Role of a novel anti-inflammatory signaling mediated by EPRAP

巨噬细胞参与动脉粥样硬化和癌症等多种慢性炎症性疾病的发病机制。因此，巨噬细胞活化的调节是理解这些疾病的病理生理和合理治疗的关键。我们以前报道，PGE_2通过EP 4受体和EPRAP（一种新的EP 4受体相关蛋白）显著抑制人和小鼠原代巨噬细胞的炎症活化。为了阐明巨噬细胞中EPRAP介导的抗炎信号传导的分子机制，以及了解EPRAP在人类慢性疾病（包括动脉粥样硬化）中的作用，我们一直致力于这些项目：（1）兔抗人EPRAP多克隆抗体的制备，（2）重组人EPRAP蛋白的纯化，（3）EPRAP突变小鼠的产生，本研究为阐明炎症部位巨噬细胞活化的机制提供了新的思路，EP 4-EPRAP信号通路可能成为治疗慢性炎症性疾病的新靶点。

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.