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Updated: Dec 23, 2025
Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
Published on: November 28, 2015
Epigenetic Regulation of Macrophage Marker Expression Profiles in Kawasaki Disease
Mindy Ming-Huey Guo1,2,3, Ling-Sai Chang1,2, Ying-Hsien Huang1,2
1Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Insights
Kawasaki disease (KD) involves increased M1 and M2 macrophage markers in children. Intravenous immunoglobulin (IVIG) therapy reduced these markers, suggesting methylation influences macrophage behavior in KD.
Area of Science:
- Pediatric rheumatology
- Immunology
- Vascular inflammation
Background:
- Kawasaki disease (KD) is a leading cause of acquired heart disease in children.
- Activated macrophages are central to the vascular inflammation observed in KD.
- Understanding macrophage polarization in KD is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate M1 and M2 macrophage marker expression differences in pediatric KD patients.
- To explore the impact of intravenous immunoglobulin (IVIG) therapy on macrophage marker expression.
- To examine the role of CpG site methylation in macrophage polarization during KD.
Main Methods:
- Blood samples from 18 KD patients and 18 healthy controls were analyzed.
- GeneChip Human Transcriptome Array and Illumina HumanMethylation450 BeadChip were employed.
- mRNA expression and CpG methylation of 10 M1 and 15 M2 surface markers were assessed pre- and post-IVIG therapy.
Main Results:
- Increased mRNA expression of 2 M1 markers (TLR2, IL2RA) and 8 M2 markers (ARG1, CCR2, TLR1, TLR8, TLR5, MS4A6A, CD36, MS4A4A) was observed in acute KD.
- These marker expressions decreased significantly after IVIG treatment (P < 0.05).
- Corresponding CpG sites were hypomethylated in acute KD and hypermethylated after IVIG therapy.
Conclusions:
- Both M1 and M2 macrophage markers are upregulated during the acute phase of Kawasaki disease.
- CpG site methylation appears to be a significant regulatory mechanism for macrophage polarization in KD.
- These findings offer insights into KD pathogenesis and potential therapeutic targets.
Abstract:
Kawasaki disease (KD) is a common systemic vasculitides in children younger than 5 years of age. Activated macrophages are key drivers of vascular inflammation in KD. The aim of this study was to examine differences in M1 and M2 macrophage marker expression in patients with KD. Blood samples were obtained from 18 healthy controls and 18 patients with KD at 24 h prior and 21 days after to intravenous immunoglobulin therapy. GeneChip Human Transcriptome Array 2.0 and Illumina HumanMethylation450 BeadChip were used to examined the mRNA expression and corresponding CpG site methylation ratios of 10 M1 surface markers and 15 M2 surface markers. Of the markers examined 2 M1 markers (TLR2, IL2RA) and 8 M2 markers (ARG1, CCR2, TLR1, TLR8, TLR5, MS4A6A, CD36, and MS4A4A) showed increased mRNA expression in the acute phase of KD which decreased after IVIG therapy (P < 0.05). Corresponding CpG sites in the promoter regions these markers were hypomethylated in the acute phase of KD and significantly increased after IVIG therapy. In conclusion, both M1 and M2 markers showed increased mRNA expression in the acute phase of KD. CpG site methylation may be one of the mechanisms governing macrophage polarization in KD.
