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Inositol-Triphosphate 3-Kinase C and DNA Methylation Involvement in NLRP3 Inflammasome Activation in Kawasaki Disease

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Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

Modification of DNA methylation inhibits ITPKC promoter activity and is involved in NLRP3 inflammasome activation in children with KD.

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Data Availability

On reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81202345, 81771762).

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Author notes

  1. Zhi-Dan Fan and Hai-Guo Yu contributed equally to the paper.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Children’s Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China

    Meng-Lei Ji, Jin-Yuan Dong, Yan Xu, Yu-Ting Pan, Zhi-Dan Fan & Hai-Guo Yu

  2. Department of Pediatrics, The First People’s Hospital, Jiangsu University, Kunshan, Jiangsu, China

    Meng-Lei Ji

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  1. Meng-Lei Ji
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Contributions

J-ML, F-ZD, and Y-HG contributed to the conceptualization and study design; D-JY, XY, and P-YT interpreted and statistically analyzed the data; F-ZD and Y-HG were responsible for monitoring and data management, as well as reviewing and editing the manuscript; All authors were involved in drafting the article or revising it critically, and all authors approved the final version to be published. Y-HG will act as the guarantor for this paper.

Corresponding author

Correspondence to Zhi-Dan Fan.

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Ethics Approval

All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All study protocols were approved by the Ethics Committee of the Hospital.

Consent to Participate

All patients and healthy controls were informed about the study aim, and informed consent was obtained from their legal guardians.

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Ji, ML., Dong, JY., Xu, Y. et al. Inositol-Triphosphate 3-Kinase C and DNA Methylation Involvement in NLRP3 Inflammasome Activation in Kawasaki Disease. Indian J Pediatr 90, 22–28 (2023). https://doi.org/10.1007/s12098-022-04126-y

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  • DOI: https://doi.org/10.1007/s12098-022-04126-y

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