炎症"程序性消退"介质RvE1在银屑病治疗中作用机制研究

炎症反应在启动同时就已经规划了炎症消退，通常呈现出一个高度有序化过程- - 炎症"程序性消退"(Programmed Resolution)。新近发现的内源性促炎症消退介质中，消退素RvE1不仅具有我们前期银屑病研究中脂氧素A4抗中性粒细胞趋化、促其凋亡和促巨噬细胞吞噬三大作用；而且具有在纳克级即发挥迄今为止最强大抗炎作用、不反馈性引起炎性因子增高（因来源于ω-3不饱和脂肪酸）等独特优势。本课题拟通过给予外源性的RvE1或阻断其受体ChemR23或/和BTL1作用，探讨RvE1对Th17细胞、TNF-α-NF-κB和RIP3通路的影响。通过细胞和动物实验，研究RvE1对角质形成细胞、Th17细胞、中性粒细胞、巨噬细胞功能的调节。从炎症"消退障碍"这一新角度阐述银屑病的发病机制，从"堵疏"兼顾的"抗炎与促进炎症消退"相结合这一新策略入手进行干预，期望对银屑病发病机制产生新认识，为治疗开辟新思路。

Emerging evidence now suggests that an active, coordinated program of resolution initiates in the first few hours after an inflammatory response begins. It shows a highly ordering process named "programmed resolution" of inflammation. Among the new classes of specialized pro-resolving lipid mediators, RvE1 shows the same effects as Lipoxin A4 (LXA4) which can prevent excessive inflammation and promote removal of microbes and apoptotic cells. It can shorten the period of neutrophil infiltration by initiating apoptosis. Consequently, apoptotic neutrophils undergo phagocytosis by macrophages, leading to neutrophil clearance and release of anti-inflammatory cytokines. More over, it has special features of the highest efficiency on diminishing inflammation by nano level dose; at the same time, it does not increasse the inflammatory cytokines for it is come from ω-3 unsaturated fatty acid. Thus we make a hypothesis that RvE1 could inhibit the occurrence of inflammation and also promote the resolution of inflammation. Upregulation and inhibition the funciton of RvE1 were adopted to analyse anti-inflammation effectiveness of RvE1 on Th17 cells, TNF-α-NF-κB and RIP3 pathways. We aim to study the regulatory efficacy of RvE1 on keratinocytes,Th17 cells, neutrophils and macrophages though cell culture and animal experiments. The aim of this project is to go further study in clarifying the mechanism how RvE1 can promote the resolution of the inflammation in psoriasis which may lead to a novel therapeutic strategy for treating skin inflammatory diseases such as psoriasis.