Prostaglandin E2, Immunity and hypertension

前列腺素（PGs）是花生四烯酸的氧化代谢产物，介导一系列生理功能 包括炎症和全身血压稳态。前列腺素E2（PGE 2）是一种主要的调节剂， 血压，在那里它发挥促高血压或抗高血压的影响，这取决于设置。 这些生理上相反的作用是由四种PGE 2受体介导的，称为E-前列腺素 (EP)受体EP 1至EP 4。我们小组和其他人以前的工作确定，EP 1和EP 3主要是 介导促高血压反应，而EP 2和EP 4受体介导抗高血压反应。 PG被很好地表征为炎症的效应物，因此PG在炎症的交叉点起作用 和血压稳态，使其成为原发性高血压病因学的潜在靶点。我们 假设EP受体调节免疫炎症细胞和强大的T细胞介导的免疫 反应导致高血压。此外，在免疫系统中多次重复刺激T细胞反应， 面对高血压刺激，例如作为盐负荷，PG调节以产生持续升高的血液 压力我们假设EP 3受体是促进PGE 2反应的主要受体， 血压.为了检验这些相关的假设，我们提出了三个具体的目标：1）检验假设， EP 3调节对重复促高血压刺激的反应，导致记忆T细胞的发育 潜在的持续血压升高; 2）测试ROS升高导致 新抗原刺激T细胞形成; 3）检验T细胞上EP受体表达 有助于高血压的产生。

Prostaglandins (PGs), oxidative metabolites of arachidonic acid, mediate an array of physiologic functions including inflammation and systemic blood pressure homeostasis. Prostaglandin E2 (PGE2) is a major regulator of blood pressure, where it exerts pro-hypertensive or anti-hypertensive effects depending upon the setting. These physiologically opposing effects are mediated by four PGE2 receptors, designated the E-Prostanoid (EP) receptors EP1 to EP4. Previous work by our group and others determined that EP1 and EP3 primarily mediate the pro-hypertensive response, while EP2 and EP4 receptors mediate the anti-hypertensive response. PGs are well characterized to be effectors of inflammation, and thus PGs act at the intersection of inflammation and blood pressure homeostasis, making them potential targets in the etiology of essential hypertension. Our hypothesis is that EP receptors regulate immune-inflammatory cells and a robust T-cell mediated immune response contributes to hypertension. Moreover, multiple, repeated stimulation of the T-cell response in the face of hypertensive stimuli such as salt loading is modulated by PGs to generate sustained elevated blood pressure. We hypothesize that the EP3 receptor is the principal receptor facilitating the PGE2 response to raise blood pressure. To test these related hypotheses we propose three Specific Aims: 1) Test the hypothesis that EP3 regulates the response to repeated pro-hypertensive stimuli leading to the development of memory T-cells underlying sustained elevation of blood pressure; 2) Test the hypothesis that elevated ROS leads to neoantigen stimulated T-cell formation; 3) Test the hypothesis that EP receptor expression on T-cells contributes to the generation of hypertension.