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Increased interleukin-18 in the gingival tissues evokes chronic periodontitis after bacterial infection.

Abstract
Periodontal disease is a chronic inflammatory disease that results in the breakdown of the tooth-supporting tissues, and can ultimately lead to resorption of the alveolar bone. Recently, several studies have shown a close relationship between increased interleukin-18 (IL-18) levels and the pathogenesis of chronic periodontitis, a major cause of tooth loss. However, it has yet to be shown whether chronic periodontitis results from or causes an increase in IL-18 after bacterial infection. In the present study, we investigated how IL-18 overexpression relates to periodontal disease using IL-18 transgenic (Tg) mice. IL-18Tg and wild-type mice were inoculated intraorally with Porphyromonas (P.) gingivalis, which has been implicated in the etiology of chronic periodontitis. Seventy days after P. gingivalis infection, alveolar bone loss and gingival cytokine levels were assessed using histo-morphological analysis and enzyme-linked immuno-absorbent assay, respectively. Periodontal bone loss was evoked in IL-18Tg mice, but not in wild-type mice. Interestingly, levels of bone-resorptive cytokines, including IL-1α, IL-1β, tumor necrosis factor-α, and IL-6, were unchanged in the gingival tissues of IL-18Tg mice infected with P. gingivalis, although levels of interferon γ (a proinflammatory T-helper 1 cytokine) decreased. RT-PCR analysis showed elevated expression of mRNAs for receptor activator of nuclear factor kappa-B ligand (a key stimulator of osteoclast development and activation) and CD40 ligand (a marker of T cell activation) in the gingiva of IL-18Tg mice infected with P. gingivalis. We conclude that increased IL-18 in the gingival tissues evokes chronic periodontitis after bacterial infection, presumably via a T cell-mediated pathway.
AuthorsKotaro Yoshinaka, Noriaki Shoji, Takashi Nishioka, Yumiko Sugawara, Tomoaki Hoshino, Shunji Sugawara, Takashi Sasano
JournalThe Tohoku journal of experimental medicine (Tohoku J Exp Med) Vol. 232 Issue 3 Pg. 215-22 (03 2014) ISSN: 1349-3329 [Electronic] Japan
PMID24646956 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Interleukin-18
Topics
  • Alveolar Bone Loss (blood, complications, microbiology, pathology)
  • Animals
  • Bacterial Infections (blood, complications, metabolism, microbiology)
  • Biomarkers (metabolism)
  • Chronic Periodontitis (blood, etiology, metabolism, microbiology)
  • Gingiva (metabolism, microbiology, pathology)
  • Interleukin-18 (blood, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Porphyromonas gingivalis (physiology)
  • Th1 Cells (metabolism)
  • Th2 Cells (metabolism)
  • Transgenes

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