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TLR4/TRIF 介导的 NLRP3 炎性小体激活导致小鼠内毒素诱导的肝损伤。

The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice.

机构信息

Department of Microbiology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8501, Japan.

出版信息

Gastroenterol Res Pract. 2010;2010:641865. doi: 10.1155/2010/641865. Epub 2010 Jun 16.

DOI:10.1155/2010/641865
PMID:20634907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2904443/
Abstract

Administration of heat-killed Propionibacterium acnes renders mice highly susceptible to LPS. After LPS challenge P. acnes-primed mice promptly show hypothermia, hypercoagulation (disseminated intravascular coagulation), elevation of serum proinflammatory cytokine levels, and high mortality. The surviving mice develop liver injury. As previously reported, IL-18 plays a pivotal role in the development of this liver injury. Many cell types including macrophages constitutively store IL-18 as biologically inactive precursor (pro) form. Upon appropriate stimulation exemplified by TLR4 engagement, the cells secrete biologically active IL-18 by cleaving pro-IL-18 with caspase-1. Caspase-1 is also constitutively produced as a zymogen in macrophages. Recently, NLRP3, a cytoplasmic pathogen sensor, has been demonstrated to be involved in the activation of caspase-1. Here, we review the molecular mechanisms for the liver injuries, particularly focusing on the TLR4/NLRP3-mediated caspase-1 activation process, with a brief introduction of the mechanism underlying P. acnes-induced sensitization to LPS.

摘要

经热处理的痤疮丙酸杆菌给药使小鼠对 LPS 高度敏感。在 LPS 挑战后，痤疮丙酸杆菌预刺激的小鼠迅速出现体温过低、高凝（弥散性血管内凝血）、血清促炎细胞因子水平升高和高死亡率。存活的小鼠会出现肝损伤。如前所述，IL-18 在这种肝损伤的发展中起着关键作用。许多细胞类型包括巨噬细胞，它们将 IL-18 作为无生物活性的前体（pro）形式储存。在 TLR4 结合等适当刺激下，细胞通过用半胱天冬酶-1切割 pro-IL-18 来分泌具有生物活性的 IL-18。半胱天冬酶-1也作为巨噬细胞中的酶原持续产生。最近，已证明细胞质病原体传感器 NLRP3 参与了半胱天冬酶-1 的激活。在这里，我们综述了肝损伤的分子机制，特别是重点介绍了 TLR4/NLRP3 介导的半胱天冬酶-1 激活过程，并简要介绍了痤疮丙酸杆菌诱导对 LPS 敏感的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/e4a0ff671ea9/GRP2010-641865.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/88e1269c25d4/GRP2010-641865.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/0816060ec01f/GRP2010-641865.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/c8fabf38838f/GRP2010-641865.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/f35db630fede/GRP2010-641865.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/25fee6f85562/GRP2010-641865.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/885a2bab6c3f/GRP2010-641865.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/e4a0ff671ea9/GRP2010-641865.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/88e1269c25d4/GRP2010-641865.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/0816060ec01f/GRP2010-641865.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/c8fabf38838f/GRP2010-641865.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/f35db630fede/GRP2010-641865.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/25fee6f85562/GRP2010-641865.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/885a2bab6c3f/GRP2010-641865.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c97/2904443/e4a0ff671ea9/GRP2010-641865.007.jpg

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