Bear bile inhibits the immunosuppression activity of hepatic stellate cells in vivo.
OBJECTIVE
In the injured liver, hepatic stellate cells (HSCs) induce immunosuppression activity and thus participate in the pathogenesis of liver disease, including HCC. Therefore, finding new drugs to inhibit their immunosuppression activity is necessary. This study tests whether bear bile can affect the immunosuppression activities of HSCs.


METHODS
The mice were gavaged with bear bile for 4 weeks. The expression of HSCs was detected through desmin and ±-smooth muscle antibody immunohistochemistry. HSCs were isolated from these mice liver and then cultured with T cells in a mixed leukocyte reaction for 3 days. Stellate cell surface makers, T-cell apoptosis, regulatory T cells and the ability of T cells to kill hepatocellular carcinoma were determined via flow cytometry. Cytokines were determined by a mouse cytokine array panel and T-cell proliferation was determined through a BrdU kit.


RESULTS
Bear bile decreased HSCs and their surface molecules, and affected cytokine secretion. Interestingly, HSCs from the mice gavaged with bear bile promoted T-cell proliferation, inhibited T-cell apoptosis, decreased CD4+CD25+Foxp3+ regulatory T cells and enhanced the activation of T cells killing hepatocellular carcinoma.


CONCLUSIONS
Bear bile can inhibit the immunosuppression activity of HSCs and enhance immune response especial anti-tumor immune response.
Department of Hepatobiliary Surgery, Guizhou Province People's Hospital, Guizhou, China.
Chang-Sheng
CS
Zhou
Zhen-Yu
ZY
Yin
Wen-Xiu
WX
Zhao
Lei
L
Zhang
Jun-Yong
JY
You
Wei-Xue
WX
Su
Jia
J
Fan
Xiao-Min
XM
Wang
D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001646:Bile / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D001503:Ursidae
D000199:Actins; D016207:Cytokines; D003893:Desmin; C544013:alpha-smooth muscle actin, mouse