Increase in chemokine CXCL1 by ER? ligand treatment is a key mediator in promoting axon myelination.

ABSTRACT: Estrogen receptor ? (ER?) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ER? ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ER? ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ER? ligands at peak EAE were assessed. All ER? ligands induced differential expression of cytokines and chemokines, but increased levels of CXCL1 in the periphery and in astrocytes. Oligodendrocyte CXCR2 binds CXCL1 and has been implicated in normal myelination. In addition, despite extensive immune cell accumulation in the CNS, all ER? ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ER? ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ER? ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis.

SUBMITTER: Karim H 

PROVIDER: S-EPMC6004485 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature