論文

査読有り
2015年8月25日

Necrosis-induced TLR3 activation promotes TLR2 expression in gingival cells

Journal of Dental Research
  • K. Mori
  • ,
  • M. Yanagita
  • ,
  • S. Hasegawa
  • ,
  • M. Kubota
  • ,
  • M. Yamashita
  • ,
  • S. Yamada
  • ,
  • M. Kitamura
  • ,
  • S. Murakami

94
8
開始ページ
1149
終了ページ
1157
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1177/0022034515589289
出版者・発行元
SAGE PUBLICATIONS INC

© International & American Associations for Dental Research. Damage-associated molecular patterns (DAMPs), endogenous molecules released from injured or dying cells, evoke sterile inflammation that is not induced by microbial pathogens. Periodontal diseases are infectious diseases caused by oral microorganisms; however, in some circumstances, DAMPs might initiate inflammatory responses before host cells recognize pathogen-associated molecular patterns. Here, we showed that the necrotic cell supernatant (NCS) functioned as an endogenous danger signal when released from necrotic epithelial cells exposed to repeat freeze thawing. The NCS contained RNA and stimulated the production of inflammatory cytokines interleukin 6 (IL-6) and IL-8 from gingival epithelial cells and gingival fibroblasts. Targeted knockdown of Toll-like receptor 3 (TLR3) in these cells significantly suppressed the ability of the NCS to induce IL-6 and IL-8 production. Epithelial cells and fibroblasts recognized the NCS from heterologous cells. Interestingly, the activation of TLR3, rather than other TLRs, induced TLR2 mRNA expression and proteins in gingival epithelial cells, and pretreatment with the NCS or polyinosinic:polycytidylic acid (Poly(I:C)), a strong TLR3 activator, enhanced inflammatory cytokine production induced by subsequent stimulation with Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide, a TLR2 agonist. Moreover, the NCS reduced the expression of epithelial tight junction molecules zona occludens 1 and occludin and increased the permeability of epithelial tight junctions. These findings suggest that endogenous danger signal molecules such as self-RNA released from necrotic cells are recognized by TLR3 and that a subsequent increase of TLR2 expression in periodontal compartments such as gingival epithelial cells and gingival fibroblasts may enhance the inflammatory response to periodontopathic microbes recognized by TLR2 such as P. gingivalis, which also disrupts epithelial barrier functions. Thus, DAMPs may be involved in the development and prolongation of periodontal disease.

リンク情報
DOI
https://doi.org/10.1177/0022034515589289
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26045329
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000358182000019&DestApp=WOS_CPL
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84937872307&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84937872307&origin=inward
ID情報
  • DOI : 10.1177/0022034515589289
  • ISSN : 0022-0345
  • eISSN : 1544-0591
  • PubMed ID : 26045329
  • SCOPUS ID : 84937872307
  • Web of Science ID : WOS:000358182000019

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