Ji Meng-Lei, Dong Jin-Yuan, Xu Yan, Pan Yu-Ting, Fan Zhi-Dan, Yu Hai-Guo
Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China.
Department of Pediatrics, The First People's Hospital, Jiangsu University, Kunshan, Jiangsu, China.
Indian J Pediatr. 2023 Jan;90(1):22-28. doi: 10.1007/s12098-022-04126-y. Epub 2022 Mar 30.
To evaluate ITPKC and NLRP3 expression in children with Kawasaki disease (KD) and investigate the relationship between serum pro-inflammatory cytokines triggered by NLRP3 and inflammatory indices. Simultaneously, the methylation level in the ITPKC promoter was evaluated in children with KD.
Children who satisfied the American Heart Association diagnostic criteria for KD were enrolled in the study from August 2018 to January 2019. The levels of ITPKC, NLRP3, IL-1β, and IL-18 were measured. The effect of DNA methylation on the activity of the ITPKC promoter was observed. Methylation-specific PCR was used to verify methylation modification of the ITPKC promoter region in children with KD.
ITPKC expression was downregulated in patients with KD, whereas NLRP3 was upregulated. Expression of the downstream cytokine, IL-18, was significantly upregulated in children with KD and correlated positively with inflammatory indices. Modifying DNA methylation significantly decreased the luciferase activity of the plasmid containing the ITPKC promoter region and thus, may inhibit ITPKC gene promoter activity. Furthermore, methylation modification was observed in the ITPKC promoter region of children with KD.
Modification of DNA methylation inhibits ITPKC promoter activity and is involved in NLRP3 inflammasome activation in children with KD.
评估川崎病（KD）患儿中ITPKC和NLRP3的表达，并研究由NLRP3触发的血清促炎细胞因子与炎症指标之间的关系。同时，评估KD患儿ITPKC启动子中的甲基化水平。
2018年8月至2019年1月期间，将符合美国心脏协会KD诊断标准的儿童纳入研究。检测ITPKC、NLRP3、IL-1β和IL-18的水平。观察DNA甲基化对ITPKC启动子活性的影响。采用甲基化特异性PCR验证KD患儿ITPKC启动子区域的甲基化修饰。
KD患者中ITPKC表达下调，而NLRP3上调。KD患儿下游细胞因子IL-18的表达显著上调，且与炎症指标呈正相关。改变DNA甲基化显著降低了含有ITPKC启动子区域的质粒的荧光素酶活性，因此可能抑制ITPKC基因启动子活性。此外，在KD患儿的ITPKC启动子区域观察到甲基化修饰。
DNA甲基化修饰抑制ITPKC启动子活性，并参与KD患儿NLRP3炎性小体的激活。
