Deswaerte Virginie, Ruwanpura Saleela M, Jenkins Brendan J
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia; Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia.
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia; Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia.
Mol Immunol. 2017 Jun;86:3-9. doi: 10.1016/j.molimm.2016.09.023. Epub 2016 Sep 30.
Over the last decade it has emerged that inflammasome complexes provide a pivotal platform for the host innate immune system to respond to exogenous infectious microbes (viruses, bacteria, fungi) and non-infectious environmental agents (cigarette smoke, pollution), as well as endogenous "danger" signals. Upon the canonical activation of inflammasomes, a key effector function is to catalyze, via caspase-1, the maturation of the potent pro-inflammatory cytokines interleukin (IL)-1β and IL-18, which, in addition to chronic inflammatory responses have also been intimately linked to the inflammatory form of lytic cell death, pyroptosis. However, recent evidence suggests that inflammasomes exhibit marked pleiotropism beyond their canonical functions, whereby their activation can also influence a large number of cellular responses including proliferation, apoptosis, autophagy and metabolism. It is therefore not surprising that the dysregulated expression and/or activation of inflammasomes is increasingly implicated in numerous disease states, such as chronic auto-inflammatory and autoimmune disorders, metabolic syndrome, neurodegenerative and cardiovascular diseases, as well as cancer. In this review we will highlight recent advancements in our understanding of the transcriptional regulation of genes encoding inflammasome-associated innate immune receptors, and the impact on a variety of cellular responses during disease pathogenesis.
在过去十年中，已发现炎性小体复合物为宿主先天免疫系统提供了一个关键平台，以应对外源性感染微生物（病毒、细菌、真菌）和非感染性环境因子（香烟烟雾、污染）以及内源性“危险”信号。炎性小体经典型激活后，一个关键的效应功能是通过半胱天冬酶-1催化强效促炎细胞因子白细胞介素（IL）-1β和IL-18的成熟，除了慢性炎症反应外，它们还与溶解性细胞死亡的炎症形式——细胞焦亡密切相关。然而，最近的证据表明，炎性小体在其典型功能之外表现出显著的多效性，其激活还可影响大量细胞反应，包括增殖、凋亡、自噬和代谢。因此，炎性小体表达失调和/或激活越来越多地与多种疾病状态相关，如慢性自身炎症性和自身免疫性疾病、代谢综合征、神经退行性疾病和心血管疾病以及癌症，也就不足为奇了。在本综述中，我们将重点介绍我们对编码炎性小体相关先天免疫受体的基因转录调控的最新认识，以及在疾病发病机制中对多种细胞反应的影响。
