Serum from patients with multiple sclerosis downregulates occludin and VE-cadherin expression in cultured endothelial cells.
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). Occludin and vascular endothelial-cadherin (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.
Minagar
Alireza
A
Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Ostanin
Dmitry
D
Long
Ann C
AC
Jennings
Merilyn
M
Kelley
Roger E
RE
Sasaki
Makoto
M
Alexander
J Steven
JS
D000328:Adult; D015703:Antigens, CD; D001790:Blood Physiological Phenomena; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002199:Capillary Permeability; D016022:Case-Control Studies; D002460:Cell Line; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000503:physiopathology; D062793:Occludin; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D008565:Membrane Proteins; D062793:Occludin; D000099152:Cadherin 5; C568985:OCLN protein, human