PDF(Pubmed)
Abstract：
Inflammatory bowel disease (IBD) is a debilitating condition that can lead to life-threatening complications. Macrophages are crucial in IBD management because they secrete various cytokines and regulate tissue repair. Macrophage-derived angiogenin (ANG) has been shown to be essential for limiting colonic inflammation, but its upstream regulatory pathway and role in macrophages remain unclear. Here we show that ANG expression is up-regulated in macrophages during colitis treatment or upon lipopolysaccharides (LPS) treatment. Mechanistically, LPS activates Toll-like receptor 4 (TLR4) to initiate NF-κB translocation from the cytoplasm to the nucleus, where it binds to the ANG promoter and enhances its transcriptional activity, leading to increased ANG expression. Interestingly, our data also reveal that the deletion of ANG in macrophages has no adverse effect on key macrophage functions, such as phagocytosis, chemotaxis, and cell survival. Our findings establish a \"LPS-TLR4-NF-κB-ANG\" regulatory axis in inflammatory disorders and confirm that ANG controls inflammation in a paracrine manner, highlighting the importance of ANG as a key mediator in the complex network of inflammatory processes.
摘要：
炎症性肠病（IBD）是一种使人衰弱的疾病，可导致危及生命的并发症。巨噬细胞在IBD管理中至关重要，因为它们分泌各种细胞因子并调节组织修复。巨噬细胞衍生的血管生成素（ANG）已被证明对限制结肠炎症至关重要，但其上游调控途径和在巨噬细胞中的作用尚不清楚。在这里，我们显示在结肠炎治疗期间或在脂多糖（LPS）治疗后，ANG表达在巨噬细胞中上调。机械上,LPS激活Toll样受体4（TLR4）启动NF-κB从细胞质到细胞核的易位，它与ANG启动子结合并增强其转录活性，导致ANG表达增加。有趣的是,我们的数据还显示，巨噬细胞中ANG的缺失对关键巨噬细胞功能没有不利影响，比如吞噬作用，趋化性,细胞存活。我们的发现在炎症性疾病中建立了“LPS-TLR4-NF-κB-ANG”调节轴，并证实ANG以旁分泌方式控制炎症，强调ANG作为炎症过程复杂网络中关键介质的重要性。
