[Frontiers in Bioscience E4, 1368-1374, January 1, 2012]

Interferon-beta-1b protects against multiple sclerosis-induced endothelial cells apoptosis

Shaghayegh Haghjooy Javanmard 1, Mohammad Saadatnia M2,3 , Vida Homayouni V1, Mahin Nikoogoftar M4, Amir H. Maghzi3,5, Etemadifar M3, Chaitanya VG6, Jeanie C. McGee7, Alireza Minagar7, J. Steven Alexander6

1Applied Physiology Research Center, Department of Physiology, Isfahan University of Medical Sciences, Hezar Jerib Avenue, Isfahan, Iran, 2Isfahan Medical Education Research Center, Isfahan University of Medical Sciences, Isfahan, Iran, 3Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran, 4Department of Hematology, School of Medicine, Tarbiat Modarres University, Tehran, Iran, 5Neuroimmunology unit, Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School  of Medicine and Dentistry, London,  UK Departments of Molecular and Cellular Physiology6 and Neurology7, Shreveport, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Methods
3.1. Patients and control subjects
3.2. Cell culture
3.3. Apoptosis analysis
3.4. Nitric oxide (NO) metabolite (Nitrite, NO2-) measurement
3.5. Statistical analysis
4. Results
5. Discussion
5.1. Endothelial dysfunction in MS
5.2. IFN-beta-1b and apoptosis
5.3. Dose-dependent effects of IFN-beta-1b
5.4. Correlation of nitric oxide production with reduction in apoptosis
6. Acknowledgements
7. References

1. ABSTRACT

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.