NLRP3 is dispensable for D-galactosamine/lipopolysaccharide-induced acute liver failure
NLRP3 is dispensable for D-galactosamine/lipopolysaccharide-induced acute liver failure
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NLRP3 对于 d-半乳糖胺/脂多糖诱导的急性肝衰竭是可有可无的
DOI：
10.1016/j.bbrc.2020.10.003
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Yang, Xiao-Ming
中科院分区：
文献类型：
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作者：
Zhang, Wen;Tao, Shou-Song;Yang, Xiao-Ming
核苷酸结合域和富含亮氨酸重复序列的家族pyrin结构域3（NLRP3）炎性体与多种急性和慢性肝病有关，然而，目前尚不清楚NLRP3是否有助于D-半乳糖胺（D-GalN）加脂多糖（LPS）诱导的急性肝衰竭（ALF）。本研究旨在探讨NLRP3炎症小体在D-GalN/LPS诱导的致命性肝炎中的作用。我们发现，对于致死剂量的 D-GalN/LPS 治疗，Nlrp3(-/-) 和 WT 小鼠表现出相似的死亡率。注射D-GalN/LPS后6小时，Nlrp3(-/-)和WT小鼠的血清ALT和AST水平以及肝坏死面积和肝细胞凋亡没有显着差异。此外，D-GalN/LPS治疗后，两只基因型小鼠的肝内F4/80(+)细胞和Ly6G(+)细胞数量相当。此外，与WT小鼠相比，给予D-GalN/LPS后，Nlrp3(-/-)小鼠的IL-1β水平降低，但TNF-α、IL-6和MCP-1水平相似。我们的研究结果表明，NLRP3 消除不能保护小鼠免受 D-GalN/LPS 诱导的致命性肝炎，并且对 D-GalN/LPS 治疗后的肝内炎症反应具有边际影响。这表明 NLRP3 炎症小体似乎不是 D-GalN/LPS 诱导的 ALF 的主要贡献者。 (C) 2020 由爱思唯尔公司出版
The nucleotide-binding domain and leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome is involved in various acute and chronic liver diseases, however, it is not clear whether NLRP3 contributes to D-Galactosamine (D-GalN) plus lipopolysaccharide (LPS)-induced acute liver failure (ALF). This study aims to investigate the role of NLRP3 inflammasome in D-GalN/LPS-induced fatal hepatitis. We found that Nlrp3(-/-) and WT mice showed similar mortality against a lethal dose of D-GalN/LPS treatment. Serum ALT and AST levels, as well as liver necrosis area and hepatocyte apoptosis, were not significantly different between Nlrp3(-/-) and WT mice at 6 h after D-GalN/LPS injection. Moreover, the numbers of intrahepatic F4/80(+) cells and Ly6G(+) cells were comparable in two genotype mice following D-GalN/LPS treatment. Besides, Nlrp3(-/-) mice had reduced IL-1 beta levels but similar TNF-alpha, IL-6, and MCP-1 levels compared with WT mice upon D-GalN/LPS administration. Our findings revealed that NLRP3 ablation does not protect mice from D-GalN/LPS-induced fatal hepatitis and has a marginal effect on intrahepatic inflammatory response upon D-GalN/LPS treatment. This suggests that NLRP3 inflammasome does not appear to be a major contributor to D-GalN/LPS-induced ALF. (C) 2020 Published by Elsevier Inc.