Role of a novel anti-inflammatory signaling mediated by EPRAP

EPRAP 介导的新型抗炎信号传导的作用

• 批准号: 20890111
• 负责人: MINAMI Manabu
• 金额: $ 2.11万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (Start-up)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20890111/
• 关键词: シグナル伝達; 炎症・免疫; マクロファージ

Macrophages participate in the pathogenesis of many chronic inflammatory diseases including atherosclerosis and cancer. Thus, the regulation of macrophage activation holds a key to understanding the pathophysiology and rational treatment of these conditions.We previously reported that PGE_2 markedly suppressed inflammatory activation of human and mouse primary macrophages through EP4 receptor and EPRAP, novel EP4 receptor-associated protein. To clarify the molecular mechanisms of EPRAP-mediated anti-inflammatory signaling in macrophages as well as to know the roles of EPRAP in human chronic diseases including atherosclerosis, we have been working on these projects : (1) production of the rabbit polyclonal antibody against human EPRAP, (2) purification of recombinant human EPRAP protein, and (3) generation of EPRAP mutant mice.Our study would add new insights into the mechanisms that may mitigate unchecked macrophage activation at sites of inflammation, and EP4-EPRAP signaling could be a novel target for the treatment of chronic inflammatory diseases.

巨噬细胞参与了许多慢性炎症性疾病的发病过程，包括动脉粥样硬化和癌症。因此，巨噬细胞激活的调控是理解这些疾病的病理生理机制和合理治疗的关键。我们先前报道PGE_2通过EP4受体和新的EP4受体相关蛋白EPRAP显著抑制人和小鼠原代巨噬细胞的炎性激活。为了阐明EPRAP介导的巨噬细胞抗炎信号的分子机制，以及了解EPRAP在包括动脉粥样硬化在内的人类慢性疾病中的作用，我们一直致力于以下项目：(1)制备抗人EPRAP的兔多克隆抗体，(2)纯化重组人EPRAP蛋白，(3)产生EPRAP突变小鼠。我们的研究将为减轻炎症部位巨噬细胞的无节制激活提供新的见解，EP4-EPRAP信号转导可能成为治疗慢性炎症性疾病的新靶点。

项目成果

C-C chemokine receptor 2 inhibitor improves diet-induced development of insulin resistance and hepatic steatosis in mice.

• DOI: 10.5551/jat.3368
• 发表时间: 2010-03
• 期刊: Journal of atherosclerosis and thrombosis
• 影响因子: 4.4
• 作者: Yukinori Tamura;M. Sugimoto;T. Murayama;M. Minami;Yuki Nishikaze;H. Ariyasu;T. Akamizu;T. Kita;M. Yokode;H. Arai

EP4受容体結合蛋白EPRAP/FEM1Aを中心とする新規抗炎症性分子ネットワークの心血管病発生における意義

以EP4受体结合蛋白EPRAP/FEM1A为中心的新型抗炎分子网络在心血管疾病发生发展中的意义

• 发表时间: 2009
• 期刊: Therapeutic Research 30(6)
• 作者: TAKAHASHI K;SOGA Y;MURAYAMA Y;et. al.;南学
• 通讯作者: 南学

Saji. 2008. Targeting of lectinlike oxidized low-density lipoprotein receptor 1 (LOX-1) with 99mTc-labeled anti-LOX-1 antibody: potential agent for imaging of vulnerable plaque

佐治。

• 期刊: J Nucl Med 49
• 作者: Kuge;Y.;N. Kume;S. Ishino;N. Takai;Y. Ogawa;T. Mukai;M. Minami;M. Shiomi;H. Saji
• 通讯作者: H. Saji

Prostaglandin E receptor type 4-associated protein (EPRAP) interacts directly with NF-κB1 p105 and attenuates macrophage activation

前列腺素 E 受体 4 型相关蛋白 (EPRAP) 直接与 NF-κB1 p105 相互作用并减弱巨噬细胞活化

• 发表时间: 2009
• 作者: Minami;M.;M. Yokode;P. Libby
• 通讯作者: P. Libby

Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis

• DOI: 10.1161/circresaha.107.164988
• 发表时间: 2008-02-01
• 期刊: CIRCULATION RESEARCH
• 影响因子: 20.1
• 作者: Okamoto, Yoshihisa;Folco, Eduardo J.;Libby, Peter
• 通讯作者: Libby, Peter