MECHANISM OF ACTION OF ANGIOTENSIN RECEPTOR BLOCKERS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 有迹象表明，常见的血管紧张素受体阻滞剂（ARB）可能通过直接调节免疫系统发挥抗炎作用。我们决定使用分子建模来快速评估哪些潜在目标可能证明详细的实验室验证费用是合理的。我们首先研究了VDR核受体，它被开环类固醇激素1，25二羟维生素D激活。该受体介导调节剂的表达，如GnRH（促性腺激素释放激素）和甲状旁腺激素（PTH）。此外，我们还检测了过氧化物酶体激活受体γ（PPARgamma），它影响吞噬细胞的功能，以及C-C趋化因子受体，2b型（CCR 2b），它将单核细胞募集到炎症免疫攻击的部位。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There have been indications that common Angiotensin Receptor Blockers (ARBs) may be exerting anti-inflammatory actions by directly modulating the immune system. We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation. We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25 dihydroxyvitamin D. This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone) and the Parathyroid Hormone (PTH). Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma), which affects the function of phagocytic cells, and the C C Chemokine Receptor, type 2b, (CCR2b), which recruits monocytes to the site of inflammatory immune challenge.