Investigation of the Effects of Glucocortiocid Treatment on the CNS Proteome During EAE in the Absence of MIF

Date
2018
Authors
Escobar, Daniel Alberto
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Abstract

Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease characterized by damage to the myelin sheath surrounding neuronal axons. As there is currently no cure for multiple sclerosis, treatment methods aim to mediate the symptoms of the disease. The most common type of treatment for acute exacerbations of multiple sclerosis is glucocorticoid (GC) drugs. It is known that GC's induce the expression of the inflammatory cytokine macrophage migration inhibitory factor (MIF). The expression of this inflammatory cytokine reduces the efficacy of GC treatment. Previous work in our lab has shown that knock-out of MIF in conjunction with dexamethasone (Dex) treatment attenuates disease significantly more than Dex treatment in MIF sufficient mice. Our goal was to compare brain proteomes between MIF KO and WT EAE mice to better understand the mechanisms that underlie how MIF inhibition enhances the efficacy of GC treatment to attenuate disease. Using a high-throughput liquid chromatography mass spectrometry technique, several proteins were identified that exhibited differential protein expression between the MIF KO and WT mice at both 48 hours and 10 days post initiation of Dex treatment. We hypothesize that proteins expressed differentially between MIF KO mice and WT mice treated with Dex could provide novel therapeutic targets for the treatment of inflammatory autoimmune diseases.

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Integrative Biology