Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China; School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui Province, China.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):1184-1190. doi: 10.1016/j.bbrc.2020.10.003. Epub 2020 Oct 9.
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-1β levels but similar TNF-α, 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.
核苷酸结合域和富含亮氨酸重复家族pyrin 域包含 3（NLRP3）炎症小体参与各种急性和慢性肝病，但尚不清楚 NLRP3 是否有助于半乳糖胺（D-GalN）加脂多糖（LPS）诱导的急性肝衰竭（ALF）。本研究旨在研究 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，Nlrp3 和 WT 小鼠在接受致死剂量的 D-GalN/LPS 处理时表现出相似的死亡率。在 D-GalN/LPS 注射后 6 小时，Nlrp3 和 WT 小鼠的血清 ALT 和 AST 水平、肝坏死面积和肝细胞凋亡没有明显差异。此外，两种基因型小鼠在接受 D-GalN/LPS 处理后，肝内 F4/80 细胞和 Ly6G 细胞的数量相当。此外，与 WT 小鼠相比，Nlrp3 小鼠在给予 D-GalN/LPS 后 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 缺失不能保护小鼠免受 D-GalN/LPS 诱导的致命性肝炎，并且对 D-GalN/LPS 处理后肝内炎症反应的影响很小。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。
