Counteracting effect of IFN-beta on IFN-gamma-induced proliferation of human astrocytes in culture.
Recent clinical trials have shown that interferon beta (IFN-beta) is effective in reducing exacerbations in relapsing-remitting MS, while interferon gamma (IFN-gamma) precipitates the relapses. To investigate mechanisms underlying the beneficial effects of IFN-beta and the detrimental effects of IFN-gamma in MS, cell growth-regulatory effects of IFNs were examined in astrocyte-enriched cultures isolated from fetal brains of 12-20 weeks' gestation. Treatment with IFN-gamma (50 or 500 IU ml-1) stimulated significantly the proliferation of astrocytes in 6 out of 9 culture series examined, while IFN-beta (50 or 500 IU ml-1) inhibited the astrocytic proliferation in 3 out of 9 cultures, and IFN-alpha (50 or 500 IU ml-1) did not affect the proliferation IFN-beta and to a lesser degree IFN-alpha reduced the astrocytic proliferation induced by IFN-gamma-treatment in 8 out of 9 culture series. The counteracting effect of IFN-alpha/IFN-beta against IFN-gamma-induced astrocytic proliferation was verified by the DNA content distribution analysis of propidium iodide-labeled cells. The antagonistic effect of IFN-alpha/IFN-beta on the growth-promoting activity of IFN-gamma in cultured human astrocytes suggests that interferons serve as growth regulators of astrocytes at sites of reactive gliosis lesions of MS.
Satoh
J
J
Department of Medicine, University of British Columbia, Vancouver, Canada.
Paty
D W
DW
Kim
S U
SU
D001253:Astrocytes / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
D018809:Proliferating Cell Nuclear Antigen; D016899:Interferon-beta; D007371:Interferon-gamma; D004247:DNA