Glial Cell Mitogens bFGF and PDGF Differentially Regulate Development of O4+GalC- Oligodendrocyte Progenitors

Gard, Anthony L.; Pfeiffer, S. E.

doi:10.1006/dbio.1993.1269

Cited by 167 publications

(120 citation statements)

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“…Contrary to previous findings on O-2A/OPCs demonstrating IFNγ enhances toxicity to TNFα, 3 we found that IFNγ protects committed oligodendrocytes (defined by galactocerebroside (GalC) expression [22][23][24][25] ) from TNFα ( Figure 1). In cultures of 499.5% GalC + oligodendrocytes, TNFα exposure caused concentration-dependent cell death within 72 h. Significant cell death was observed with 0.1 ng/ml TNFα ( Figure 1a; 44 ± 1.6% to 77 ± 1.8% cell death at 0.1-100 ng/ml, respectively).…”

Section: Resultscontrasting

confidence: 99%

cFLIP is critical for oligodendrocyte protection from inflammation

et al. 2015

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Neuroinflammation associated with degenerative central nervous system disease and injury frequently results in oligodendrocyte death. While promoting oligodendrocyte viability is a major therapeutic goal, little is known about protective signaling strategies. We report that in highly purified rat oligodendrocytes, interferon gamma (IFNγ) activates a signaling pathway that protects these cells from tumor necrosis factor alpha (TNFα)-induced cytotoxicity. IFNγ protection requires Jak (Janus kinase) activation, components of the integrated stress response and NF-κB activation. Although NF-κB activation also occurred transiently in the absence of IFNγ and presence of TNFα, this activation was not sufficient to prevent induction of the TNFα-responsive cell death pathway. Genetic inhibition of NF-κB translocation to the nucleus abrogated IFNγ-mediated protection and did not change the cell death induced by TNFα, suggesting that NF-κB activation via IFNγ induces a different set of responses than activation of NF-κB via TNFα. A promising candidate is the NF-κB target cFLIP (cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein), which is protease-deficient caspase homolog that inhibits caspase-3 activation. We show that IFNγ-mediated protection led to upregulation of cFLIP. Overexpression of cFLIP was sufficient for oligodendrocyte protection from TNFα and short hairpin RNA knockdown of cFLIP-abrogated IFNγ -mediated protection. To determine the relevance of our in vitro finding to the more complex in vivo situation, we determined the impact on oligodendrocyte death of regional cFLIP loss of function in a murine model of neuroinflammation. Our data show that downregulation of cFLIP during inflammation leads to death of oligodendrocytes and decrease of myelin in vivo. Taken together, we show that IFNγ-mediated induction of cFLIP expression provides a new mechanism by which this cytokine can protect oligodendrocytes from TNFα-induced cell death.

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Section: Resultscontrasting

confidence: 99%

cFLIP is critical for oligodendrocyte protection from inflammation

et al. 2015

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“…Simple methods for the isolation and purification of workable quantities of OPCs not only aid in efforts to better understand oligodendrocyte development, function and axonoligodendroglial interactions but also provide an indispensable tool for myelin repair research. Several methods for isolation of rat OPCs from the CNS have been described, such as immunopanning 5,9,10 , fluorescence-activated cell sorting (FACS) by exploiting cell surface-specific antigens 5,11 , differential gradient centrifugation 7,8,12 or a shaking method based on differential adherent properties of glia 13,14 , which permits the separation of rat OPCs from the astroglial cells in the mixed glial culture by shearing forces.…”

Section: Introductionmentioning

confidence: 99%

Isolation and culture of rat and mouse oligodendrocyte precursor cells

et al. 2007

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“…O4 + oligodendrocytic cells were used in survival assays since cells of this stage of the oligodendrocyte lineage have the ability to divide and may be involved in the remyelination of axons in the CNS following brain injury (Gard and Pfeiffer 1993;Amat et al 1998;Keirstead and Blakemore 1999). Flow cytometry-purified O4 + pro-oligodendrocytes were diluted in DMEM and single cells were dispensed in a volume of 5 μl into wells of microwell plates (10-μl well capacity, 60 wells/plate; Nunc, Rochester, NY, USA.).…”

Section: Cell Survival Assaysmentioning

confidence: 99%

Recombinant EPF/chaperonin 10 promotes the survival of O4-positive pro-oligodendrocytes prepared from neonatal rat brain

McCombe

2008

Cell Stress and Chaperones

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Glial Cell Mitogens bFGF and PDGF Differentially Regulate Development of O4+GalC- Oligodendrocyte Progenitors

Cited by 167 publications

References 0 publications

cFLIP is critical for oligodendrocyte protection from inflammation

cFLIP is critical for oligodendrocyte protection from inflammation

Isolation and culture of rat and mouse oligodendrocyte precursor cells

Recombinant EPF/chaperonin 10 promotes the survival of O4-positive pro-oligodendrocytes prepared from neonatal rat brain

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