Interferon beta affects retinal pigment epithelial cell proliferation via protein kinase C pathways.
BACKGROUND
The aim of this study is to see the effect of interferon beta (IFN-beta) 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-beta, 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-beta were assessed by (3)H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-beta and calphostin C was also measured.


RESULTS
IFN-beta 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 (3)H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-beta had no inhibitory or stimulatory effect on (3)H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-beta exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h.


CONCLUSIONS
IFN-beta inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.
Qiao
H
H
Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Sakamoto
T
T
Hinton
D R
DR
Gopalakrishna
R
R
Ishibashi
T
T
Ryan
S J
SJ
Inomata
H
H
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D016899:Interferon-beta; D011493:Protein Kinase C; C058819:calphostin C