Inouye Brian M, Hughes Francis M, Sexton Stephanie J, Purves J Todd
Department of Surgery, Division of Urology, Duke University Medical Center, Durham, NC, USA.
Curr Urol. 2018 Feb;11(2):57-72. doi: 10.1159/000447196. Epub 2017 Dec 30.
Irritative voiding symptoms (e.g. increased frequency and urgency) occur in many common pathologic conditions such as urinary tract infections and bladder outlet obstruction, and these conditions are well-established to have underlying inflammation that directly triggers these symptoms. However, it remains unclear as to how such diverse stimuli individually generate a common inflammatory process. Jürg Tschopp provided substantial insight into this conundrum when, working with extracts from THP-1 cells, he reported the existence of the inflammasome. He described it as a structure that senses multiple diverse signals from intracellular/extracellular sources and pathogens and triggers inflammation by the maturation and release of the pro-inflammatory cytokines interleukin-1β and interleukin-18. Recently, many of these sensors were found in the bladder and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, has been shown to be a central mediator of inflammation in several urological diseases. In this review, we introduce the nucleotide-binding domain, leucine-rich-containing family, pyrin domaincontaining-3 inflammasome, highlight its emerging role in several common urologic conditions, and speculate on the potential involvement of other inflammasomes in bladder pathology.
刺激性排尿症状(如尿频和尿急增加)在许多常见病理状况中都会出现,如尿路感染和膀胱出口梗阻,而且这些状况已被充分证实存在直接引发这些症状的潜在炎症。然而,目前尚不清楚如此多样的刺激如何各自引发一个共同的炎症过程。于尔格·楚普在研究THP - 1细胞提取物时,对这一难题给出了重要见解,他报告了炎性小体的存在。他将其描述为一种能感知来自细胞内/外来源及病原体的多种不同信号,并通过促炎细胞因子白细胞介素 - 1β和白细胞介素 - 18的成熟和释放来触发炎症的结构。最近,在膀胱中发现了许多这类传感器,并且含核苷酸结合结构域、富含亮氨酸家族、含pyrin结构域 - 3已被证明是几种泌尿系统疾病炎症的核心介质。在本综述中,我们介绍含核苷酸结合结构域、富含亮氨酸家族、含pyrin结构域 - 3炎性小体,强调其在几种常见泌尿系统疾病中日益凸显的作用,并推测其他炎性小体在膀胱病理中的潜在参与情况。