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揭示 NLRP3 炎性小体:结构建模和转录组分析的新见解。

Revealing the NLRP3 Inflammasome: Insights from Structural Modeling and Transcriptome Analysis.

机构信息

Biological Chemistry Laboratory, Institute of Chemistry, Faculty of Science, Pontificia Universidad Católica de Valparaíso, Valparaiso 2373223, Chile.

Escuela de Medicina Veterinaria, Facultad de Agronomía y Sistemas Naturales, Pontificia Universidad Católica de Chile, Santiago 7810000, Chile.

出版信息

Int J Mol Sci. 2023 Sep 26;24(19):14556. doi: 10.3390/ijms241914556.

Abstract

The NLRP3, one of the most heavily studied inflammasome-related proteins in mammals, remains inadequately characterized in (), despite the significant commercial importance of this salmonid. The NLRP3 inflammasome is composed of the NLRP3 protein, which is associated with procaspase-1 via an adapter molecule known as ASC. This work aims to characterize the NLRP3 inflammasome through in silico structural modeling, functional transcript expression determination in the SHK-1 cell line in vitro, and a transcriptome analysis on . The molecular docking results suggested a similar arrangement of the ternary complex between NLRP3, ASC, and caspase-1 in both the and the mammalian NLRP3 inflammasomes. Moreover, the expression results confirmed the functionality of the SsNLRP3 inflammasome in the SHK-1 cells, as evidenced by the lipopolysaccharide-induced increase in the transcription of genes involved in inflammasome activation, including ASC and NLRP3. Additionally, the transcriptome results revealed that most of the inflammasome-related genes, including ASC, NLRP3, and caspase-1, were down-regulated in the following its adaptation to seawater (also known as parr-smolt transformation). This is correlated with a temporary detrimental effected on the immune system. Collectively, these findings offer novel insights into the evolutionarily conserved role of NLRP3.

摘要

尽管这种鲑鱼具有重要的商业价值,但哺乳动物中研究最多的炎症小体相关蛋白 NLRP3 在 () 中的特征仍不够充分。NLRP3 炎症小体由 NLRP3 蛋白组成,该蛋白通过一种称为 ASC 的衔接分子与前胱天蛋白酶-1 相关联。这项工作旨在通过计算机结构建模、体外 SHK-1 细胞系中的功能转录表达测定以及 () 的转录组分析来表征 NLRP3 炎症小体。分子对接结果表明,NLRP3、ASC 和 caspase-1 的三元复合物在 () 和哺乳动物 NLRP3 炎症小体中的排列方式相似。此外,表达结果证实了 SsNLRP3 炎症小体在 SHK-1 细胞中的功能,这可以通过脂多糖诱导的参与炎症小体激活的基因(包括 ASC 和 NLRP3)转录增加来证明。此外,转录组结果表明,大多数炎症小体相关基因,包括 ASC、NLRP3 和 caspase-1,在适应海水(也称为幼鱼变流)后在 () 中下调。这与免疫系统暂时受到损害有关。总的来说,这些发现为 NLRP3 的进化保守作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2f7/10572965/00cc8151adc6/ijms-24-14556-g001.jpg

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