Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells

Heni Susilowati, Hirohiko Okamura, Katsuhiko Hirota, Masayuki Shono, Kaya Yoshida, Keiji Murakami, Atsushi Tabata, Hideaki Nagamune, Tatsuji Haneji, Yoichiro Miyake

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellular calcium ([Ca2+]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-κB translocation in human hepatic HepG2 cells, ILY did not affect NF-κB localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca2+]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells.

Original languageEnglish
Pages (from-to)57-61
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - Jan 7 2011
Externally publishedYes


  • Calcineurin
  • Calcium
  • Intermedilysin
  • Intrahepatic bile duct cells
  • NFAT
  • Streptococcus intermedius

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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