or production of active oxygen. These findings were preparing for paper. Less
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Report
(4 results)
Research Products
(10 results)
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[Publications] Horie, T., Dobashi, K., Iizuka, K., Yoshii, K., Shimizu, Y., Nakazawa, T., and Mori, M.: "Interferon-gamma rescues TNF-alfa induced apoptosis mediated by up-regukation of TNFR2 on EoL-1 cells."Exp. Hematol.. 27. 512-519 (1999)
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[Publications] Dobashi, K. Horie, T., Iizuka, K., Aihara, M., Yoshii, A., Araki, T., Shimizu, Y., Koga, T., Nakazawa, T., and Mori, M.: "Interferon gamma rescues tumor necrosis factor induced apoptosis mediated by up regulation of tumor necrosis factor induced apoptosis meidated by up regulation of tumor necrosis factor receptor 2 on human eosinophilic leukemia cell line EoL-1"Am. J. Respir. Crit. Care. Med.. 159. 39-39 (1999)
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Related Report
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