Hepatitis B core antigen regulates dendritic cell proliferation and apoptosis through regulation of PKC/NFκB signaling pathway.
Mol Med Rep
; 18(6): 5726-5732, 2018 Dec.
Article
en En
| MEDLINE
| ID: mdl-30365118
ABSTRACT
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 µg/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)κB and protein kinase C (PKC) signaling pathways. NFκB 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 dosedependent manner. Western blotting results demonstrated that HBcAg upregulated pPKC, pIκB, pP65, tumor necrosis factorα and Bcell lymphoma 2 (Bcl2) levels, and downregulated cleaved caspase 3, demonstrating that HBcAg activated the PKC and NFκB signaling pathways. NFκB 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 Bcl2 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 NFκB activity and the HBcAginduced Bcl2 increase, suggesting the effect on Bcl2 from HBcAg was dependent on the PKC/NFκB signaling pathway. In conclusion, HBcAg promoted proliferation and inhibited apoptosis through the PKC/NFκB/Bcl2 signaling pathway in DC2.4 cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Proteína Quinasa C
/
Transducción de Señal
/
FN-kappa B
/
Apoptosis
/
Antígenos del Núcleo de la Hepatitis B
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2018
Tipo del documento:
Article