AIM2 炎性小体诱导的细胞焦亡对急性痛风性关节炎和无症状高尿酸血症患者的影响。
The impact of AIM2 inflammasome-induced pyroptosis on acute gouty arthritis and asymptomatic hyperuricemia patients.
机构信息
Department of Rheumatology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
Graduate School, Dalian Medical University, Dalian, Liaoning, China.
出版信息
Front Immunol. 2024 Jul 19;15:1386939. doi: 10.3389/fimmu.2024.1386939. eCollection 2024.
OBJECTIVE
This study aimed to evaluate the role of absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the pathogenesis of acute gouty arthritis (AGA) and asymptomatic hyperuricemia(AHU).
METHODS
A cohort of 30 AGA patients, 30 AHU individuals, and 30 healthy controls (HC) was assembled. Demographic and biochemical data, along with blood samples, were collected. Serum double-stranded DNA (dsDNA) levels were quantified using a fluorescent assay. Transcriptomic and proteomic analysis of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 in peripheral blood mononuclear cells was performed using qRT-PCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum IL-1β and IL-18. Spearman correlation analysis was utilized to assess relationships between variables.
RESULTS
Both AGA and AHU groups demonstrated elevated metabolic indicators and serum levels of dsDNA, IL-1β, and IL-18 compared to the HC group. AGA patients exhibited higher inflammatory markers than the AHU group. In the AGA group, there was a significant increase in the mRNA and protein levels of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 (P<0.05 to P<0.001). The AHU group showed higher AIM2, Caspase-1, GSDMD, and IL-18 mRNA levels than the HC group (P<0.001 to P<0.01), with a non-significant increase in AIM2, GSDMD, and IL-1β proteins (P>0.05). In contrast, Caspase-1 and IL-18 proteins were significantly higher in the AHU group (P<0.05). Notable correlations were observed between AIM2 protein expression and levels of Caspase-1 and GSDMD in both AGA and AHU groups. In the AGA group, AIM2 protein correlated with IL-1β, but not in the AHU group. The AIM2 protein in the AHU group was positively associated with IL-18, with no such correlation in the AGA group.
CONCLUSION
AIM2 inflammasome may play a role in the inflammatory processes of AGA and AHU and that its activation may be related to the pyroptosis pathway.
目的
本研究旨在评估缺失型黑色素瘤 2（AIM2）炎性小体介导的细胞焦亡在急性痛风性关节炎（AGA）和无症状高尿酸血症（AHU）发病机制中的作用。
方法
收集了 30 例 AGA 患者、30 例 AHU 个体和 30 例健康对照者（HC）的队列研究数据，包括人口统计学和生化数据以及血样。采用荧光法检测血清双链 DNA（dsDNA）水平。采用 qRT-PCR 和 Western blot 检测外周血单个核细胞中 AIM2、Caspase-1、GSDMD、IL-1β和 IL-18 的转录组和蛋白质组学。采用酶联免疫吸附试验（ELISA）测定血清 IL-1β和 IL-18。采用 Spearman 相关分析评估变量之间的关系。
结果
AGA 组和 AHU 组的代谢指标和血清 dsDNA、IL-1β和 IL-18 水平均高于 HC 组。AGA 患者的炎症标志物水平高于 AHU 组。AGA 组中 AIM2、Caspase-1、GSDMD、IL-1β和 IL-18 的 mRNA 和蛋白水平均显著升高（P<0.05 至 P<0.001）。AHU 组的 AIM2、Caspase-1、GSDMD 和 IL-18 mRNA 水平高于 HC 组（P<0.001 至 P<0.01），而 AIM2、GSDMD 和 IL-1β 蛋白水平无显著升高（P>0.05）。相反，Caspase-1 和 IL-18 蛋白在 AHU 组中显著升高（P<0.05）。在 AGA 和 AHU 两组中，AIM2 蛋白表达与 Caspase-1 和 GSDMD 水平之间存在显著相关性。在 AGA 组中，AIM2 蛋白与 IL-1β 相关，但在 AHU 组中不相关。在 AHU 组中，AIM2 蛋白与 IL-18 呈正相关，而在 AGA 组中则无相关性。
结论
AIM2 炎性小体可能在 AGA 和 AHU 的炎症过程中发挥作用，其激活可能与细胞焦亡途径有关。
Zotero 插件