Abstract
Interferon-gamma (IFN-γ) is a pleiotropic inflammatory cytokine produced by T cells and natural killer cells. It is critically involved in the pathogenesis of the human demyelinating disease multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE). These diseases are mediated by activated self-reactive T cells, which target the central nervous system (CNS) oligodendrocytes and their myelin sheaths. In addition to its immunoregulatory properties, IFN-γ exerts a direct biological effect on CNS cells, providing, thereby, a link between CNS inflammation and cell injury. In this review, we discuss the role of IFN-γ in MS and EAE, as well as its involvement in the processes of oligodendrocyte injury and inflammatory demyelination. We summarize the molecular mechanisms of IFN-γ-induced oligodendrocyte injury and analyze the various experimental models that have been used for their elucidation. Finally, we discuss the disease-promoting role of IFN-γ's IRF-1/Caspase 1 signaling in MS and EAE, and draw attention to the potential therapeutic significance of its suppression. In conclusion, studying IFN-γ - oligodendrocyte interactions is likely to provide new perspective on the pathogenesis of MS.
Original language | English (US) |
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Title of host publication | Interferons |
Subtitle of host publication | Characterization, Mechanism of Action and Clinical Applications |
Publisher | Nova Science Publishers, Inc. |
Pages | 67-82 |
Number of pages | 16 |
ISBN (Print) | 9781620812983 |
State | Published - Sep 1 2012 |
Keywords
- Caspase 1
- Cell signaling
- Demyelination
- Experimental autoimmune encephalomyelitis
- IRF-1
- Inflammation
- Interferon-gamma
- Multiple sclerosis
- Oligodendrocytes
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology