Overexpression of LDOC1 in human biliary epithelial cells inhibits apoptosis through NF-κB signaling.

OBJECTIVES

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.