Effect of the Sera of Patients with Multiple Sclerosis on Apoptosis and Nitric Oxide Production of Endothelial Cells

Authors

1 Associate Professor, Physiology Dep., School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Master of Physiology, Physiology Research Center, Isfahan University of Medical Sciences, Isfahan

3 Associate Professor, Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Student of Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

5 Master of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran

6 Professor, Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

Abstract

Background & Aims: Multiple sclerosis (MS) is one of the chronic autoimmune diseases of the central nervous system with unknown etiology. The present study aimed to investigate the apoptosis and nitric oxide (NO) production of endothelial cells treated with serum of patients with MS and response to interferon beta (IFN- ) therapy. Methods: 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 = 10). Nitric oxide (NO) levels were determined in culture supernatants by Greiss method and endothelial cell apoptosis was assessed by annexin V-propidium iodide staining. Effects of IFN-beta-1b on endothelial cell apoptosis and NO production were tested at increasing doses (10, 100, and 1000 U/ml). Results: Compared with healthy people, only apoptosis of endothelial cells treated with serum of patients with relapsing phase increased, P<0.01; while there was no significant difference between apoptosis of endothelial cells treated with serum of patients in remission phase and healthy controls. Apoptosis of endothelial cells treated with sera of patients in relapse was decreased by IFN-beta-1b at 10 U/ml, P<0.05. The same dose also led to a significant increase in nitric oxide production. Conclusion: The results suggest that endothelial cells injury and apoptosis may play a role in MS etiology and represents a potential therapeutic mechanism of action for IFN-beta-1b in MS therapy.

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