Epigenetic regulation of TLR2-mediated periapical inflammation

A. Fernández, P. Veloso, J. Astorga, C. Rodríguez, V. A. Torres, M. Valdés, M. Garrido, P. J. Gebicke-Haerter, M. Hernández

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

Aim: To determine the methylation pattern of TLR2 gene promoter and its association with the transcriptional regulation of periapical inflammatory and angiogenic responses in symptomatic and asymptomatic forms of apical periodontitis. Methodology: In this cross-sectional study, apical lesions were obtained from volunteers with asymptomatic apical periodontitis (AAP) (n = 17) and symptomatic apical periodontitis (SAP) (n = 17) scheduled for tooth extraction, and both total RNA and DNA were extracted. DNA was bisulfite-treated, a region of CpG island within the TLR2 gene was amplified by qPCR and the products were sequenced. Additionally, the mRNA expression of TLR2, TLR4, IL-6, IL-12, TNFalpha, IL-23, IL-10, TGFbeta, VEGFA and CDH5 was analysed by qPCR. The data were analysed with chi-square tests, Mann–Whitney or unpaired t-tests, and Spearman´s correlation; variable adjustments were performed using multiple linear regression (P < 0.05). Results: TLR2 depicted a hypomethylated DNA profile at the CpG island in SAP when compared with AAP, along with upregulated expression of TLR2, with pro-inflammatory cytokines IL-6 and IL-23, and the angiogenesis marker CDH5 (P < 0.05). TLR2 methylation percentage negatively correlated with mRNA levels of IL-23 and CDH5 in apical periodontitis. Lower methylation frequencies of single CpG dinucleotides −8 and −10 localized in close proximity to nuclear factor κB (NFκB) binding within the TLR2 promoter were identified in SAP versus AAP (P < 0.05). Finally, unmethylated −10 and −8 single sites demonstrated up-regulation of IL-23, IL-10 and CDH5 transcripts compared to their methylated counterparts (P < 0.05). Conclusions: TLR2 gene promoter hypomethylation was linked to transcriptional activity of pro-inflammatory cytokines and angiogenic markers in exacerbated periapical inflammation. Moreover, unmethylated single sites in close proximity to NFκB binding were involved in active transcription of IL-23, IL-10 and CDH5.

Idioma originalInglés
Páginas (desde-hasta)1229-1237
Número de páginas9
PublicaciónInternational Endodontic Journal
Volumen53
N.º9
DOI
EstadoPublicada - 1 sep 2020

Áreas temáticas de ASJC Scopus

  • Odontología (todo)

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