Endothelial cells of the blood-brain barrier: a target for glucocorticoids and estrogens?
Adhesion molecules are involved in the leukocyte recruitment of leukocytes at the blood-brain barrier. For this reason, it is important to understand how the regulation of their gene expression controls lymphocyte adhesion to endothelial cells in microvessels. Indeed, due to their specificity and diversity, adhesion molecules involved in extravasation play an essential role in the recruitment of activated leukocytes and activation of inflammation. Multiple sclerosis results from a chronic inflammation of the CNS which is mediated by infiltration of inflammatory cells from the immune system. Administration of glucocorticoids is a routine method to control multiple sclerosis since naturally derived or synthetic glucocorticoids are potent immunosuppressive and anti-inflammatory agents. Glucocorticoids also have beneficial effects in stabilizing the blood-brain barrier, as steroid hormones regulate the expression of adhesion molecule genes in endothelial cells. Other hormones such as estrogens modulate many endothelial cell biological activities, among them adhesion to leukocytes. They regulate expression of adhesion molecules genes on endothelial cells and are useful for the treatment of experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. The effects of glucocorticoids and estrogens on the expression of adhesion molecules on endothelial cells, including microvascular endothelial cells of the blood-brain barrier, are reviewed in this paper, as well as the involvement of these hormones in the therapy of experimental autoimmune encephalomyelitis and multiple sclerosis.
Dietrich
Jean-Bernard
JB
U 575 Inserm, 5, rue B. Pascal, 67084 Strasbourg, France. jbdietrich@neurochem.u-strasbg.fr
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy
D004967:Estrogens; D005938:Glucocorticoids