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炎性体在炎症性肠病发病机制中的复杂作用——来自实验模型的经验教训。

The complex role of inflammasomes in the pathogenesis of Inflammatory Bowel Diseases - lessons learned from experimental models.

机构信息

Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain; Neuroscience Institute, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.

Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland.

出版信息

Cytokine Growth Factor Rev. 2014 Dec;25(6):715-30. doi: 10.1016/j.cytogfr.2014.04.003. Epub 2014 Apr 18.

Abstract

Inflammasomes are a large family of multiprotein complexes recognizing pathogen-associated molecular pattern molecules (PAMPs) and damage-associated molecular patterns (DAMPs). This leads to caspase-1 activation, promoting the secretion of mature IL-1β, IL-18 and under certain conditions even induce pyroptosis. Inflammatory Bowel Diseases (IBD) is associated with alterations in microbiota composition, inappropriate immune responses and genetic predisposition associated to bacterial sensing and autophagy. Besides their acknowledged role in mounting microbial induced host responses, a crucial role in maintenance of intestinal homeostasis was revealed in inflammasome deficient mice. Further, abnormal activation of these functions appears to contribute to the pathology of intestinal inflammation including IBD and colitis-associated cancer. Herein, the current literature implicating the inflammasomes, microbiota and IBD is comprehensively reviewed.

摘要

炎症小体是一大类多蛋白复合物,能够识别病原体相关分子模式(PAMPs)和损伤相关分子模式(DAMPs)。这导致半胱氨酸蛋白酶-1 的激活,促进成熟的白细胞介素-1β、白细胞介素-18 的分泌,在某些情况下甚至诱导细胞焦亡。炎症性肠病(IBD)与微生物群落组成的改变、免疫反应不当以及与细菌感知和自噬相关的遗传易感性有关。除了它们在引发微生物诱导的宿主反应中的公认作用外,炎症小体缺陷小鼠的研究揭示了它们在维持肠道内稳态方面的关键作用。此外,这些功能的异常激活似乎与肠道炎症包括炎症性肠病和结肠炎相关癌症的病理学有关。本文全面综述了炎症小体、微生物群和 IBD 的相关文献。

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