巨噬细胞“重塑”：脂氧素抑制COPD中炎性体活化的作用及机制研究

项目名称： 巨噬细胞“重塑”：脂氧素抑制COPD中炎性体活化的作用及机制研究

项目编号： No.81460002

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 况晓东

作者单位： 南昌大学

项目金额： 50万元

中文摘要： 炎症刹车因子脂氧素（LXs）与慢性阻塞性肺疾病（COPD）炎症密切相关，但其具体作用机制尚不明确。文献表明：巨噬细胞中的NLRP3炎性体被激活后，释放IL-1β等大量促炎因子，促进COPD炎症的发生；而巨噬细胞被LXs激活后，却可发挥强大的抗炎作用。以上巨噬细胞的双向炎性调节作用可能源于其可塑性- - 促炎M1型与抗炎M2型可逆性极化作用。我们前期研究发现：LXs可抑制NLRP3炎性体活化后促炎因子IL-1β的释放，并能促进巨噬细胞由M1向M2型转化。提示巨噬细胞亚型转变可能靶向调节NLRP3炎性体活化。本课题拟采用COPD炎症模型，考察炎性体活化与巨噬细胞极化间的动态变化规律，明确LXs对巨噬细胞的M1/M2型双向动态变化的重塑，进而影响NLRP3炎性体的活化，并进一步探究LXs对COPD炎症发挥调控作用的信号机制，以期为COPD药物开发提供新的思路和靶点。

中文关键词： 巨噬细胞；炎性体；慢性阻塞性肺病；极化

英文摘要： There is close relationship between chronic obstructive pulmonary diseases(COPD) and lipoxins(LXs),named as inflammatory brake factor,but the exact mechanism is not clear. Prvious reports have indicated that the NLRP3 inflammasome of macrophage could be activated and thereby induces the release of pro-inflammatory cytokines such as IL-1β,leading to initiation of chronic obstructive pulmonary diseases (COPD). However, LXs could also activate the macrophage, which negatively regulates gene expression involved in inflammation, yielding anti-inflammation response. Such a bipolar effect reflects the nature of macrophage plasticity: reversible conversion between pro-inflammatory M1 subtype and anti-inflammatory M2 subtype, a phenomenon also called polarization. Our previous studies indicated that LXs reduced the release of IL-1β by inhibiting NLRP3 inflammasome activation and pushed the macrophages skewing to the M2 type. This points to a possiblity that macrophage polarization inhibits the activation of NLRP3 inflammasome by targeted regulation. To test this hypothesis, we will employ the airway inflammation model of COPD to investigate dynamic change between the activation of NLRP3 inflammasome and macrophage polarization, assess the reshaping role of LXs in the dynamic change of macrophage M1/M2 transition, which will have great impact on activation of NLRP3 inflammasome. We will then further elucidate the mechanism underlying NLRP3 inflammasome activation. This proposed study will provide new ideas and targets COPD therapy.

英文关键词： macrophage polarization;inflammasome;COPD;polarization