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

Estrogen receptor ß (ERß) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ERß ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ERß ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ERß ligands at peak EAE were assessed. All ERß 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 ERß ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ERß ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ERß ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis.