IL-33 Exacerbates Periodontal Disease through Induction of RANKL

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of dental research 2015-07, Vol.94 (7), p.968-975
Main 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., Culshaw, S.
Format: Article
Language:English
Subjects:
Alveolar bone
Alveolar Bone Loss - immunology
Alveolar Bone Loss - microbiology
Alveolar Bone Loss - pathology
Alveolar Process - pathology
Animal models
Animals
Antibodies, Bacterial - blood
Arthritis
B-Lymphocytes - immunology
Bacteria
Bacteroidaceae Infections - immunology
Bone loss
Chronic Periodontitis - immunology
Chronic Periodontitis - microbiology
Collagen
Disease
Disease Models, Animal
Female
Gene expression
Genetic engineering
Gingiva
Gingiva - immunology
Gum disease
Humans
Immunoglobulin G - blood
Interleukin-1 Receptor-Like 1 Protein
Interleukin-33
Interleukins - analysis
Interleukins - antagonists & inhibitors
Interleukins - immunology
Interleukins - pharmacology
Laboratories
Lymph nodes
Lymph Nodes - immunology
Lymphocytes
Lymphocytes - immunology
Lymphocytes B
Lymphocytes T
Maxilla - pathology
Mice
Mice, Inbred BALB C
Microbiota
Osteoprotegerin
Osteoprotegerin - pharmacology
Periodontal diseases
Periodontitis
Polymerase chain reaction
Porphyromonas gingivalis
Porphyromonas gingivalis - immunology
RANK Ligand - immunology
Receptors, Cell Surface - analysis
Receptors, Interleukin - antagonists & inhibitors
T-Lymphocytes - immunology
Therapeutic applications
TRANCE protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-0345
1544-0591
DOI:10.1177/0022034515577815