An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes

被引：10
|
作者：
Grinstein, Lev [1 ]
Endter, Kristin [1 ]
Hedrich, Christian M. [1 ,2 ,3 ]
Reinke, Soeren [1 ]
Luksch, Hella [1 ]
Schulze, Felix [1 ]
Robertson, Avril A. B. [4 ]
Cooper, Matthew A. [4 ]
Roesen-Wolff, Angela [1 ]
Winkler, Stefan [1 ]
机构：
[1] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Pediat, Fetscherstr 74, D-01307 Dresden, Germany
[2] Univ Liverpool, Inst Translat Med, Dept Womens & Childrens Hlth, Liverpool, Merseyside, England
[3] Alder Hey Childrens NHS Fdn Trust Hosp, Dept Paediat Rheumatol, Liverpool, Merseyside, England
[4] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia
来源：
CLINICAL IMMUNOLOGY | 2018年 / 191卷
关键词：
Procaspase-1; Inflammasome; Whole blood assay; NLRP3; AIM2; NLRC4; INNATE IMMUNITY; HOST-DEFENSE; CELL-DEATH; ACTIVATION; SALMONELLA; CASPASE-1; MONOCYTES; POTASSIUM; INFECTION; PATHWAYS;
D O I：
10.1016/j.clim.2017.11.011
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
The proinflammatory protease caspase-1 plays pivotal roles in central pathways of innate immunity, thereby contributing to pathogen clearance. Beside its physiological role, dysregulated activity of caspase-1 is known to contribute to an increasing number of diseases. In this study, we optimized and validated a low-volume human whole blood assay facilitating the measurement of caspase-1 activation and inflammasome-related gene expression upon stimulation of the NLRP3, NLRC4 or AIM2 inflammasome. Using the NLRP3 inflammasome specific inhibitor MCC950, we were able to measure the activity of canonical or alternative NLRP3 pathways, AIM2 and NLRC4 inflammasomes in whole blood. Based on our data we assume a superposition of NLRP3 and NLRC4 inflammasome activities in human whole blood following stimulation with S. typhimurium. The optimized whole blood assay may be suitable for diagnostic and research purposes for pediatric patients who can only donate small amounts of blood. (C) 2017 Elsevier Inc. All rights reserved.
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收藏
页码：100 / 109
页数：10
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