ZFP91参与调控经典和非经典炎症小体活化及侧金盏花E干预机制研究

基于前期外专千人计划（WQ20122200065）项目研究中发现：ZFP91促进炎症因子IL-1β分泌，同时能够诱导NLRP3、ASC、caspase-1、caspase-8蛋白和mRNA的表达；ZFP91基因敲除小鼠IL-1β分泌水平低于野生型，因此认为ZFP91参与调控经典NLRP3-ASC-caspase-1和非经典NLRP3-ASC-caspase-8炎症小体活化从而诱导了IL-1β的分泌，然而其确切机理尚不明确。研究拟从分子（过表达、显性失活突变和RNA干扰）、细胞（功能）和整体（ZFP91基因敲除模型）不同层面，通过免疫共沉淀、免疫荧光和流式细胞等技术，以炎症小体活化为切入点，探索ZFP91对经典NLRP3-ASC-caspase-1和非经典NLRP3-ASC-caspase-8炎症小体调节机制，同时探讨侧金盏花E干预作用，以期为ZFP91/炎症小体为靶点的炎症诊治提供新策略。

The significant findings based on the preliminary experimental results of Thousands of Foreign Experts Plan (WQ20122200065): ZFP91 is functioned as a factor promoting inflammatory cytokine IL-1β release, as well as induces the expression of NLRP3, ASC, caspase-1, caspase-8 protein and mRNA. The IL-1β secretion level of mice with ZFP91 gene knockout is lower compared to the wild type. These results make us hypothesize that ZFP91 is involved in the regulation of canonical and non-canonical inflammasome activation and induced IL-1β secretion. However, the exact mechanism remains unclear. In this proposal, we will perform experiments at both molecular (over-expression, dominant negative mutation and RNA interference) and cellular (function) levels, as well as animal models (ZFP91 gene knockout mice), to figure out the role of ZFP91 in the regulation of canonical NLRP3-ASC-caspase-1 and noncanonical NLRP3-ASC-caspase-8 inflammasome activation. Finally, targeting the ZFP91/inflammasome using Calenduloside E as a therapeutic approach will be studied.