論文

査読有り
2010年4月

Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation

LABORATORY INVESTIGATION
  • Ikuko Haruta
  • ,
  • Ken Kikuchi
  • ,
  • Etsuko Hashimoto
  • ,
  • Minoru Nakamura
  • ,
  • Hiroshi Miyakawa
  • ,
  • Katsuhiko Hirota
  • ,
  • Noriyuki Shibata
  • ,
  • Hidehito Kato
  • ,
  • Yutaka Arimura
  • ,
  • Yoichiro Kato
  • ,
  • Takehiko Uchiyama
  • ,
  • Hideaki Nagamune
  • ,
  • Makio Kobayashi
  • ,
  • Yoichiro Miyake
  • ,
  • Keiko Shiratori
  • ,
  • Junji Yagi

90
4
開始ページ
577
終了ページ
588
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/labinvest.2010.40
出版者・発行元
NATURE PUBLISHING GROUP

Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). We earlier reported that the bacterial lipoteichoic acid was detected at the sites of inflammation around damaged bile ducts in the livers of PBC, and PBC patients' sera showed high titers against streptococcal histone-like protein. Here, we investigated whether chronic bacterial exposure could trigger PBC-like epithelial cell damage in normal mouse. BALB/c mice were repeatedly inoculated with various bacteria for 8 weeks. At 1 week (Group 1) and 3, 4, or 20 months (long term; Group 2) after the final inoculation, mice were killed to obtain samples. In the livers of the Streptococcus intermedius (S.i.)-inoculated mice in Group 1, cellular infiltration was predominantly observed around the bile ducts over the hepatic parenchyma. In the S.i.-inoculated mice in Group 2, portal but not parenchymal inflammation was observed in the livers, and periductal cellular infiltrates were detected in the salivary glands. Both S. i.-inoculated Groups 1 and 2 BALB/c mice sera had antibodies against HuCCT1 biliary epithelial cells, anti-nuclear antibodies, and anti-gp210 antibodies, but not anti-mitochondrial antibodies. Immunoreactivity to histone-like DNA-binding protein of S.i. (S.i.-HLP) was detectable around the sites of chronic nonsuppurative destructive cholangitis in the portal area in the livers of both S. i.-inoculated Groups 1 and 2 BALB/c mice. Furthermore, anti-S.i.-HLP antibody bound to synthetic gp210 peptide, as well. Bacteria triggered PBC-like cholangitis, multifocal epithelial inflammation, and autoantibody production. Bacteria are likely involved in the pathogenesis of PBC and of associated multifocal epithelial inflammation. Laboratory Investigation (2010) 90, 577-588; doi: 10.1038/labinvest.2010.40; published online 8 February 2010

Web of Science ® 被引用回数 : 25

リンク情報
DOI
https://doi.org/10.1038/labinvest.2010.40
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20142809
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000276567800007&DestApp=WOS_CPL

エクスポート
BibTeX RIS