Epigenetic regulation of inflammation in localized aggressive periodontitis

Abstract

BackgroundWe have previously demonstrated a Toll-like receptor (TLR)-mediated hyper-responsive phenotype in our cohort of localized aggressive periodontitis (LAP) individuals. However, mechanisms related to this phenotype are still not clear in the literature. The objective of this cross-sectional study is to examine the role of epigenetic regulation, specifically DNA methylation status of genes in the TLR pathway in this cohort. Peripheral blood was collected from 20 LAP patients and 20 healthy unrelated controls. Whole blood was stimulated with 1 μl (100 ng/μl) of purified Escherichia coli lipopolysaccharide (LPS) for 24 h and cyto/chemokines in the supernatants analyzed by Luminex multiplex assays. Genomic DNA extracted from buffy coats prepared from a second tube of whole blood was used for DNA methylation analysis by pyrosequencing of seven TLR signaling genes (FADD, MAP3K7, MYD88, IL6R, PPARA, IRAK1BP1, RIPK2).ResultsSignificant differences in the methylation status were observed at specific CpG positions in LAP patients compared to healthy controls and interestingly also between severe and moderate LAP. Specifically, subjects with moderate LAP presented hypermethylation of both the upregulating (MAP3K7, MYD88, IL6R, and RIPK2) and downregulating (FADD, IRAK, and PPARA) genes, while severe LAP presented hypomethylation of these genes. Further analysis on CpG sites with significant differences in methylation status correlates with an increased pro-inflammatory cytokine profile for LAP patients.ConclusionsOur findings suggest that epigenetic modifications of genes in the TLR pathway may orchestrate the thresholds for balancing induction and prevention of tissue destruction during the course of disease, and thus differ significantly at different stages of the disease, where moderate LAP shows hypermethylation and severe LAP shows hypomethylation of several genes.Trial registration https://clinicaltrials.gov, NCT01330719

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DNA methylation profile of genes related to immune response in generalized periodontitis

“…Decreased methylation in the CCL25 and IL17C genes was demonstrated in gingival tissues of aggressive periodontitis . Considering different stages of localized aggressive periodontitis, the hypermethylation of MAP3K7 , MYD88 , IL6R, RIPK2, FADD, IRAK, and PPARA genes was observed in peripheral blood from individuals with moderate compared to severe periodontitis . These data suggest gene‐specific methylation pattern associated with disease.…”

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DNA methylation profiles of immune response‐related genes in apical periodontitis

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