{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:06:37Z","timestamp":1788930397231,"version":"build-2803163510"},"reference-count":167,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Periodontitis is a chronic, dysbiosis-driven inflammatory disease, that, unlike gingivitis, results in irreversible, tooth-supporting soft tissue and bone loss. Clarifying the molecular pathways that sustain the host inflammatory response is therefore central to improving disease management. Lipopolysaccharide (LPS), a major pathogen-associated molecular pattern of Gram-negative bacteria, is one important\u2014though not the sole\u2014microbial stimulus that drives inflammation in the polymicrobial, dysbiotic periodontal environment. This narrative review summarizes how LPS-initiated signaling promotes production of the pro-inflammatory cytokines TNF-\u03b1 and IL-1, how these cytokines couple inflammation to osteoclast-mediated bone loss, and whether their pharmacological blockade holds therapeutic promise. A literature search combining the terms \u201cLPS,\u201d \u201cperiodontitis,\u201d \u201cTNF-\u03b1,\u201d and \u201cIL-1\u201d was conducted in PubMed\/MEDLINE, Scopus, and Google Scholar for English-language articles published up to 2026, with priority given to primary studies over secondary citations. Preclinical models consistently show that TNF-\u03b1 and IL-1 blockade reduces periodontal inflammation and bone loss, but the effect is time-dependent: short-term blockade can aid healing whereas prolonged blockade may impair it, and robust periodontitis-specific clinical trials are lacking. We conclude that targeted modulation of TNF-\u03b1 and IL-1\u2014particularly through locally delivered, appropriately timed agents used as an adjunct to conventional mechanical therapy\u2014is a biologically rational strategy.<\/jats:p>","DOI":"10.3390\/cimb48090889","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:33:32Z","timestamp":1788262412000},"page":"889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LPS-Induced TNF-\u03b1 and IL-1 Signaling in Periodontitis: Molecular Mechanisms and Therapeutic Opportunities"],"prefix":"10.3390","volume":"48","author":[{"given":"Maedeh","family":"Vakili Saatloo","sequence":"first","affiliation":[{"name":"Department of Periodontology, Boston University Henry M. Goldman School of Dental Medicine, 635 Albany Street, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Dibart","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Boston University Henry M. Goldman School of Dental Medicine, 635 Albany Street, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-3695","authenticated-orcid":false,"given":"Yun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Boston University Henry M. Goldman School of Dental Medicine, 635 Albany Street, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/jcpe.12732","article-title":"Impact of the global burden of periodontal diseases on health, nutrition and wellbeing of mankind: A call for global action","volume":"44","author":"Tonetti","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/0022034514552491","article-title":"Global burden of severe periodontitis in 1990\u20132010: A systematic review and meta-regression","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J. Dent. 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