Developing and mature oligodendrocytes respond differently to the immune cytokine interferon-gamma.
Increasing evidence suggests that the immune cytokine interferon-gamma (IFN-gamma) plays a deleterious role in immune-mediated demyelinating disorders. To further understand the effects of IFN-gamma on oligodendrocytes, we have compared and quantitated the response of developing and mature oligodendrocytes in vitro to IFN-gamma and have observed several differences. Morphological changes and cell death occurred in developing cultures after 2 days in IFN-gamma, and in mature oligodendrocytes after 4-7 days. Developing oligodendrocytes underwent significantly increased apoptotic cell death in the presence of IFN-gamma, but mature oligodendrocytes exposed to IFN-gamma died of necrosis. Prior to morphological changes or cell death in mature oligodendrocytes exposed to IFN-gamma, steady-state levels of myelin-specific mRNAs and proteins were reduced. Thus, these results indicate that the sensitivity of oligodendrocytes to IFN-gamma is related to the developmental state of the cell. Such information is crucial for understanding the response of oligodendrocytes in immune-mediated demyelinating disorders and during remyelination in these diseases.
Baerwald
K D
KD
Neuroscience Center, University of North Carolina, Chapel Hill 27599-7250, USA.
Popko
B
B
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology; D009336:Necrosis; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D051381:Rats
D007371:Interferon-gamma