Published 20 December 2004. doi:10.1084/jem.20040819
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 12, 1667-1672
Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis
Jerome J.A. Hendriks1,
Jacqueline Alblas1,
Susanne M.A. van der Pol1,
Eric A.F. van Tol2,
Christine D. Dijkstra1, and
Helga E. de Vries1
1 Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center (VUMC), 1007 MB Amsterdam, Netherlands
2 Biomedical Research Department, Numico Research B.V., 6704 PH Wageningen, Netherlands
Address correspondence to Helga E. de Vries, Dept. of Molecular Cell Biology and Immunology, VUMC, FdG, PO Box 7057, 1007 MB Amsterdam, Netherlands. Phone: 31-20-444-8077; Fax: 31-20-444-8081; email: he.devries{at}vumc.nl
In the chronic disabling disease multiple sclerosis (MS), migration of monocytes across the blood-brain barrier is a crucial step in the formation of new lesions in the central nervous system (CNS). Infiltrating monocyte-derived macrophages secrete inflammatory mediators such as oxygen radicals, which contribute to axonal demyelination and damage, resulting in neurological deficits. Flavonoids are compounds occurring naturally in food, which scavenge oxygen radicals and have antiinflammatory properties. To investigate whether they might suppress clinical symptoms in MS, we treated rats sensitized for acute and chronic experimental allergic encephalomyelitis, an experimental model of MS, with flavonoids. We demonstrated that the flavonoid luteolin substantially suppressed clinical symptoms and prevented relapse when administered either before or after disease onset. Luteolin treatment resulted in reduced inflammation and axonal damage in the CNS by preventing monocyte migration across the brain endothelium. Luteolin influenced migration by modulating the activity of Rho GTPases, signal transducers involved in transendothelial migration. Oral administration of luteolin also significantly reduced clinical symptoms.
Key Words: multiple sclerosis • luteolin • blood-brain barrier • macrophage • RhoA
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