IL-33 exacerbates periodontal disease through induction of RANKL

Malcolm, J. et al. (2015) IL-33 exacerbates periodontal disease through induction of RANKL. Journal of Dental Research, 94(7), pp. 968-975. (doi:10.1177/0022034515577815) (PMID:25808546)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and Lappin, Dr David and Oliver-Bell, Dr Jessica and Butcher, Mr John and Malcolm, Dr Jennifer and Culshaw, Professor Shauna and Adrados Planell, Miss Ana and Nile, Dr Chris and Fukada, Dr Sandra
Authors: Malcolm, J., Awang, R.A., Oliver-Bell, J., Butcher, J.P., Campbell, L., Adrados Planell, A., Lappin, D.F., Fukada, S.Y., Nile, C.J., Liew, F.Y., and Culshaw, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Journal of Dental Research
ISSN:0022-0345
ISSN (Online):1544-0591

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
565531What is the role of Interleukin-33 in periodontal diseaseShauna CulshawRoyal College of Surgeons of Edinburgh (RCSE)SRG/11/046SM - DENTAL SCHOOL