School of Health Sciences, University of Tasmania, Launceston, Tasmania 7250, Australia.
Int J Mol Sci. 2017 Nov 9;18(11):2379. doi: 10.3390/ijms18112379.
Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and hematopoitic interferon-inducible nuclear protein (HIN) domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated, some of these receptors oligomerize to form the structural backbone of a signalling platform known as an inflammasome. Inflammasomes promote the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. The gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome-deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population-based human studies. In this review, we summarise the most recent findings with regard to the formation, sensing, and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.
模式识别受体,如含有核苷酸结合寡聚化结构域(NOD)的蛋白受体(NLRs)和吡喃和造血干扰素诱导核蛋白(HIN)域(PYHIN)受体,在细胞应激或病原体挑战后启动炎症反应。当被激活时,这些受体中的一些寡聚化形成信号平台的结构骨架,称为炎症小体。炎症小体促进半胱天冬酶-1 的激活和前炎性细胞因子白细胞介素(IL)-1β和 IL-18 的成熟。炎症小体复合物在肠道失调被认为是炎症性肠病(IBD)发展的一个因素,如溃疡性结肠炎(UC)和克罗恩病(CD)。各种缺乏炎症小体的小鼠在葡聚糖硫酸钠(DSS)诱导的肠道炎症模型中以及在基于人群的人类研究中鉴定出新型潜在候选基因,强调了炎症小体对肠道健康的重要性。在这篇综述中,我们总结了关于炎症小体复合物的形成、感应和调节的最新发现,并强调了它们在维持肠道健康方面的重要性。