MECHANISM OF ACTION OF ANGIOTENSIN RECEPTOR BLOCKERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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而发挥抗炎作用。我们决定使用分子模型来快速评估哪些潜在的目标可能证明详细的实验室验证的费用是合理的。我们首先研究了VDR核受体，该受体被促性腺激素释放激素(GnRH)和甲状旁腺激素(PTH)等普遍存在的调节因子激活。此外，我们还检测了影响吞噬细胞功能的过氧化物酶体增殖物激活受体γ(PPARGamma)和C-C-趋化因子受体2b型(CCR2b)，后者将单核细胞招募到炎症免疫挑战的部位。

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.