Anti-inflammation therapy by activation of prostaglandin EP4 receptor in cardiovascular and other inflammatory diseases.
Anti-inflammation therapy by activation of prostaglandin EP4 receptor in cardiovascular and other inflammatory diseases.
复制标题
DOI：
10.1097/fjc.0b013e3182244a12
复制
发表时间：
2012-02
影响因子：
3
通讯作者：
Xu A
中科院分区：
文献类型：
--
作者：
Tang EH;Libby P;Vanhoutte PM;Xu A
前列腺素E2是炎症部位产生的环氧化酶-2衍生的主要前列腺素。体外和体内数据支持其作为炎症调节剂的作用。前列腺素E2通过与其受体之一前列腺素E受体4 （EP4）结合发挥抗炎作用，从而调节巨噬细胞和T淋巴细胞的功能，这些功能在先天免疫和适应性免疫以及组织重塑和修复中发挥重要作用。激活EP4可抑制巨噬细胞和T细胞中细胞因子和趋化因子的释放，抑制T细胞的增殖和活化，诱导T细胞凋亡。骨髓源性细胞中缺乏EP4会加速动脉粥样硬化和动脉瘤病变的局部炎症，并增加动脉瘤形成的发生率。EP4激动剂促进同种异体心脏移植的移植物存活，并减轻心肌缺血后的组织损伤。EP4激动作用的抗炎作用可能有益于其他炎性疾病，包括结肠炎和胃溃疡。相比之下，EP4在脑脊髓炎、皮肤炎症和关节炎中作为促炎介质，通过促进辅助性T (Th) 1的分化和Th17的扩增。总的来说，EP4激活在许多实验性疾病中产生强大的抗炎反应，使EP4激动剂成为减轻炎症相关综合征的有吸引力的药物。
Prostaglandin E2 constitutes a major cyclooxygenase-2-derived prostanoid produced at inflammatory sites. In vitro and in vivo data supports its role as a modulator of inflammation. Prostaglandin E2 exerts anti-inflammatory effects by binding to one of its receptors, the prostaglandin E receptor 4 (EP4), thereby modulating macrophage and T lymphocyte functions that participate crucially in innate and adaptive immunity and tissue remodeling and repair. Activation of EP4 suppresses the release of cytokines and chemokines from macrophages and T cells, inhibits the proliferation and activation of T cells, and induces T cell apoptosis. Lack of EP4 in bone marrow–derived cells accelerates local inflammation in atherosclerotic and aneurysm lesions and increases the prevalence of aneurysm formation. An EP4 agonist promotes graft survival in allograft cardiac transplantation and dampens tissue damage after myocardial ischemia. Anti-inflammatory actions of EP4 agonism may benefit other inflammatory disorders, including colitis and gastric ulcers. By contrast, EP4 acts as a pro-inflammatory mediator in encephalomyelitis, skin inflammation, and arthritis by promoting T helper (Th) 1 differentiation and Th17 expansion. Overall, EP4 activation produces powerful anti-inflammatory responses in many experimental diseases, rendering EP4 agonists attractive agents to attenuate syndromes associated with inflammation.