The Effects of Estrogen on Theiler’s Virus Infection of Endothelial Cells
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Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The pathogenesis of this disease is not fully understood, but it is thought to be triggered by viral infection during early adulthood and is followed by autoimmune-mediated demyelination. Sex hormones are involved in the pathogenesis of MS since during pregnancy, women with MS undergo remission of the disease. Our laboratory uses Theiler’s virus-induced demyelination (TVID) as the animal model for studying MS. Theiler’s virus is a naturally occurring pathogen of mice, which causes an autoimmune-mediated demyelination of the central nervous system resulting in inflammatory lesions with similarities to human MS. In the current study we examined the effects of estrogen on Theiler’s virus infection of cells that form the blood-brain barrier (BBB): cerebral vascular endothelial (CVE) cells in vitro. The hypotheses to be tested were that (1) estrogen would have a protective effect on the CVE cells and that (2) estrogen treatment would alter the expression of microRNAs. Cloned CVE cells from BALB/c and C57Bl/6 mice were used in these experiments, which remain diploid and retain their differentiation markers for at least 20 passages in culture. In order to determine the effect of estrogen on modulating microRNAs within CVE, RNA was isolated from the cells and incorporated into miRNA chip analysis. We found miRNAs that are highly expressed in CVE: Let-7a, mmu miR-21, mmu miR-25, mmu miR-341, mmu miR-423, mmu miR-690. Cells were pre-treated with either 17β-estradiol, or ER-α agosnist propyl pyrazole triol (PPT) or ER-β agonist diarylpropionitrile (DPN). CVE cells were infected with TMEV at MOI of 10.0 for 24, 48, and 72h. Subsequently, the supernatants were used to measure cytotoxicity by LDH release assay. The results demonstrate that estrogen has a protective effect on CVE cells infected with TMEV and may therefore aid in the maintenance of the BBB integrity during viral infection. These results suggest that estrogen may have beneficial effects in a virus model of MS and may also be relevant for MS therapy.
Maher, Steven M. (2011). The Effects of Estrogen on Theiler’s Virus Infection of Endothelial Cells. Available electronically from