IL-33 exacerbates periodontal disease through induction of RANKL

J. Malcolm, R. A. Awang, J. Oliver-Bell, J. P. Butcher, L. Campbell, A. Adrados Planell, D. F. Lappin, S. Y. Fukada, C. J. Nile, F. Y. Liew, S. Culshaw

Research output: Contribution to journalArticle

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 kappa B 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.
Original languageEnglish
Pages (from-to)968-975
JournalJournal of Dental Research
Volume94
Issue number7
DOIs
Publication statusPublished - Jul 2015
Externally publishedYes

Keywords

  • ST2
  • Porphyromonas gingivalis
  • cytokines
  • gingiva
  • periodontitis
  • OPG

Cite this

Malcolm, J., Awang, R. A., Oliver-Bell, J., Butcher, J. P., Campbell, L., Adrados Planell, A., ... Culshaw, S. (2015). IL-33 exacerbates periodontal disease through induction of RANKL. Journal of Dental Research, 94(7), 968-975. https://doi.org/10.1177/0022034515577815
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. ; Culshaw, S. / IL-33 exacerbates periodontal disease through induction of RANKL. In: Journal of Dental Research. 2015 ; Vol. 94, No. 7. pp. 968-975.
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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 kappa B 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.",
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Malcolm, J, Awang, RA, Oliver-Bell, J, Butcher, JP, Campbell, L, Adrados Planell, A, Lappin, DF, Fukada, SY, Nile, CJ, Liew, FY & Culshaw, S 2015, 'IL-33 exacerbates periodontal disease through induction of RANKL' Journal of Dental Research, vol. 94, no. 7, pp. 968-975. https://doi.org/10.1177/0022034515577815

IL-33 exacerbates periodontal disease through induction of RANKL. / 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.; Culshaw, S.

In: Journal of Dental Research, Vol. 94, No. 7, 07.2015, p. 968-975.

Research output: Contribution to journalArticle

TY - JOUR

T1 - IL-33 exacerbates periodontal disease through induction of RANKL

AU - Malcolm, J.

AU - Awang, R. A.

AU - Oliver-Bell, J.

AU - Butcher, J. P.

AU - Campbell, L.

AU - Adrados Planell, A.

AU - Lappin, D. F.

AU - Fukada, S. Y.

AU - Nile, C. J.

AU - Liew, F. Y.

AU - Culshaw, S.

PY - 2015/7

Y1 - 2015/7

N2 - 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 kappa B 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.

AB - 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 kappa B 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.

KW - ST2

KW - Porphyromonas gingivalis

KW - cytokines

KW - gingiva

KW - periodontitis

KW - OPG

U2 - 10.1177/0022034515577815

DO - 10.1177/0022034515577815

M3 - Article

VL - 94

SP - 968

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JO - Journal of Dental Research

JF - Journal of Dental Research

SN - 0022-0345

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Malcolm J, Awang RA, Oliver-Bell J, Butcher JP, Campbell L, Adrados Planell A et al. IL-33 exacerbates periodontal disease through induction of RANKL. Journal of Dental Research. 2015 Jul;94(7):968-975. https://doi.org/10.1177/0022034515577815