NF-kB control of neuronal apoptosis in Alzheimer disease

在2012财年，我们完成了以下工作： 1.确定了5种COX-2抑制剂中有3种抑制了CD4+T细胞中c-Rel的激活。所有这些抑制REL的药物也阻止了我们先前确定为塞来昔布靶点的几个REL反应的肿瘤坏死因子和肿瘤坏死因子受体超家族成员的上调。 2.我们发现塞来昔布在体外抑制了向炎性TH17细胞的分化，这不是由于抑制了谱系决定转录因子ROR-T。 3.使用不同剂量的塞来昔布，最大限度地抑制Rel与激活内质网应激是一致的。早期的研究表明，内质网应激导致核因子B的上调。我们的观察发现，内质网应激与特定的核因子B家族成员的下调之间存在新的联系。描述这些发现的手稿目前正在修改中。

During FY12 we accomplished the following: 1. Determined that 3 out of 5 COX-2 inhibitors suppressed c-Rel activation in CD4+ T cells. All those that inhibited Rel also prevented up-regulation of several Rel-responsive TNF and TNF-R super family members that we previously identified as targets of celecoxib. 2. We found that celecoxib inhibited differentiation to inflammatory TH17 cells in vitro This was not due to suppression of the lineage-determining transcription factor RORϒ-T. 3. Using celecoxib at different doses we found that maximal suppression of Rel coincided with activation of ER stress. Earlier studies have indicated that ER stress leads to up-regulation of NF-κB. Our observations provide a novel connection between ER stress and down-regulation of a specific NF-κB family member. A manuscript describing these findings is currently under revision.