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The interleukin‐10 knockout mouse is highly susceptible to Porphyromonas gingivalis ‐induced alveolar bone loss
Author(s) -
Sasaki Hajime,
Okamatsu Yoshimasa,
Kawai Toshihisa,
Kent Ralph,
Taubman Martin,
Stashenko Philip
Publication year - 2004
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2004.00760.x
Subject(s) - porphyromonas gingivalis , interleukin , dental alveolus , cytokine , bone resorption , tumor necrosis factor alpha , interleukin 6 , periodontitis , immunology , biology , chemistry , endocrinology , medicine , dentistry
Objective: Interleukin‐10 is an anti‐inflammatory cytokine that reduces periapical bone loss, but its role in periodontal bone loss is unclear. In the present study, we tested the hypothesis that endogenous interleukin‐10 is a potent suppressor of Porphyromonas gingivalis ‐induced alveolar bone loss in vivo . Methods: Interleukin‐10 knockout (–/–) and wild‐type mice were inoculated intraorally with P. gingivalis . Non‐infected animals served as negative controls. Alveolar bone loss, gingival cytokine levels, and gingival gene expression were assessed using morphometric analysis, enzyme‐linked immunosorbent assay (ELISA), and semiquantitative reverse transcription polymerase chain reaction (RT–PCR), respectively. Results: P. gingivalis ‐infected interleukin‐10 –/– mice exhibited severe alveolar bone loss compared to non‐infected interleukin‐10 –/– and wild‐type mice by day 42. Surprisingly, bone resorptive cytokines interleukin‐1α and tumor necrosis factor alpha (TNF‐α) were not up‐regulated in gingival tissues by P. gingivalis ‐infection. Although interleukin‐1β was marginally increased, blockade of both interleukin‐1 isoforms or interleukin‐1 receptor type I with neutralizing antisera failed to reduce alveolar bone loss in interleukin‐10 –/– mice, indicating the operation of an interleukin‐1‐independent mechanism. No strong correlations between bone loss and other cytokines was observed, although interferon gamma (IFNγ), interleukin‐6, interleukin‐4, and prostaglandin E 2 were modestly up‐regulated in infected interleukin‐10 –/– mice. P. gingivalis infection reduced the expression of cell markers in gingival tissue on days 7 and 14 in both interleukin‐10 –/– and wild‐type animals, suggestive of bacteria‐induced cytotoxicity or apoptosis. This was followed by up‐regulated expression of receptor activator of nuclear factor kappa B ligand (RANKL) and CD40 ligand (CD40L on days 28 and 70 in infected interleukin‐10 –/– mice only. Conclusion: The interleukin‐10 –/– mouse is highly susceptible to bone loss induced by the periodontal pathogen P. gingivalis , which is mediated via an interleukin‐1‐independent pathway.