Sayan Mutlay, Mossman Brooke T
Department of Medicine, University of Vermont College of Medicine, 111 Colchester Avenue, Burlington, 05401, VT, USA.
Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, 05405, VT, USA.
Part Fibre Toxicol. 2016 Sep 20;13(1):51. doi: 10.1186/s12989-016-0162-4.
The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres. Most notably, inflammasome activation appears to regulate the balance between tissue repair and inflammation after inhalation of pathogenic pollutants such as asbestos, crystalline silica (CS), and airborne particulate matter (PM). Different types of fibres and particles may have distinct mechanisms of inflammasome interaction and outcome. This review summarizes the structure and function of inflammasomes, the interplay between various chemokines and cytokines and cell types of the lung and pleura after inflammasome activation, and the events leading to the development of non-malignant (allergic airway disease and chronic obstructive pulmonary disease (COPD), asbestosis, silicosis) and malignant (mesothelioma, lung cancer) diseases by pathogenic particulates. In addition, it emphasizes the importance of communication between cells of the immune system, target cells of these diseases, and components of the extracellular matrix (ECM) in regulation of inflammasome-mediated events.
炎性小体是一种感知细胞应激或危险信号并引发炎症的大分子复合物，其概念大约在十年前首次提出。这些细胞内蛋白质平台的启动和激活会触发促炎性趋化因子和细胞因子的成熟，最显著的是白细胞介素-1β（IL-1β）和IL-18，以促进先天性免疫防御。尽管炎性小体的启动和激活的重要性及作用机制在痛风、II型糖尿病、阿尔茨海默病和多发性硬化症模型中已有经典研究，但最近在呼吸道细胞中也得到了阐明，在呼吸道细胞中它们可调节对多种吸入的致病颗粒和纤维的反应。最值得注意的是，炎性小体激活似乎在吸入石棉、结晶硅（CS）和空气传播颗粒物（PM）等致病污染物后调节组织修复与炎症之间的平衡。不同类型的纤维和颗粒可能具有不同的炎性小体相互作用机制和结果。本综述总结了炎性小体的结构和功能、炎性小体激活后肺和胸膜的各种趋化因子、细胞因子与细胞类型之间的相互作用，以及致病颗粒导致非恶性疾病（过敏性气道疾病和慢性阻塞性肺疾病（COPD）、石棉沉着病、矽肺）和恶性疾病（间皮瘤、肺癌）发展的相关事件。此外，它强调了免疫系统细胞、这些疾病的靶细胞以及细胞外基质（ECM）成分之间的通讯在调节炎性小体介导事件中的重要性。
