Morphological and molecular response of the MOCH-1 oligodendrocyte cell line to serum and interferon-gamma: possible implications for demyelinating disorders

The regional loss of oligodendrocytes is thought to be an important pathological event in a variety of demyelinating diseases of the central nervous system (CNS). Various components of serum, which are normally excluded from the CNS by the blood-brain barrier, have been implicated as mediators of demyelinating disorders. We have examined the effects of high concentrations of serum (10% fetal bovine serum, FBS), as well as the cytokine interferon-gamma (IFN-gamma), on an oligodendrocyte cell line, MOCH-1 cells. These cells changed from phase-bright, small round cells with multiple thin, branched processes in 1% FBS medium to flat, fibroblast-like cells with large cell bodies when cultured in 10% FBS medium or 1% FBS medium containing IFN-gamma. These morphological changes were accompanied by a large increase in expression of the astrocyte marker, glial fibrillary acidic protein (GFAP), as detected by Northern and Western blot analyses. In addition, Northern blot and fluorescence-activated cell sorting analyses revealed that IFN-gamma induced a very large increase in major histocompatibility complex (MHC) class I expression in MOCH-1 cells. MHC class II mRNA induction by IFN-gamma was also seen. In contrast, 10% FBS did not elevate either MHC class I or class II mRNA levels in MOCH-1 cells. The morphological and molecular effects of 10% FBS and IFN-gamma were reversible. We suggest that the response of MOCH-1 cells to high concentrations of serum and IFN-gamma may reflect an important in vivo response to oligodendrocytes to perturbations that occur in demyelinating disorders.