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Role of the Inflammasome in Liver Disease
Annual Review of Pathology: Mechanisms of Disease ( IF 36.2 ) Pub Date : 2022-01-24 , DOI: 10.1146/annurev-pathmechdis-032521-102529
Marcelle de Carvalho Ribeiro 1 , Gyongyi Szabo 1
Affiliation  

The involvement of inflammasomes in the proinflammatory response observed in chronic liver diseases, such as alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), is widely recognized. Although there are different types of inflammasomes, most studies to date have given attention to NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) in the pathogenesis of ALD, NAFLD/nonalcoholic steatohepatitis, and fibrosis. Canonical inflammasomes are intracellular multiprotein complexes that are assembled after the sensing of danger signals and activate caspase-1, which matures interleukin (IL)-1β, IL-18, and IL-37 and also induces a form of cell death called pyroptosis. Noncanonical inflammasomes activate caspase-11 to induce pyroptosis. We discuss the different types of inflammasomes involved in liver diseases with a focus on (a) signals and mechanisms of inflammasome activation, (b) the role of different types of inflammasomes and their products in the pathogenesis of liver diseases, and (c) potential therapeutic strategies targeting components of the inflammasomes or cytokines produced upon inflammasome activation.

中文翻译:


炎症小体在肝病中的作用

炎症小体参与慢性肝病(例如酒精相关性肝病(ALD)和非酒精性脂肪肝病(NAFLD))中观察到的促炎症反应,这一点已得到广泛认可。尽管炎症小体有不同类型,但迄今为止大多数研究都关注NLRP3(核苷酸结合寡聚化结构域样受体家族,pyrin结构域包含3)在ALD、NAFLD/非酒精性脂肪性肝炎和纤维化发病机制中的作用。典型炎症小体是细胞内多蛋白复合物,在感知危险信号后组装并激活 caspase-1,使白细胞介素 (IL)-1β、IL-18 和 IL-37 成熟,并诱导一种称为细胞焦亡的细胞死亡形式。非典型炎症小体激活 caspase-11 诱导细胞焦亡。我们讨论了与肝脏疾病相关的不同类型的炎症小体,重点是(a)炎症小体激活的信号和机制,(b)不同类型的炎症小体及其产物在肝脏疾病发病机制中的作用,以及(c)潜在的作用。针对炎症小体成分或炎症小体激活时产生的细胞因子的治疗策略。

更新日期:2022-01-25
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