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| - Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5(−/−)) mice. CCR5(−/−) and CCR5(+/+) (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5(−/−) mice than CCR5(+/+) mice. Immune cells (CD3(+), CD4(+), CD8(+), B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5(−/−) mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5(−/−) mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5(−/−) mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.
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