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2017 ; 9
(ä): 94
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Epigenetic regulation of inflammation in localized aggressive periodontitis
#MMPMID28883894
Shaddox LM
; Mullersman AF
; Huang H
; Wallet SM
; Langaee T
; Aukhil I
Clin Epigenetics
2017[]; 9
(ä): 94
PMID28883894
show ga
BACKGROUND: We 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 ?l (100 ng/?l) 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). RESULTS: Significant
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. CONCLUSIONS: Our 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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