Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada.
Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Physiol Lung Cell Mol Physiol. 2021 Feb 1;320(2):L165-L178. doi: 10.1152/ajplung.00303.2020. Epub 2020 Dec 9.
Inflammasomes are multiprotein complexes tasked with sensing endogenous or exogenous inflammatory signals and integrating this signal into a downstream response. Inflammasome activation has been implicated in a variety of pulmonary diseases, including pulmonary hypertension, bacterial pneumonia, COPD, and asthma. Of increasing interest is the contribution of inflammasome activation in the context of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Inflammasome activation in both the lung parenchyma and resident immune cells generates intereukin-1β (IL-1β) and IL-18, both of which drive the cascade of lung inflammation forward. Blockade of these responses has been shown to be beneficial in animal models and is a focus of translational research in the field. In this review, we will discuss the assembly and regulation of inflammasomes during lung inflammation, highlighting therapeutically viable effector steps. We will examine the importance of IL-1β and IL-18, two key products of inflammasome activation, in ALI, as well as the contribution of the pulmonary endothelial cell to this process. Finally, we will explore translational research moving toward anti-inflammasome therapies for ALI/ARDS and speculate toward future directions for the field.
炎症小体是多蛋白复合物，负责感知内源性或外源性炎症信号，并将此信号整合到下游反应中。炎症小体的激活与多种肺部疾病有关，包括肺动脉高压、细菌性肺炎、COPD 和哮喘。越来越引人关注的是炎症小体激活在急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）中的作用。肺实质和固有免疫细胞中的炎症小体激活会产生白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18），这两者都推动了肺部炎症的级联反应。在动物模型中，阻断这些反应已被证明是有益的，这也是该领域转化研究的重点。在这篇综述中，我们将讨论肺部炎症过程中炎症小体的组装和调节，重点介绍治疗上可行的效应步骤。我们将研究 IL-1β 和 IL-18 在 ALI 中的重要性，以及肺内皮细胞对这一过程的贡献。最后，我们将探讨针对 ALI/ARDS 的抗炎症小体治疗的转化研究，并对该领域的未来方向进行推测。
