炎症性肠病中NLRP3炎性小体的激活：克罗恩病与溃疡性结肠炎的差异
Activation of NLRP3 Inflammasome in Inflammatory Bowel Disease: Differences Between Crohn's Disease and Ulcerative Colitis.
作者信息
Lazaridis Lazaros-Dimitrios, Pistiki Aikaterini, Giamarellos-Bourboulis Evangelos J, Georgitsi Marianna, Damoraki Georgia, Polymeros Dimitrios, Dimitriadis George D, Triantafyllou Konstantinos
机构信息
Hepatogastroenterology Unit, 2nd Department of Internal Medicine - Propaedeutic, Research Institute and Diabetes Center, Medical School, Attikon University General Hospital, National and Kapodistrian University, 1, Rimini Street, 124 62, Athens, Greece.
4th Department of Internal Medicine, Medical School, Attikon University General Hospital, National and Kapodistrian University, 1, Rimini Street, 124 62, Athens, Greece.
出版信息
Dig Dis Sci. 2017 Sep;62(9):2348-2356. doi: 10.1007/s10620-017-4609-8. Epub 2017 May 18.
BACKGROUND
NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β.
AIMS
To investigate NLRP3 inflammasome activation in inflammatory bowel disease.
METHODS
Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1β production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1β, TNFα, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping.
RESULTS
NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (p = 0.042); no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (p = 0.008) with long-standing disease (>1.5 years). IL-1β levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNFα, pro-IL-1β and in the numbers IL-1β, TNFα, NLRP3, and CASP1 transcripts among groups. IL-1β production was similar between carriers of wild-type and of SNP alleles of the rs2241880.
CONCLUSIONS
NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.
背景
NLRP3炎性小体是一种多分子胞质溶胶复合物，激活后可促使前白细胞介素（IL）-1β裂解为IL-1β。
目的
研究炎性肠病中NLRP3炎性小体的激活情况。
方法
在存在或不存在尿酸钠（MSU）的情况下，用脂多糖（LPS）刺激克罗恩病（CD）、溃疡性结肠炎（UC）患者及对照者的外周血单个核细胞。孵育后，检测细胞上清液中IL-1β、IL-6和肿瘤坏死因子α（TNFα）的浓度，并检测细胞裂解液中前IL-1β的浓度。NLRP3激活定义为添加MSU后IL-1β产生量增加超过30%。在单独的实验中，裂解外周血单个核细胞以分离RNA，通过逆转录聚合酶链反应（RT-PCR）检测IL-1β、TNFα、NLRP3和半胱天冬酶1（CASP1）的转录本。从CD患者中分离DNA进行自噬相关蛋白16样蛋白1（ATG16L1）基因分型。
结果
60%的CD患者NLRP3炎性小体被激活，而对照者为28.6%（p = 0.042）；UC患者与对照者之间未检测到显著差异。在UC患者中，NLRP3激活与病程较长（>1.5年）相关（p = 0.008）。与对照者相比，CD患者的IL-1β水平显著更高（p = 0.032）。各组之间IL-6、TNFα、前IL-1β水平以及IL-1β、TNFα、NLRP3和CASP1转录本数量均未检测到差异。rs2241880野生型携带者和单核苷酸多态性（SNP）等位基因携带者之间的IL-1β产生量相似。
结论
NLRP3炎性小体在CD患者以及病程较长的UC患者中被激活。
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