ONCOSTATIN M IS A POTENT INDUCER OF CNS INFLAMMATION

Abstract

The neuropoietic cytokine oncostatin M (OSM) is expressed in MS lesions, but its function during CNS lesion development is unknown. We have induced local expression of OSM in the CNS of C57Bl/6J mice by means of lentiviral vectors. Our data demonstrate that at sites of OSM expression, tissue remodelling occurs and an irregular deposition of the basement membrane protein laminin is detected. Further analysis demonstrated that local OSM expression disrupts several aspects of the blood-brain barrier (BBB): large perivascular spaces were found between the inner and outer basement membranes, expression of the tight junction protein ZO-1 was altered and serum leaks into the CNS parenchyma. In addition, local OSM expression induced an upregulation of adhesion molecules on endothelial cells of the BBB. Moreover, OSM-expression was accompanied by an upregulation of MHCII molecules and an infiltration of T-cells and macrophages/microglia into the brain. This is the first study demonstrating that local OSM expression in the healthy CNS is sufficient to induce several aspects charateristic of neuroinflammation.