Epigenetic hypomethylation and upregulation of NLRC4 and NLRP12 in Kawasaki disease
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Ying-Hsien Huang1,2,3, Mao-Hung Lo1,2, Xin-Yuan Cai1,2 and Ho-Chang Kuo1,2
1Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
2Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
3Department of Pediatrics, Chiayi Chang Gung Memorial Hospital, Puzih-City, Taiwan
Keywords: NLRC4; NLRP12; Kawasaki disease
Received: November 30, 2017 Accepted: March 06, 2018 Published: April 10, 2018
INTRODUCTION: Kawasaki disease (KD) is a type of childhood febrile systemic vasculitis. Inflammasomes control inflammatory signaling and are related with the development of KD. In this study, we performed a survey of transcripts and global DNA methylation levels of inflammasome sensors of NOD-like receptors (NLRs) and the downstream interleukin 1β (IL-1β).
MATERIALS AND METHODS: In this study, for the chip studies, we recruited a total of 18 KD patients, who we analyzed before receiving intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, as well as 36 non-fever controls by Illumina HumanMethylation 450 BeadChip and Affymetrix GeneChip® Human Transcriptome Array 2.0. A separate group of 78 subjects was performed for real-time quantitative PCR validations.
RESULTS: The expressions of mRNA levels of NLRC4, NLRP12, and IL-1β were significantly upregulated in KD patients compared to the controls (p<0.05). Once KD patients underwent IVIG treatment, these genes considerably decreased. In particular, the methylation status of the CpG sites of these genes indicated a significant opposite tendency between the KD patients and the controls. Furthermore, mRNA levels of IL-1β represented a positive correlation with NLRC4 (p=0.002). We also observed that the mRNA levels of NLRP12 were lower in KD patients who developed coronary arterial lesions (p<0.005).
CONCLUSION: This study is among the first to report epigenetic hypomethylation, increased transcripts, and the upregulation of NLRC4, NLRP12 and IL-1β in KD patients. Moreover, a decreased upregulation of NLRP12 was related to coronary arterial lesion formation in KD patients.
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