{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:19:53Z","timestamp":1787167193532,"version":"build-2736575974"},"reference-count":82,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review aims to present the current understanding of endotoxin tolerance (ET) in chronic inflammatory diseases and explores the potential connection with periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Subsequent exposure to lipopolysaccharides (LPS) triggers ET, a phenomenon regulated by different mechanisms and pathways, including toll\u2010like receptors (TLRs), nuclear factor kappa\u2010light\u2010chain enhancer of activated B\u2010cells (NF\u03baB), apoptosis of immune cells, epigenetics, and microRNAs (miRNAs). These mechanisms interconnect ET with chronic inflammatory diseases including periodontitis. While the direct correlation between ET and periodontal destruction has not been fully elucidated, emerging reports point towards the potential tolerization of human periodontal ligament cells (hPDLCs) and gingival tissues with a significant reduction of TLR levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There is a potential link between ET and periodontal diseases. Future studies should explore the crucial role of ET in the pathogenesis of periodontal diseases, as evidence of a tolerized oral mucosa may represent an intrinsic mechanism capable of regulating the oral immune response. A clear understanding of this host immune regulatory mechanism might lead to effective and more predictable therapeutic strategies to treat chronic inflammatory diseases and periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jcpe.13591","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T22:22:43Z","timestamp":1640902963000},"page":"270-279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Understanding the role of endotoxin tolerance in chronic inflammatory conditions and periodontal disease"],"prefix":"10.1111","volume":"49","author":[{"given":"Lena","family":"Larsson","sequence":"first","affiliation":[{"name":"Department of Periodontology Institute of Odontology, The Sahlgrenska Academy University of Gothenburg  G\u00f6teborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Garaicoa\u2010Pazmino","sequence":"additional","affiliation":[{"name":"Department of Periodontics University of Iowa, College of Dentistry and Dental Clinics  Iowa City Iowa USA"},{"name":"School of Dentistry Esp\u00edritu Santo University  Samborondon Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-2645","authenticated-orcid":false,"given":"Farah","family":"Asa'ad","sequence":"additional","affiliation":[{"name":"Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy University of Gothenburg  G\u00f6teborg Sweden"},{"name":"Department of Oral Biochemistry, Institute of Odontology, The Sahlgrenska Academy University of Gothenburg  G\u00f6teborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5358-612X","authenticated-orcid":false,"given":"Rogerio Moraes","family":"Castilho","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"},{"name":"Laboratory of Epithelial Biology University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214681"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114147"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/eos.12657"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.2002.7.1.29"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.04.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.86.1.29"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.86.1.39"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/br.24.1.16-34.1960"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.90.4.970-977.1965"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.07.009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12549"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00423-008-0317-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01630"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.4248\/IJOS.09062"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-phyto-080614-120132"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.06.001"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803350"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500615"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31819c3c67"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02229-1"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067955"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05836"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13436"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0129-x"},{"issue":"6","key":"e_1_2_11_26_1","first-page":"1223","article-title":"Mechanisms of endotoxin tolerance. 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