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Multiple Sclerosis
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Serum from patients with multiple sclerosis downregulates occludin and VE-cadherin expression in cultured endothelial cells

Alireza Minagar

Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130-3932, USA

Dmitry Ostanin

Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130-3932, USA

Ann C Long

Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130-3932, USA

Merilyn Jennings

Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130-3932, USA

Roger E Kelley

Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130-3932, USA

Makoto Sasaki

Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130-3932, USA

J Steven Alexander

Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130-3932, USA, jalexa{at}lsuhsc.edu

Disruption of the blood -brain barrier (BBB) and transendothelial migration of inflammatory cells are crucial steps in the development of demyelinating lesions in multiple sclerosis (MS). O ccludin and vascular endothelial-cadher in (VE-cadherin) are two major components of the tight junctions (TJs) in the brain microvasculature that help to create the BBB. In the present study, we investigated the effect of serum from MS patients on the expression of these two junctional markers and on the endothelial integrity. Serum from six MS patients in exacerbation, six in remission, and six normal controls (10% by volume) was incubated with cultured endothelial cells, and the expression of occludin and VE-cadherin was measured by immunoblotting. Serum from MS patients in exacerbation significantly reduced the expression of occludin and VE-cadherin compared with patients in remission and normal controls. This disintegrating effect was more pronounced for occludin than for VE-cadherin. We assume that the elevation in cytokines or other serum-soluble factors in MS patients in exacerbation likely provokes downregulation of occludin and VE-cadherin. This downregulation of TJs proteins may, therefore, contribute to the disruption of the BBB in this condition.

Key Words: blood-brain barrier • endothelial cells • multiple sclerosis • occludin • transendothelial migration • VE-cadherin

Multiple Sclerosis, Vol. 9, No. 3, 235-238 (2003)
DOI: 10.1191/1352458503ms916oa


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