Hepatitis B core antigen regulates dendritic cell proliferation and apoptosis through regulation of PKC/NF‑κB signaling pathway.

Hepatitis B core antigen (HBcAg) possesses unusual immunologic features. However, the biological roles and mechanisms of HBcAg in dendritic cell proliferation and apoptosis remain to be elucidated. In the present study, DC2.4 cells were treated with different concentrations of HBcAg (10, 20 and 30 mu g/ml). MTT assay and flow cytometry (Annexin V/propidium iodide analysis) were performed to investigate changes in cell proliferation and apoptosis. Western blot analysis was conducted to examine the changes in nuclear factor (NF)-B and protein kinase C (PKC) signaling pathways. NF-B inhibitor pyrrolidine dithiocarbamate (PDTC) and PKC inhibitor Chelerythrine were used to block these two signaling pathways. It was identified that HBcAg increased proliferation and decreased apoptosis in a dose-dependent manner. Western blotting results demonstrated that HBcAg upregulated p-PKC, p-IB, p-P65, tumor necrosis factor- and B-cell lymphoma 2 (Bcl-2) levels, and downregulated cleaved caspase 3, demonstrating that HBcAg activated the PKC and NF-B signaling pathways. NF-B inhibitor PDTC reduced the effects of HBcAg on DC2.4 proliferation (0.6 fold vs. 0.25 fold) and apoptosis (0.43 fold vs. 0.17 fold), and on Bcl-2 expression levels. PKC inhibitor Chelerythrine reduced the biological effects of HBcAg; it reduced proliferation (0.67 fold vs. 0.23 fold) and upregulated apoptosis (0.43 fold vs. 0.13 fold). Chelerythrine also blocked NF-B activity and the HBcAg-induced Bcl-2 increase, suggesting the effect on Bcl-2 from HBcAg was dependent on the PKC/NF-B signaling pathway. In conclusion, HBcAg promoted proliferation and inhibited apoptosis through the PKC/NF-B/Bcl-2 signaling pathway in DC2.4 cells.