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Epigenetic regulation plays a pivotal role in controlling monocyte\/macrophage\u2010mediated local and systemic responses to bacterial challenges via\n                      <jats:italic>toll<\/jats:italic>\n                      \u2010like receptors (\n                      <jats:styled-content style=\"fixed-case\">TLRs<\/jats:styled-content>\n                      ). We aimed to explore the relationship between the methylation and expression patterns of\n                      <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\n                      \u20102 in peripheral blood monocytes of individuals with\n                      <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\n                      and controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Cross\u2010sectional study. Otherwise healthy individuals with AP (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200925) and controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929) were recruited. Peripheral blood monocytes were isolated from blood samples by Ficoll gradient and negative immunoselection. DNA and RNA were extracted from monocytes. DNA was bisulfite\u2010treated, amplified and sequenced to evaluate the global and cytosine\u2010phosphate\u2010guanine (CpG) single\u2010site methylation pattern of the TLR\u20102 gene promoter. mRNA relative levels of TLR\u20102 were assessed by qPCR. The potential associations between AP, TLR\u20102 DNA methylation and TLR\u20102 gene expression were explored using generalized structural equation models (GSEM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TLR\u20102 expression was significantly upregulated in peripheral blood monocytes from individuals with AP compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005). Though no differences were found in the global methylation pattern, CpG single sites from the TLR\u20102 gene were differentially methylated at positions \u221240 and +24 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). The methylated positions at \u221240 and \u221220 in TLR\u20102 were associated with TLR\u20102 transcriptional upregulation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Further evaluation with GSEM analysis showed that AP promoted the methylation of the \u221240 CpG single site on the TLR\u20102 gene, which, in turn, upregulated TLR\u20102. Conversely, the methylation of the \u221220 CpG single site did not act as a mediator of TLR\u20102 transcription in AP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AP diagnosis activates peripheral blood monocytes via \u221240 CpG single\u2010site methylation, independently promoting TLR\u20102 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.14255","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T08:26:10Z","timestamp":1747988770000},"page":"1172-1183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TLR<\/scp>\n                    \u20102 gene methylation in peripheral blood monocytes from apical periodontitis individuals: A cross\u2010sectional study"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-6045","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"Bordagaray","sequence":"first","affiliation":[{"name":"Laboratory of Periodontal Biology Faculty of Dentistry, Universidad de Chile  Santiago Chile"},{"name":"Department of Conservative Dentistry Faculty of Dentistry, Universidad de Chile  Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Universidad Andres Bello  Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Laboratory of Periodontal Biology Faculty of Dentistry, Universidad de Chile  Santiago 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Periodontal Biology Faculty of Dentistry, Universidad de Chile  Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Rehbein","sequence":"additional","affiliation":[{"name":"Laboratory of Periodontal Biology Faculty of Dentistry, Universidad de Chile  Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio","family":"Baeza","sequence":"additional","affiliation":[{"name":"Laboratory of Periodontal Biology Faculty of Dentistry, Universidad de Chile  Santiago Chile"},{"name":"Department of Conservative Dentistry Faculty of Dentistry, Universidad de Chile  Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Gebicke\u2010Haerter","sequence":"additional","affiliation":[{"name":"Institute of Psychopharmacology Central Institute of Mental Health, Faculty of Medicine, University of Heidelberg  Mannheim 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