{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:32:07Z","timestamp":1792521127533,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071126"],"award-info":[{"award-number":["82071126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate whether trained immunity occurs in gingival fibroblasts (GFs) and its relationship to the persistence of inflammation in periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Periodontally healthy and inflammatory gingival fibroblasts (HGFs and IGFs) were cultured through continuous adherence subculture of tissue blocks. Trained immunity in HGFs was evaluated via a classic in\u00a0vitro model, with relevant markers assessed via enzyme\u2010linked immunosorbent assay, lactate content assay, glycolytic rate assay, and chromatin immunoprecipitation. A histone methyltransferase blocker and a PI3K inhibitor were added to investigate the mechanisms underlying trained immunity. The relationship between trained immunity and periodontitis was further examined via immunofluorescence staining and chromatin immunoprecipitation on IGFs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with untrained cells, GFs trained with\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2010lipopolysaccharide (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P.\u2009gingivalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2010LPS) exhibited a significant increase in IL\u20106 and TNF\u2010\u03b1 secretion, enhanced glycolytic metabolism, and enriched mono\u2010methylation of lysine 4 on histone H3 (H3K4me1) at the enhancer regions of TNF\u2010\u03b1 and IL\u20106. The addition of a histone methyltransferase blocker and a PI3K inhibitor greatly reduced trained immunity. Additionally, the response of IGFs to\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P.\u2009gingivalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2010LPS stimulation and their epigenetic modifications were similar to those observed in trained HGFs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study novelly discovered that both\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P.\u2009gingivalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2010LPS\u2010stimulated HGFs and IGFs in periodontitis acquired trained immunity. Following\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P.\u2009gingivalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2010LPS stimulation, HGFs underwent metabolic and epigenetic changes via the PI3K\/AKT pathway, with these epigenetic changes also observed in IGFs. This finding suggests that trained immunity in GFs may be a key mechanism underlying the recurrence and persistence of periodontitis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.13372","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T05:19:04Z","timestamp":1733980744000},"page":"1156-1167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>Porphyromonas gingivalis<\/i>\n                    \u2010Lipopolysaccharide Induced Gingival Fibroblasts Trained Immunity Sustains Inflammation in Periodontitis"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3752-7504","authenticated-orcid":false,"given":"Jiayi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration &amp; 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