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NLRP3 炎性小体在稳定期慢性阻塞性肺疾病中的激活。

Activation of NLRP3 inflammasome in stable chronic obstructive pulmonary disease.

机构信息

Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia.

Department of Medical Biochemistry and Haematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.

出版信息

Sci Rep. 2022 May 9;12(1):7544. doi: 10.1038/s41598-022-11164-1.

Abstract

Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays an important role in chronic obstructive pulmonary disease (COPD) pathogenesis and might be involved in ongoing chronic inflammation. This study aimed to determine interleukin-1beta (IL-1β) plasma concentration as well as IL1B, NLRP3 and caspase-1 (CASP1) gene expression in the Croatian COPD patients. 109 patients with stable COPD and age- and sex-matched 95 controls were included in the study. Plasma IL-1β concentration was measured by Luminex technology, and gene expression analysis was performed using TaqMan assays. It was shown that COPD patients had increased concentration of IL-1β and enhanced gene expression of IL1B, NLRP3 and CASP1 compared to controls. There was no difference in IL-1β or IL1B, NLRP3 and CASP1 in patients with COPD regarding airflow obstruction severity and smoking history. Finally, the diagnostic potential of the determined parameters was evaluated, and it was found that IL-1β correctly classified 89% of cases in the combination with common inflammatory biomarkers, white blood cell count and fibrinogen, showing a potential in COPD prediction. In conclusion, up-regulation of IL1B, NLRP3, CASP1 and increased IL-1β concentration suggest the activation of NLRP3 inflammasome in the systemic compartment of patients with stable COPD.

摘要

核苷酸结合寡聚化结构域样受体家族富含吡喃结构域蛋白 3(NLRP3)炎症小体的激活在慢性阻塞性肺疾病(COPD)发病机制中起着重要作用,并且可能与持续的慢性炎症有关。本研究旨在确定克罗地亚 COPD 患者的白细胞介素-1β(IL-1β)血浆浓度以及 IL1B、NLRP3 和半胱天冬酶-1(CASP1)基因表达。研究纳入了 109 例稳定期 COPD 患者和年龄及性别匹配的 95 例对照。采用 Luminex 技术测定血浆 IL-1β浓度,采用 TaqMan 法进行基因表达分析。结果显示,与对照组相比,COPD 患者的 IL-1β浓度升高,IL1B、NLRP3 和 CASP1 的基因表达增强。在 COPD 患者中,无论气流阻塞严重程度或吸烟史如何,IL-1β 或 IL1B、NLRP3 和 CASP1 均无差异。最后,评估了所确定参数的诊断潜力,发现 IL-1β 与常见炎症生物标志物白细胞计数和纤维蛋白原联合正确分类了 89%的病例,表明其在 COPD 预测中有一定的潜力。总之,IL1B、NLRP3、CASP1 的上调和 IL-1β 浓度的增加表明稳定期 COPD 患者全身炎症小体的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3db4/9085866/6cc47aaa36a1/41598_2022_11164_Fig1_HTML.jpg

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