{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:29:09Z","timestamp":1791217749646,"version":"4.1.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T00:00:00Z","timestamp":1427241600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>Cytokines mediate the balance between protective and destructive immunity in periodontitis. We sought to investigate the role of IL-33 in periodontitis. The expression of IL-33 in gingival tissue from healthy controls ( n = 10) and patients with chronic periodontitis ( n = 17) was investigated. Based on a murine model of periodontal disease, the function of IL-33 was determined first by administration of exogenous IL-33 and second by inhibition of IL-33 signaling using mice deficient in the IL-33 receptor ST2. Alveolar bone level, serum antibody, and lymphocyte responses were assessed in the murine model. Expression of IL-33 and ST2 was elevated in gingival tissues from patients with chronic periodontitis as compared with healthy tissues ( P &lt; 0.05). Similarly, Il33 expression was higher in periodontal tissues of Porphyromonas gingivalis\u2013infected mice as compared with sham-infected controls ( P &lt; 0.05). IL-33 treatment of P. gingivalis\u2013infected mice significantly exacerbated alveolar bone loss when compared with infection or IL-33 treatment alone ( P &lt; 0.001). Conversely, P. gingivalis infection\u2013induced alveolar bone loss was attenuated in mice lacking ST2. The percentages of T and B lymphocytes expressing nuclear factor \u03baB ligand (RANKL) in the gingival tissues and T lymphocytes expressing RANKL in the cervical draining lymph nodes were higher in IL-33-treated P. gingivalis\u2013infected mice versus phosphate buffered saline\u2013treated P. gingivalis\u2013infected controls (all P &lt; 0.001). Targeting the RANKL pathway by osteoprotegerin administration abrogated periodontal bone destruction in P. gingivalis\u2013infected, IL-33-treated mice. These data demonstrate a previously unrecognized role for IL-33 in exacerbating bone loss in a RANKL-dependent manner in the context of bacterial infection and suggest that this pathway may be amenable to manipulation as a novel therapeutic target in periodontitis.<\/jats:p>","DOI":"10.1177\/0022034515577815","type":"journal-article","created":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T05:32:43Z","timestamp":1427347963000},"page":"968-975","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":74,"title":["IL-33 Exacerbates Periodontal Disease through Induction of RANKL"],"prefix":"10.1177","volume":"94","author":[{"given":"J.","family":"Malcolm","sequence":"first","affiliation":[{"name":"Institute of Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, 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