Bimodal effect of interferon-β on astrocyte proliferation and survival: Importance of nuclear factor-κB.
Accumulating evidence indicates that interferon-β (IFN-β) can modify the complex immunopathogenic scenario causing clinical relapse activity and disease progression in MS. However, the beneficial effects of IFN-β in MS patients may also depend on non-immune mechanisms, including the modulation of astrocyte function. In the present report, we have shown that, depending on the dose, IFN-β treatment can either promote astrocyte proliferation and survival, or result astrocyte death. These actions depend, at least in part, on the regulation of nuclear factor-kappa B (NF-κB), an inducible transcription factor present in neurons and glia. This bimodal effect of IFN-β adds a new layer of complexity in the actions of IFN-β within the CNS.
Barca
Olga
O
Departamento de Fisioloxía, Facultade de Medicina, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Devesa-Peleteiro
Pablo
P
Seoane
Marcos
M
Señarís
Rosa M A
RM
Arce
Víctor M
VM
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D018709:Statistics, Nonparametric
D000590:Amino Acid Chloromethyl Ketones; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D016328:NF-kappa B; C484771:benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone; D016899:Interferon-beta; D051058:Oncogene Protein v-akt; D001973:Bromodeoxyuridine