TY - JOUR
T1 - Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells
AU - Susilowati, Heni
AU - Okamura, Hirohiko
AU - Hirota, Katsuhiko
AU - Shono, Masayuki
AU - Yoshida, Kaya
AU - Murakami, Keiji
AU - Tabata, Atsushi
AU - Nagamune, Hideaki
AU - Haneji, Tatsuji
AU - Miyake, Yoichiro
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research No. 21592387 from The Ministry of Education, Science, Sport, and Culture of Japan. We thank Naomi Shinohara and Eiko Sasaki for technical assistances.
PY - 2011/1/7
Y1 - 2011/1/7
N2 - 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.
AB - 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.
KW - Calcineurin
KW - Calcium
KW - Intermedilysin
KW - Intrahepatic bile duct cells
KW - NFAT
KW - Streptococcus intermedius
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U2 - 10.1016/j.bbrc.2010.11.057
DO - 10.1016/j.bbrc.2010.11.057
M3 - Article
C2 - 21094139
AN - SCOPUS:78650872240
SN - 0006-291X
VL - 404
SP - 57
EP - 61
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -