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IL-33 exacerbates periodontal disease through induction of RANKL

Lookup NU author(s): Dr Christopher NileORCiD

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Abstract

© International & American Associations for Dental Research 2015.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 < 0.05). Similarly, Il33 expression was higher in periodontal tissues of Porphyromonas gingivalis-infected mice as compared with sham-infected controls (P < 0.05). IL-33 treatment of P. gingivalis-infected mice significantly exacerbated alveolar bone loss when compared with infection or IL-33 treatment alone (P < 0.001). Conversely, P. gingivalis infection-induced alveolar bone loss was attenuated in mice lacking ST2. The percentages of T and B lymphocytes expressing nuclear factor κB 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-infected mice versus phosphate buffered saline-treated P. gingivalis-infected controls (all P < 0.001). Targeting the RANKL pathway by osteoprotegerin administration abrogated periodontal bone destruction in P. gingivalis-infected, 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.

Publication metadata

Author(s): Malcolm J, Awang RA, Oliver-Bell J, Butcher JP, Campbell L, Adrados Planell A, Lappin DF, Fukada SY, Nile CJ, Liew FY, Culshaw S

Publication type: Article

Publication status: Published

Journal: Journal of Dental Research

Year: 2015

Volume: 94

Issue: 7

Pages: 968-975

Print publication date: 01/07/2015

Online publication date: 25/03/2015

Acceptance date: 02/04/2015

ISSN (print): 0022-0345

ISSN (electronic): 1544-0591

Publisher: SAGE Publications Inc.

URL: https://doi.org/10.1177/0022034515577815

DOI: 10.1177/0022034515577815

PubMed id: 25808546

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