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The interleukin-10 knockout mouse is highly susceptible to Porphyromonas gingivalis-induced alveolar bone loss.

AbstractOBJECTIVE:
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-1alpha and tumor necrosis factor alpha (TNF-alpha) were not up-regulated in gingival tissues by P. gingivalis-infection. Although interleukin-1beta 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 (IFNgamma), interleukin-6, interleukin-4, and prostaglandin E2 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.
AuthorsHajime Sasaki, Yoshimasa Okamatsu, Toshihisa Kawai, Ralph Kent, Martin Taubman, Philip Stashenko
JournalJournal of periodontal research (J Periodontal Res) Vol. 39 Issue 6 Pg. 432-41 (Dec 2004) ISSN: 0022-3484 [Print] United States
PMID15491348 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Copyright(c)Blackwell Munksgaard 2004
Chemical References
  • CD40 Antigens
  • Carrier Proteins
  • Interleukin-1
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Interleukin-10
Topics
  • Alveolar Bone Loss (microbiology)
  • Analysis of Variance
  • Animals
  • Apoptosis
  • CD40 Antigens (biosynthesis)
  • Carrier Proteins (biosynthesis)
  • Disease Models, Animal
  • Gene Expression
  • Genetic Predisposition to Disease
  • Interleukin-1 (antagonists & inhibitors)
  • Interleukin-10 (deficiency, genetics, physiology)
  • Membrane Glycoproteins (biosynthesis)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Porphyromonas gingivalis (pathogenicity)
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Specific Pathogen-Free Organisms
  • Up-Regulation

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