論文

査読有り 筆頭著者 国際誌
2019年1月

Serum Amyloid A Contributes to Chronic Apical Periodontitis via TLR2 and TLR4.

Journal of dental research
  • K Hirai
  • ,
  • H Furusho
  • ,
  • N Kawashima
  • ,
  • S Xu
  • ,
  • M C de Beer
  • ,
  • R Battaglino
  • ,
  • T Van Dyke
  • ,
  • P Stashenko
  • ,
  • H Sasaki

98
1
開始ページ
117
終了ページ
125
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1177/0022034518796456

In the current concept of bacterial infections, pathogen-associated molecular patterns (PAMPs) derived from pathogens and damage-associated molecular patterns (DAMPs) released from damaged/necrotic host cells are crucial factors in induction of innate immune responses. However, the implication of DAMPs in apical and marginal periodontitis is unknown. Serum amyloid A (SAA) is a DAMP that is involved in the development of various chronic inflammatory diseases, such as rheumatoid arthritis. In the present study, we tested whether SAA is involved in the pathogenesis of periapical lesions, using human periapical surgical specimens and mice deficient in SAA and Toll-like receptors (TLR). SAA1/2 was locally expressed in human periapical lesions at the mRNA and protein levels. The level of SAA protein appeared to be positively associated with the inflammatory status of the lesions. In the development of mouse periapical inflammation, SAA1.1/2.1 was elevated locally and systemically in wild-type (WT) mice. Although SAA1.1/2.1 double-knockout and SAA3 knockout mice had redundant attenuation of the extent of periapical lesions, these animals showed strikingly improved inflammatory cell infiltration versus WT. Recombinant human SAA1 (rhSAA1) directly induced chemotaxis of WT neutrophils in a dose-dependent manner in vitro. In addition, rhSAA1 stimulation significantly prolonged the survival of WT neutrophils as compared with nonstimulated neutrophils. Furthermore, rhSAA1 activated the NF-κB pathway and subsequent IL-1α production in macrophages in a dose-dependent manner. However, TLR2/TLR4 double deficiency substantially diminished these SAA-mediated proinflammatory responses. Taken together, the SAA-TLR axis plays an important role in the chronicity of periapical inflammation via induction of inflammatory cell infiltration and prolonged cell survival. The interactions of PAMPs and DAMPs require further investigation in dental/oral inflammation.

リンク情報
DOI
https://doi.org/10.1177/0022034518796456
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30189157
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304714
ID情報
  • DOI : 10.1177/0022034518796456
  • PubMed ID : 30189157
  • PubMed Central 記事ID : PMC6304714

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