Extra-cellular Matrix protein 1 (ECM1) Ameliorates Experimental Autoimmune Encephalomyelitis (EAE) through Inhibition of MMP9 Activity

Abstract

Abstract Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE), an animal model representing human multiple sclerosis (MS), is mainly mediated by Th1 and Th17 cells. Matrix metalloproteinase-9 (MMP9), a zinc bound protease, plays an important role in the invasion or infiltration of pathogenic Th cells into CNS during MS/EAE. In current study, we find that ECM1 could inhibit MMP9 activity through protein/protein interaction in vitro and ameliorate MOG-induced EAE via blocking MMP9-mediated invasion/infiltration of pathogenic Th cells into CNS in vivo. Giving ECM1 protein treatment on the late periods of pathogenic T cell migration in EAE model, the EAE disease is significantly attenuated. This treatment functions by reduction of infiltrating pathogenic Th cells into CNS, but had no impact on Th1/Th17 cell development in the peripheral lymphoid tissues. Our results suggest that ECM1 is potential an inhibitor to treat EAE disease.