Anti-IL-6 activity of Notch signal : development of new therapeutic approaches for multiple myeloma

Notch信号的抗IL-6活性:多发性骨髓瘤新治疗方法的开发

基本信息

  • 批准号:
    15591001
  • 负责人:
  • 金额:
    $ 2.24万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

IL-6 is widely recognized as a major cytokine that stimulates the proliferation of myeloma cells through paracrine and autocrine mechanisms. We previously reported that IL-6 inhibits the differentiation of human blood monocytes into dermal dendritic cells. It is possible that IL-6 produced by myeloma cells is at least in part involved in the immune deficiency in patients with multiple myeloma. Our objective when we began this study was to restore the immune deficiency associated with multiple myeloma through anti-IL-6 signals. During the study, we incidentally found that the immobilized Notch ligand Delta-1 plays a crucial role in the differentiation of human blood monocytes into Langerhans cells. Recently, it was reported that Notch ligand Delta-1 is expressed in a proportion of the skin. GM-CSF and TGF-β1 are also secreted in the skin. We report here that Notch ligand Delta-1, in concert with GM-CSF and TGF-β1, induces the differentiation of human CD14^+ blood monocytes into cells th … More at express Langerhans cell markers : CD1a, Langerin, cutaneous lymphocyte-associated antigen, CC chemokine receptor 6, and E-cadherin. By transmission electron microscopy, the cells exhibited long prominent dendrites homogenously distributed on the cell surface and contained multiple organelles. Rod-or racket-shaped Birbeck granules with central lamella were encountered at a high frequency in the cell profiles. The cells display the phagocytic activity. In response to CD40 ligand and TNF-α, the cells acquire a mature phenotype of dendritic cells that is characterized by upregulation of HLA-ABC,HLA-DR,CD80,CD86,CD40,and CD54, and appearance of CD83. These cells elicit activation of CD8^+ T cells and Th1 polarization of CD4^+ T cells. Thus, human blood monocytes can be instructed to differentiate into Langerhans cells upon exposure to Notch ligand Delta-1,GM-CSF,and TGF-β1,which may be in part relevant to the development of human epidermal Langerhans cells. Our results not only extend the functional scope of Notch ligand Delta-1 in human hematopoiesis but also provide with the possibility to apply Langerhans cells to cellular immunotherapy for hematological malignancies such as multiple myeloma. Less
IL-6被广泛认为是通过旁分泌和自分泌机制刺激骨髓瘤细胞增殖的主要细胞因子。我们以前报道过IL-6抑制人血单核细胞向真皮树突状细胞的分化。骨髓瘤细胞产生的IL-6可能至少部分参与了多发性骨髓瘤患者的免疫缺陷。当我们开始这项研究时,我们的目标是通过抗IL-6信号恢复与多发性骨髓瘤相关的免疫缺陷。在研究过程中,我们偶然发现固定化Notch配体Delta-1在人血单核细胞分化为朗格汉斯细胞中起着至关重要的作用。最近,据报道,Notch配体Delta-1在皮肤的一定比例中表达。GM-CSF和TGF-β 1也在皮肤中分泌。我们在此报道Notch配体Delta-1与GM-CSF和TGF-β 1共同诱导人CD14 ^+血单核细胞分化为CD14 ^+细胞。 ...更多信息 表达朗格汉斯细胞标志物:CD1a、Langerin、皮肤淋巴细胞相关抗原、CC趋化因子受体6和E-钙粘蛋白。透射电镜观察细胞表面有长而突出的树突,树突均匀分布于细胞表面,细胞内含有多个细胞器。杆状或球拍形的Birbeck颗粒与中央片层遇到了一个高频率的细胞配置文件。细胞显示吞噬活性。响应于CD40配体和TNF-α,细胞获得树突状细胞的成熟表型,其特征在于HLA-ABC、HLA-DR、CD80、CD86、CD40和CD54的上调以及CD83的出现。这些细胞引起CD8 ^+ T细胞的活化和CD4 ^+ T细胞的Th1极化。因此,在暴露于Notch配体Delta-1、GM-CSF和TGF-β 1后,人血液单核细胞可被指示分化成朗格汉斯细胞,这可能部分与人表皮朗格汉斯细胞的发育相关。我们的研究结果不仅扩展了Notch配体Delta-1在人类造血中的功能范围,而且为Langerhans细胞应用于恶性血液病(如多发性骨髓瘤)的细胞免疫治疗提供了可能性。少

