Intracellular B7-H4 suppresses bile duct epithelial cell apoptosis in human primary biliary cirrhosis.
The expression and function of B7-H4, a recently identified co-inhibitory molecule of the B7 superfamily, in the pathogenesis of primary biliary cirrhosis (PBC) is still unclear. Here the expression of B7-H4 in sections from PBC patients (n = 16) was examined by immunohistochemistry and it was detected in primary bile duct epithelial cells (BECs) which were isolated from PBC patients by flow cytometry (FACs). Moreover, we also analyzed BECs-associated B7-H4 function through knock-down of its expression via RNA interference (RNAi) in vitro. Immunohistochemistry and FACs evidenced that the expression of B7-H4 was restricted in the cytoplasm of BECs from PBC patients, while it was completely absent in normal liver tissues. The cytoplasmic B7-H4 gene was cloned, and sequenced analysis showed it was encoded by the same gene to the membrane B7-H4. Interesting, silencing B7-H4 by specific RNAi resulted in enhanced FasL expression and BEC apoptosis. Conversely, interruption of Fas\FasL interaction with using FasL blocking antibodies (clone 4H9) reversed cell apoptosis. Our results suggested that the intracellular B7-H4 appears to prevent Fas/FasL-mediated BEC apoptosis during the progression of PBC, and indicates B7-H4 is a possible target for therapeutic intervention of this disease.
Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, People's Republic of China.
Yongwen
Y
Chen
Guoning
G
Guo
Sheng
S
Guo
Shinji
S
Shimoda
Kenneth R
KR
Shroyer
Yuyu
Y
Tang
Yuzhang
Y
Wu
D017209:Apoptosis; D001652:Bile Ducts / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology*; D053222:Fas Ligand Protein; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000473:pathology*; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019014:fas Receptor
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; D019014:fas Receptor