Morphological and molecular response of the MOCH‐1 oligodendrocyte cell line to serum and interferon‐γ: Possible implications for demyelinating disorders

Li, Y.; Atashi, Julie R.; Hayes, Carol; Reap, Elizabeth A.; Hunt, S.; Popko, Brian

doi:10.1002/jnr.490400207

Cited by 9 publications

(2 citation statements)

References 38 publications

(41 reference statements)

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“…Oligodendrocytes express receptors for IL‐2, IL‐1α/β, IFNγ, TNFα/β, IL6, and neurotrophins [ 47, 144–149]. Depending on the source of the oligodendrocytes (primary human, rodent, cow; cell lines), IL2 and IFNγ have been shown in vitro to be lethal [ 144, 231], to have no effect on cell viability [ 122, 144, 210], to induce proliferation [ 75, 144] or to alter cell phenotype or perturb function without being toxic [ 1, 105, 210] ( Table 1). Likewise, after dozens of studies, there are as many reports demonstrating TNFα to be toxic as there are showing it to be non‐toxic or even supportive in oligodendrocyte cultures [ 122, 126, 210, 231] ( Table 1).…”

Section: Immunologically Mediated Myelin Damage and Oligodendrocyte Dmentioning

confidence: 99%

Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease

Merrill

Scolding

1999

Neuropathology Appl Neurobio

101

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Oligodendrocytes synthesize and maintain myelin in the central nervous system (CNS). Damage may occur to these cells in a number of conditions, including infections, exposure to toxins, injury, degeneration, or autoimmune disease, arising both in the course of human disease and in experimental animal models of demyelination and dysmyelination; multiple sclerosis is the commonest human demyelinating disorder. Conventional classical accounts of the pathology of this and other myelin diseases have given great insights into their core features, but there remain considerable uncertainties concerning the timing, means and cause(s) of oligodendrocyte and myelin damage. At present, therapeutic efforts largely concentrate on immune manipulation and damage limitation, an approach that has produced only modest effects in multiple sclerosis. One reason for this must be the limited understanding of the mechanisms underlying cell damage - clearly, successful therapeutic strategies for preserving the oligodendrocyte-myelin unit must depend on knowledge of how oligodendrocyte damage and death occurs. In this review, mechanisms of oligodendrocyte and myelin damage are considered, and attempts made to relate them to disease processes, clinical and experimental. The hallmarks of different cell death processes are described, and oligodendrocyte-myelin injury by cellular and soluble mediators is discussed, both in vitro and invivo. Recent developments concerning the pathological involvement of oligodendrocytes in neurodegenerative disease are summarized. Finally, these neuropathological and applied neurobiological observations are drawn together in the context of multiple sclerosis.

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Section: Immunologically Mediated Myelin Damage and Oligodendrocyte Dmentioning

confidence: 99%

Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease

Merrill

Scolding

1999

Neuropathology Appl Neurobio

101

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“…I), which have been shown to express IFN-7 receptors (Torres et al, 1995). We have examined the effects of IFN-7 on oligodendrocytes using the MOCH-1 cell line, which was derived from an oligodendroglioma that developed in a transgenic line of mice and expresses a variety of features of oligodendrocytes (Hayes et al, 1992;Li et aL, 1995 Popko et al, 1994). Furthermore, these cells are immunoreactive against antibodies to galactocerebroside, a glycolipid marker of mature oligodendrocytes, and abundantly express myelin protein genes (Hayes et al, 1992).…”

Section: Cellular Sites Of Ifn-y Action In Immune-mediated Demyelinationmentioning

confidence: 99%

The effects of interferon-γ on the central nervous system

et al. 1997

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Interferon-gamma (IFN-gamma) is a pleotropic cytokine released by T-lymphocytes and natural killer cells. Normally, these cells do not traverse the blood-brain barrier at appreciable levels and, as such, IFN-gamma is generally undetectable within the central nervous system (CNS). Nevertheless, in response to CNS infections, as well as during certain disorders in which the CNS is affected, T-cell traffic across the blood-brain barrier increases considerably, thereby exposing neuronal and glial cells to the potent effects of IFN-gamma. A larger portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-gamma plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Moreover, the biochemical and physiological effects of IFN-gamma are discussed in the context of the potential consequences of such activities on the developing and mature nervous systems.

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Major histocompatibility complex heavy chain accumulation in the endoplasmic reticulum of oligodendrocytes results in myelin abnormalities

Baerwald

Corbin

Popko

2000

Journal of Neuroscience Research

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The immune cytokine interferon-gamma (IFN-gamma) is believed to be a key agent in the pathogenesis of immune-mediated demyelinating disorders. We have examined the possibility that one effect of this cytokine involves overloading the endoplasmic reticulum (ER) of oligodendrocytes through the induction of major histocompatibility complex (MHC) class I heavy chain (HC) gene expression. For these studies, we have utilized several genetic mouse models that yield different subcellular localizations of HC in oligodendrocytes. We show that transgenic mice that ectopically express HC in oligodendrocytes (MBP/MHC class I mice) fail to transport HC past the ER. These mice are hypomyelinated and have a tremoring phenotype. When oligodendrocytes deficient in beta-2 microglobulin (beta2m), which is required for MHC class I assembly and transport, were treated with IFN-gamma in vitro, HC was transported past the ER to the trans-Golgi network but not onto the cell surface. When an asymptomatic line of mice that expresses MHC class I in the CNS due to transgene-derived IFN-gamma (MBP/IFN-gamma mice) was crossed onto the beta2m-/- background, the resulting mice were asymptomatic. In contrast, increasing the amount of MHC class I protein transported through the ER in MBP/MHC class I transgenic mice, by crossing them to the asymptomatic MBP/IFN-gamma mice, exacerbated their phenotype. Taken together, these data indicate that the ER is a sensitive site in oligodendrocytes for accumulation of MHC class I HC and suggest a molecular mechanism for IFN-gamma's deleterious effects on these cells.

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Morphological and molecular response of the MOCH‐1 oligodendrocyte cell line to serum and interferon‐γ: Possible implications for demyelinating disorders

Cited by 9 publications

References 38 publications

Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease

Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease

The effects of interferon-γ on the central nervous system

Major histocompatibility complex heavy chain accumulation in the endoplasmic reticulum of oligodendrocytes results in myelin abnormalities

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