Overexpression of LDOC1 in human biliary epithelial cells inhibits apoptosis through NF-κB signaling.
OBJECTIVE
Biliary atresia (BA) is a devastating pediatric cholestatic liver disease. Increasing evidence indicates that nuclear factor (NF)-κB signaling plays a key role in the pathogenesis of BA. Leucine zipper downregulated in cancer 1 (LDOC1) may control the expression of NF-κB. The aim of this study was to evaluate the relation between LDOC1 and inflammation/apoptosis mediated by NF-κB in the human intrahepatic biliary epithelial cells (HIBECs).


METHODS
HIBECs were divided into 3 treatment groups: control, mock transfection group, and LDOC1 transfection. Immunofluorescence, reverse transcription polymerase chain reaction, Western blot, and flow cytometry analysis were used to investigate the effectiveness of LDOC1-transfected HIBECs and the expression of NF-κB. Apoptosis was detected by Hochest/ propidium iodide staining. Interleukin (IL)-2 and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay.


RESULTS
The expression of NF-κB was higher in the LDOC1-transfected group when compared with the control and mock-transfected groups as evaluated by immunofluorescence, reverese transcription polymerase chain reaction, and Western blot analysis. The rate of apoptosis was significantly lower in the LDOC1-transfected group when compared with the control and mock-transfected groups. The levels of IL-2 and TNF-α were significantly higher in the LDOC1-transfected group when compared with the control and mock-transfected groups.


CONCLUSIONS
Upregulation of LDOC1 in HIBEC increases the expression of NF-κB, which may promote the activation of IL-2 and TNF-α secretion and inhibit cell apoptosis.
Department of Pediatric Surgery, Children's Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China.
Zai
Z
Song
Rui
R
Dong
Rui
R
Zhao
Shan
S
Zheng
D017209:Apoptosis; D001656:Biliary Atresia / Q000378:metabolism* / Q000473:pathology; D001659:Biliary Tract / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D007376:Interleukin-2; C120625:LDOC1 protein, human; D016328:NF-kappa B; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins