Hallett John M, Leitch Andrew E, Riley Nicola A, Duffin Rodger, Haslett Christopher, Rossi Adriano G
MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Trends Pharmacol Sci. 2008 May;29(5):250-7. doi: 10.1016/j.tips.2008.03.002. Epub 2008 Apr 11.
Resolution of inflammation requires the effective downregulation of key inflammatory cells such as neutrophils and eosinophils, which normally undergo programmed cell death (apoptosis) to enable their detection and removal by phagocytes such as macrophages. Dysregulation of this process is thought to contribute to the pathogenesis and progression of chronic inflammatory disorders such as chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, allergic rhinitis and inflammatory bowel disease. Importantly, knowledge of the signalling pathways responsible for the induction and execution of granulocyte apoptosis and the phagocytic removal of apoptotic cells continues to increase and, with it, the potential for incisive pharmacological intervention. In this article, we highlight pharmacological strategies that could be used to drive the resolution of inflammation by augmenting apoptosis of inflammatory cells.
炎症的消退需要有效下调关键炎症细胞,如中性粒细胞和嗜酸性粒细胞,这些细胞通常会经历程序性细胞死亡(凋亡),以便巨噬细胞等吞噬细胞对其进行识别和清除。该过程的失调被认为会导致慢性炎症性疾病,如慢性阻塞性肺疾病、哮喘、类风湿性关节炎、过敏性鼻炎和炎症性肠病的发病机制和进展。重要的是,负责粒细胞凋亡诱导和执行以及凋亡细胞吞噬清除的信号通路的知识不断增加,随之而来的是进行精准药物干预的潜力。在本文中,我们重点介绍了可用于通过增强炎症细胞凋亡来促进炎症消退的药理学策略。