Proteomic analysis of human cerebral endothelial cells activated by multiple sclerosis serum and IFNbeta-1b

Abstract

Several groups have recently described the endothelial cell (EC) as an important target of pathological mediators in multiple sclerosis (MS). Despite the recognition of the EC as a significant target in MS and a possible beneficiary of Beta-interferon therapy, the structural changes which occur in the cerebrovascular endothelium and the effects of interferon-beta 1b on these changes have not been closely evaluated. Disruption or dysregulation of the blood brain barrier (BBB) in MS represents a loss of endothelial integrity, which may facilitate the transendothelial migration of activated leukocytes responsible for the development of demyelinating lesions of MS. We used proteomics (2-dimensional gel electrophoresis and MALDI-MS) to characterize the effects of serum from MS patients with active disease (with and without interferon-beta 1b therapy) on human cerebral endothelial cells. The results of this study revealed the up- and down-regulation of expression of several proteins related to blood vessel development, cell structure, and cell cycle control. Using this approach we have identified protein 14-3-3, metavinculin, myosin-9, plasminogen, reticulocalbin-2 and-3, ribonuclease/angiogenin inhibitor 1, annexin A1, tropomyosin and Ras-related protein Rap-1A as potential new markers of active MS disease. A more complete description of cerebrovascular endothelial biomarkers and mediators in MS pathogenesis and how they are regulated by inflammatory cytokines and beta-interferons may lead to the development of more effective therapies and more accurate diagnostic markers in MS.