Regulation mechanism for inflammation mediated by endothelial cell protein C receptor

内皮细胞蛋白C受体介导的炎症调节机制

• 批准号: 17591001
• 负责人: FUKUDOME Kenji
• 金额: $ 2.24万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591001/
• 关键词: protein C; endothelial cell; receptor; PAR; inflammation; トロンビン; 受容体; モノクローナル抗体

The endothelial cell protein C receptor (EPCR) is a type 1 transmembrane protein, which is capable of specific binding of protein C. We established monoclonal antibodies against the molecule, and demonstrated that EPCR was required for protein C activation under the physiological conditions. We also found that the binding function was not restricted to the zymogen form. Activated protein C (APC) bound to EPCR in the same manner as protein C. We detected EPCR expression in cancer cells. Complex formation of APC with EPCR on cancer cells may contribute to progression of cancer via catalytic activity to matrix metaroproteases. We also found the expression of the molecule on keratinocytes and microparticles. They may contribute to regulation of inflammation.It has been demonstrated that APC was useful for therapy of endotoxin shock. Lipopolysaccharide (LPS) is the causative agent, and is known to induce various cell responses mainly mediated by the cell surface complex of Toll-like receptor 4 and MD-2. LPS needs to be processed by LPS-binding protein and CD14 to be recognized by the cell surface receptor complex. To analyze how APC/EPCR complex affects to the LPS-signaling pathway, we prepared recombinant proteins of these molecules. We will try to analyze molecular mechanisms of cross talking between blood coagulation and inflammation.

内皮细胞蛋白C受体（EPCR）是一种1型跨膜蛋白，能够特异性结合蛋白C。我们建立了针对该分子的单克隆抗体，并证明在生理条件下EPCR是蛋白C激活所必需的。我们还发现结合功能并不限于酶原形式。活化蛋白 C (APC) 以与蛋白 C 相同的方式与 EPCR 结合。我们检测了癌细胞中的 EPCR 表达。 APC 与 EPCR 在癌细胞上的复合形成可能通过对基质元蛋白酶的催化活性促进癌症的进展。我们还发现了该分子在角质形成细胞和微粒上的表达。它们可能有助于调节炎症。已证明APC 可用于治疗内毒素休克。脂多糖 (LPS) 是致病因子，已知可诱导各种细胞反应，主要由 Toll 样受体 4 和 MD-2 的细胞表面复合物介导。 LPS需要经过LPS结合蛋白和CD14的加工才能被细胞表面受体复合物识别。为了分析 APC/EPCR 复合物如何影响 LPS 信号通路，我们制备了这些分子的重组蛋白。我们将尝试分析凝血和炎症之间相互作用的分子机制。

项目成果

Thrombus and encapsulated hematoma in cerebral cavernous malformations

• DOI: 10.1007/s00401-005-0994-8
• 发表时间: 2005-05-01
• 期刊: ACTA NEUROPATHOLOGICA
• 影响因子: 12.7
• 作者: Abe, M;Fukudome, K;Kawano, T
• 通讯作者: Kawano, T

Preparation and characterization of monoclonal antibodies to thrombomodulin.

血栓调节蛋白单克隆抗体的制备和表征。

• 发表时间: 2005
• 期刊: Hybridoma 24(4)
• 作者: Handa;Y. et al.;Kohara J.;Ohta S;Tsuneyoshi N;Imayoshi M;Kohara J;Tsuneyoshi N;Tsuneyoshi N
• 通讯作者: Tsuneyoshi N

Penta-acylated lipopolisaccharide binds to murine MD-2 but does not induce the oligomelization of TLR4 required for signal transduction

五酰化脂多糖与小鼠 MD-2 结合，但不会诱导信号转导所需的 TLR4 寡聚化

• 期刊: Cellular Immunology in press
• 作者: Harada H;et al.;Tsuneyoshi N;Ishiwata A;Tsuneyoshi N
• 通讯作者: Tsuneyoshi N

Expression of CD180, a toll-like receptor homologue, is up-regulated in children with Kawasaki disease

• DOI: 10.1007/s00109-005-0010-8
• 发表时间: 2006-02-01
• 期刊: JOURNAL OF MOLECULAR MEDICINE-JMM
• 影响因子: 4.7
• 作者: Imayoshi, M;Yamamoto, S;Ishii, E
• 通讯作者: Ishii, E

プロテインCとその受容体の機能

蛋白C及其受体的功能

• 发表时间: 2005
• 期刊: 血管医学 6(3)
• 作者: Imashuku S;et al.;常吉直子
• 通讯作者: 常吉直子