The study of the role of 2 kinds of TNF receptors regulating the TNF-induced apoptosis in eosinophils.
The study of the role of 2 kinds of TNF receptors regulating the TNF-induced apoptosis in eosinophils.
批准号:
09670466
负责人:
DOBASHI Kunio
金额:
$2.37万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1999
中文摘要
凋亡是慢性碘化炎症观察到的慢性碘化炎症的一种重要方法。使用人类白血病细胞系,Eol-1,我们研究了干扰素-伽马(IFN-γ)对Fas-和肿瘤转化因子-α (TNF)诱导凋亡的影响。THN和反单克隆抗体(CH-11)诱导Eol-1细胞的凋亡。预处理与IFN-γ增强CH-11诱导性凋亡与Fas的上调调节。However,治疗市场上有效地抑制了TNF诱导的凋亡。在流动细胞学分析中,Eol-1表达了两种肿瘤坏死因子受体(TNFR 1, 2)的表达,而TNFR 2的表达,但在IFN-Γ治疗后,TNFR 1没有明显地进行了调整。TNF诱导的凋亡被TNFR 1刺激抗体(htr-9)模拟,被TNFR 1阻塞抗体(H398)逆转。也就是说,TNFR 1介导的细胞毒性信号不受IFN-γ预处理、阻断TNFR 2的影响(utr-1) ... More 消除了IFN-Γ的抑制作用。在整合中,TNF诱导的凋亡最好是TNFR 1介导的,而且IFN-γ在EOL-1细胞线中的反凋亡效应的结果。进一步,我们研究了IFN-γ处理的EOL-1细胞中TNFR 2的信号转移路径。我们通过西方印迹分析揭示了TNFR 2激活了NF-kappaB的刺激,最近,我们报告了Rho/ROCK信号对细胞功能的影响。Rho/Rock Signaling抑制了myosin磷酸酶,并保持了磷酸化的myosin很高。岩石抑制剂(Y-27632)放松了麝香玫瑰花光滑的麝香接触。Myosin是众所周知的,可以调节细胞的形态变化和迁移。因此,我们研究了ROCK抑制剂的影响(Y-27632),并发现了Y-27632抑制了没有抑制Cai-D1 ++ Yi-D1的活性氧的迁移或产生的e-D1。这些发现是为纸张准备的。Less(低)
英文摘要
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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Yoshii, K. iizuka, K. Dobashi, T. Horie, T. Harada, M. Mori, T. Nakazawa: "Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization."Am. J. Respir. Cell Mol. Biol.. 20. 1190-1200 (1999)
Yoshii、K. iizuka、K. Dobashi、T. Horie、T. Harada、M. Mori、T. Nakazawa:“Y-27632 通过抑制 Ca2 敏化来松弛收缩的兔气管和人支气管平滑肌。”
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通讯作者:
Horie T.,Dobashi K.et al.: "Interferon-gamma rescues TNF-alfa induced apoptosis mediated by up-regulation of TNFR2 on EoL-1 cells"Exp. Hematol.. 27. 512-519 (1999)
Horie T.、Dobashi K.等人:“干扰素-γ 可挽救 EoL-1 细胞上 TNFR2 上调介导的 TNF-α 诱导的细胞凋亡”Exp。
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通讯作者:
Takeo Horie: "Interferon-gamma rescues TNF-alfa induced apoptosis mediated by up-regulation of TNFR2 on EoL-1 cells." Exp.Hematol.(in press). (1999)
Takeo Horie:“干扰素 γ 可挽救 EoL-1 细胞上 TNFR2 上调介导的 TNF-α 诱导的细胞凋亡。”
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发表时间:
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通讯作者:
Yoshii K.et al.: "Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca^<2+> sensitization"Am. J. Respir. Cell Mol. Biol.. 20. 1190-1200 (1999)
Yoshii K.等人:“Y-27632 通过抑制 Ca^2 致敏作用来松弛收缩的兔气管和人支气管平滑肌”Am。
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通讯作者:
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
土桥 K.堀江 T.、饭冢 K.、相原 M.、吉井 A.、荒木 T.、清水 Y.、古贺 T.、中泽 T. 和森 M.:
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