TY - JOUR
T1 - Interferon-beta-1beta protects against multiple sclerosis-induced endothelial cells apoptosis
AU - Javanmard, Shaghayegh Haghjooy
AU - Mohammad Saadatnia, M.
AU - Vida Homayouni, V.
AU - Mahin Nikoogoftar, M.
AU - Maghzi, Amir H.
AU - Etemadifar, M.
AU - Chaitanya, V. G.
AU - McGee, Jeanie C.
AU - Minagar, Alireza
AU - Alexander, J. Steven
PY - 2012/1/1
Y1 - 2012/1/1
N2 - Disruption of the blood-brain-barrier (BBB) due to endothelial cell (EC) injury is an essential step in formation of multiple sclerosis (MS) lesions. We investigated the role of endothelial cell (EC) apoptosis in the pathophysiology of MS, studying the therapeutic effect of IFN-beta-1b against MS sera-induced endothelial apoptosis. Human umbilical vein endothelial cells were treated with sera from patients with active MS (in relapse), MS in remission, or sera from healthy volunteers (each n = 5). Apoptosis was assessed by annexin V-propidium iodide staining. Effects of IFN-beta-1b on EC apoptosis were tested at increasing doses (10, 100, and1000 U/ml). Nitrite (NO2--) levels were determined in culture supernatants. EC apoptosis was increased by sera from exacerbating MS patients, but not remission, compared to healthy individuals (p<0.001). Effects were blocked by IFN-beta-1b at 10U/ml (p<0.05), but not higher doses, and was associated with increased NO/NO2- production (p<0.05). EC apoptosis leading to disruption of the BBB may play a role in MS etiology and represents a novel therapeutic mechanism of action for IFN-beta-1b in MS therapy.
AB - Disruption of the blood-brain-barrier (BBB) due to endothelial cell (EC) injury is an essential step in formation of multiple sclerosis (MS) lesions. We investigated the role of endothelial cell (EC) apoptosis in the pathophysiology of MS, studying the therapeutic effect of IFN-beta-1b against MS sera-induced endothelial apoptosis. Human umbilical vein endothelial cells were treated with sera from patients with active MS (in relapse), MS in remission, or sera from healthy volunteers (each n = 5). Apoptosis was assessed by annexin V-propidium iodide staining. Effects of IFN-beta-1b on EC apoptosis were tested at increasing doses (10, 100, and1000 U/ml). Nitrite (NO2--) levels were determined in culture supernatants. EC apoptosis was increased by sera from exacerbating MS patients, but not remission, compared to healthy individuals (p<0.001). Effects were blocked by IFN-beta-1b at 10U/ml (p<0.05), but not higher doses, and was associated with increased NO/NO2- production (p<0.05). EC apoptosis leading to disruption of the BBB may play a role in MS etiology and represents a novel therapeutic mechanism of action for IFN-beta-1b in MS therapy.
KW - Apoptosis
KW - Endothelial Cell
KW - Interferon-Beta
KW - Multiple sclerosis
KW - Nitric Oxide
UR - http://www.scopus.com/inward/record.url?scp=84860876682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860876682&partnerID=8YFLogxK
M3 - Article
C2 - 22201961
AN - SCOPUS:84860876682
VL - 4 E
SP - 1368
EP - 1374
JO - Frontiers in Bioscience - Elite
JF - Frontiers in Bioscience - Elite
SN - 1945-0494
IS - 4
ER -