Interferon β Affects Retinal Pigment Epithelial Cell Proliferation via Protein Kinase C Pathways

Abstract

Background: The aim of this study is to see the effect of interferon β (IFN-β) on cell proliferation and the protein kinase C (PKC) signaling pathway. Methods: Proliferation of cultured human retinal pigment epithelium (RPE) cells, with various concentrations of IFN-β, and with or without 3% fetal calf serum (FCS), was assessed by cell counting. Effects of short (3 h) or prolonged (48 h) exposure of RPE cells to natural human IFN-β were assessed by ³H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-β and calphostin C was also measured. Results: IFN-β inhibited the increased proliferation by FCS in the prolonged-exposure assay. The PKC inhibitor calphostin C also showed an inhibitory effect on RPE cell growth and ³H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-β had no inhibitory or stimulatory effect on ³H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-β exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h. Conclusion: IFN-β inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.