TNF-alpha gene promoter's hypomethylation mediates a pro-inflammatory phenotype in peripheral blood monocytes from apical periodontitis individuals

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dc.coverageDOI: 10.1111/iej.14162
dc.creatorFernández, Alejandra
dc.creatorBordagaray, María José
dc.creatorGarrido, Mauricio
dc.creatorPellegrini, Elizabeth
dc.creatorBaeza, Mauricio
dc.creatorChaparro, Alejandra
dc.creatorHernández, Patricia
dc.creatorHernández, Marcela
dc.date2025
dc.date.accessioned2025-11-18T19:43:53Z
dc.date.available2025-11-18T19:43:53Z
dc.description<p>Aim: Epigenetic regulation of the key inflammatory genes plays a crucial role in controlling monocyte/macrophage-mediated local and systemic responses to bacterial challenges. However, it has not been addressed in apical periodontitis (AP). We aimed to explore the methylation pattern of the TNF-α gene promoter and its association with the inflammatory phenotype of peripheral blood monocytes from individuals with AP and controls. Methods: A cross-sectional study was conducted, including otherwise healthy individuals with AP (n = 25) and controls (n = 29). Monocytes were isolated from the volunteer’s blood samples using a Ficoll gradient followed by negative immunoselection. RNA and DNA were extracted. The DNA methylation profiles of the TNF-α gene promoter region were analyzed using bisulfite sequencing PCR. The mRNA expression levels of DNA methyltransferases 3a (DNMT3a) and Ten Eleven Translocation enzymes 1(TET1) were assessed by qPCR. A fraction of primary monocytes was also cultured for 24 h, and the supernatant was collected to measure cytokine levels through a Luminex assay. Generalized structural equation models (GSEM) evaluated the association between AP, DNA methylation, and TNF-α protein expression controlled for potential covariates. Models included the effect of the methylation of TNF-α gene promoter as a mediator of the association between AP and TNF-α protein expression levels. Results: Monocytes from AP individuals exhibited a heightened secretion of TNF-α and IL-1β and hypomethylation of the TNF gene promoter (p &lt;.05). AP diagnosis was associated with the TNF-α gene promoter´s hypomethylated profile and enhanced pro-inflammatory cytokine levels, while lower methylation of the gene promoter region and -163 CpG single site mediated TNF-α overexpression (p &lt;.05). Conclusions: DNA hypomethylation at the TNF-α gene mediates a proinflammatory phenotype in monocytes from AP patients, supporting a role in the systemic response.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/a6f6834f-34fc-41c7-a78a-aec2e1d74130
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/53110
dc.languageeng
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.sourcevol.58 (2025) nr.2 p.284-294
dc.subjectDNA methylation
dc.subjectperiapical periodontitis
dc.subjecttumour necrosis factor-alpha
dc.titleTNF-alpha gene promoter's hypomethylation mediates a pro-inflammatory phenotype in peripheral blood monocytes from apical periodontitis individualseng
dc.typeArticleeng
dc.typeArtículospa
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