Contributions
Abstract: P1905
Type: Poster
Abstract Category: Late breaking news
Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS), characterized by focal areas of inflammation in which myelin, oligodendrocytes (OLGs) and neurons are damaged. In healthy brain, leukocyte infiltration into the CNS is limited by the blood-brain barrier (BBB), consisting of tightly sealed and highly specialized endothelial cells (ECs) surrounded by a continuous basement membrane and astrocytic end feet. In MS however, this tightly regulated immune surveillance is hampered, leading to infiltration of myelin-specific T-cells into the CNS parenchyma. Oncostatin M (OSM), a member of the interleukin (IL)-6 cytokine family, is produced in lesions of MS patients and we demonstrated in previous research that OSM protects against demyelination in the cuprizone mouse model and enhances neurite outgrowth during spinal cord injury. High expression of the OSM receptor (OSMR) was found on brain microvascular endothelial cells (BMECs). Therefore, we hypothesize that OSM also has a protective role in CNS damage at the level of the BBB. In vitro experiments reveal a decrease (p< 0.01) in vascular cell adhesion protein 1 (VCAM-1) expression on BMECs after OSM (25 ng/ml) treatment under inflammatory conditions. The same trend is visible for intercellular adhesion molecule -1 (ICAM-1). For mRNA levels of tight (occludin, claudin5, ZO-1) and adhesion junctions (catenin alpha 1, VE-cadherin), no effect of OSM is detected, although the effect on the protein level and junction structure needs to be elucidated. To investigate the effect of OSM on the BBB in vivo, the experimental autoimmune encephalomyelitis (EAE) was induced in OSMR KO animals. Here, a reduced disease score (p=0.0351, F(1,42)=4.743) is present in OSMR KO mice. The in vitro data imply a protective effect of OSM on the BBB, while the in vivo data suggest the opposite. Additional in vitro experiments including permeability assays and immunohistochemistry for tight and adhesion junctions, next to tissue analysis of the EAE pilot will help reveal the true role of OSM on the BBB in MS.
Disclosure:
E. Houben: nothing to disclose
B. Broux: nothing to disclose
K. Janssens: nothing to disclose
H. Slaets: nothing to disclose
N. Hellings: nothing to disclose
Abstract: P1905
Type: Poster
Abstract Category: Late breaking news
Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS), characterized by focal areas of inflammation in which myelin, oligodendrocytes (OLGs) and neurons are damaged. In healthy brain, leukocyte infiltration into the CNS is limited by the blood-brain barrier (BBB), consisting of tightly sealed and highly specialized endothelial cells (ECs) surrounded by a continuous basement membrane and astrocytic end feet. In MS however, this tightly regulated immune surveillance is hampered, leading to infiltration of myelin-specific T-cells into the CNS parenchyma. Oncostatin M (OSM), a member of the interleukin (IL)-6 cytokine family, is produced in lesions of MS patients and we demonstrated in previous research that OSM protects against demyelination in the cuprizone mouse model and enhances neurite outgrowth during spinal cord injury. High expression of the OSM receptor (OSMR) was found on brain microvascular endothelial cells (BMECs). Therefore, we hypothesize that OSM also has a protective role in CNS damage at the level of the BBB. In vitro experiments reveal a decrease (p< 0.01) in vascular cell adhesion protein 1 (VCAM-1) expression on BMECs after OSM (25 ng/ml) treatment under inflammatory conditions. The same trend is visible for intercellular adhesion molecule -1 (ICAM-1). For mRNA levels of tight (occludin, claudin5, ZO-1) and adhesion junctions (catenin alpha 1, VE-cadherin), no effect of OSM is detected, although the effect on the protein level and junction structure needs to be elucidated. To investigate the effect of OSM on the BBB in vivo, the experimental autoimmune encephalomyelitis (EAE) was induced in OSMR KO animals. Here, a reduced disease score (p=0.0351, F(1,42)=4.743) is present in OSMR KO mice. The in vitro data imply a protective effect of OSM on the BBB, while the in vivo data suggest the opposite. Additional in vitro experiments including permeability assays and immunohistochemistry for tight and adhesion junctions, next to tissue analysis of the EAE pilot will help reveal the true role of OSM on the BBB in MS.
Disclosure:
E. Houben: nothing to disclose
B. Broux: nothing to disclose
K. Janssens: nothing to disclose
H. Slaets: nothing to disclose
N. Hellings: nothing to disclose