项目成果

期刊论文数量(43)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Fluorescent in situ hybridization analysis of Philadelphia chromosome-negative chronic myeloid leukemia with the bcr/abl fusion gene.
bcr/abl 融合基因对费城染色体阴性慢性粒细胞白血病的荧光原位杂交分析。
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Monma F;Nishii K;Yamamori S;Hosokai N;Nakazaki T;Lorenzo FV;Usui E;Sakakura M;Miyashita H;Fujieda A;Ohishi K;Katayama N;Shiku H
  • 通讯作者:
    Shiku H
Nishii K, et al.: "Characterization of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality : concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML"Leukemia. 17・4. 731-737 (2003)
Nishii K 等人:“伴有额外染色体异常的 t(8;21) 急性髓性白血病 (AML) 的特征:伴随的 4 号三体性可能构成 t(8;21) AML 的独特亚型”白血病 17・4。 731-737 (2003)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Sugimoto Y, et al.: "Acute myeloid leukemia with t(8;21)(q22;q22) manifesting as granulocytic sarcoma in the rhinopharynx and external acoustic meatus at relapse after high-dose cytarabine : case report and review of the literature"Hematol J. 5・1. 84-89 (
Sugimoto Y 等人颗粒:“急性髓性白血病伴 t(8;21)(q22;q22),表现为鼻咽和外耳道中的卵细胞肉瘤,在高剂量阿糖胞苷后复发:病例报告和文献综述” Hematol J.5・1.84-89(
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML
  • DOI:
    10.1038/sj.leu.2402871
  • 发表时间:
    2003-04-01
  • 期刊:
  • 影响因子:
    11.4
  • 作者:
    Nishii, K;Usui, E;Shiku, H
  • 通讯作者:
    Shiku, H
Activities of granulocyte-macrophage colony-stimulating factor and interleukin-3 on monocytes
  • DOI:
    10.1002/ajh.20010
  • 发表时间:
    2004-04-01
  • 期刊:
  • 影响因子:
    12.8
  • 作者:
    Suzuki, H;Katayama, N;Shiku, H
  • 通讯作者:
    Shiku, H
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

KATAYAMA Naoyuki其他文献

KATAYAMA Naoyuki的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('KATAYAMA Naoyuki', 18)}}的其他基金

Analysis of a role for BCR-ABL1 in the leukemogenesis using the experimental system that reflects the characteristics of human leukemia
利用反映人类白血病特征的实验系统分析BCR-ABL1在白血病发生中的作用
  • 批准号:
    21591200
  • 财政年份:
    2009
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The role for skin environment in the commitment of human monocytesto Langerhans cells
皮肤环境在人单核细胞向朗格汉斯细胞定型中的作用
  • 批准号:
    19591106
  • 财政年份:
    2007
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Lineage switch of human B cells to macrophages: relevance to the pathophysiology of Hodgkin lymphoma
人类 B 细胞向巨噬细胞的谱系转换:与霍奇金淋巴瘤病理生理学的相关性
  • 批准号:
    17590993
  • 财政年份:
    2005
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

NSF/MCB-BSF: Modeling the mechanisms that define Notch signal strength using in-vivo synthetic and quantitative biology
NSF/MCB-BSF:使用体内合成和定量生物学对定义 Notch 信号强度的机制进行建模
  • 批准号:
    2114950
  • 财政年份:
    2021
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Continuing Grant
Nrf2/Notch signal pathways contributing to ON/OFF regulation in sustained livre regeneration
Nrf2/Notch 信号通路有助于持续肝再生中的开/关调节
  • 批准号:
    18K06042
  • 财政年份:
    2018
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Clarifying the significance of Notch signal activation in B-cell lymphomas
阐明 Notch 信号激活在 B 细胞淋巴瘤中的意义
  • 批准号:
    18K08324
  • 财政年份:
    2018
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Trial of jaw bone regeneration based on Notch signal regulation of iPS cells
基于iPS细胞Notch信号调节的颌骨再生试验
  • 批准号:
    17K17148
  • 财政年份:
    2017
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
The role of HDAC3 in Notch signal transduction
HDAC3在Notch信号转导中的作用
  • 批准号:
    393040308
  • 财政年份:
    2017
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Research Grants
The regulation of glioma stem cell by the transcription factor "RBPJ" suppression in Notch signal
Notch信号转录因子“RBPJ”抑制对胶质瘤干细胞的调控
  • 批准号:
    17K10858
  • 财政年份:
    2017
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Cathepsin K-Notch signal pathway and sarcopenia
组织蛋白酶 K-Notch 信号通路与肌肉减少症
  • 批准号:
    15H04801
  • 财政年份:
    2015
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of maintenance mechanism of intestinal homeostasis through control of small intestinal epithelial lymphocytes by Notch signal
通过Notch信号控制小肠上皮淋巴细胞阐明肠道稳态的维持机制
  • 批准号:
    15K19131
  • 财政年份:
    2015
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Analysis of Notch signal pathway in epidermal regeneration and its application to therapy
Notch信号通路在表皮再生中的分析及其在治疗中的应用
  • 批准号:
    26461686
  • 财政年份:
    2014
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of Notch signal pathway in adipogenesis
Notch信号通路在脂肪生成中的调控
  • 批准号:
    25461336
  • 财政年份:
    2013
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了