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• W2140659630 endingPage "2971" @default.
• W2140659630 startingPage "2964" @default.
• W2140659630 abstract "Chemokines are small chemotactic cytokines that modulate leukocyte recruitment and activation during inflammation. Here, we describe the role of macrophage inflammatory protein-1alpha (MIP-1alpha) during cuprizone intoxication, a model where demyelination of the CNS features a large accumulation of microglia/macrophage without T cell involvement or blood-brain barrier disruption. RNase protection assays showed that mRNA for numerous chemokines were up-regulated during cuprizone treatment in wild-type, C57BL/6 mice. RANTES, inflammatory protein-10, and monocyte chemoattractant protein-1 showed greatest expression with initiation of insult at 1-2 wk of treatment, whereas MIP-1alpha and beta increased later at 4-5 wk, coincident with peak demyelination and cellular accumulation. The function of MIP-1alpha during demyelination was tested in vivo by exposing MIP-1alpha knockout mice (MIP-1alpha(-/-)) to cuprizone and comparing pathology to wild-type mice. Demyelination at 3.5 wk of treatment was significantly decreased in MIP-1alpha(-/-) mice ( approximately 36% reduction), a result confirmed by morphology at the electron microscopic level. The delay in demyelination was correlated to apparent decreases in microglia/macrophage and astrocyte accumulation and in TNF-alpha protein levels. It was possible that larger effects of the MIP-1alpha deficiency were being masked by other redundant chemokines. Indeed, RNase protection assays revealed increased expression of several chemokine transcripts in both untreated and cuprizone-treated MIP-1alpha(-/-) mice. Nonetheless, despite this possible compensation, our studies show the importance of MIP-1alpha in demyelination in the CNS and highlight its effect, particularly on cellular recruitment and cytokine regulation." @default.
• W2140659630 created "2016-06-24" @default.
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• W2140659630 date "2001-09-01" @default.
• W2140659630 modified "2023-10-16" @default.
• W2140659630 title "Absence of Macrophage-Inflammatory Protein-1α Delays Central Nervous System Demyelination in the Presence of an Intact Blood-Brain Barrier" @default.
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• W2140659630 doi "https://doi.org/10.4049/jimmunol.167.5.2964" @default.
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