Flavonoids influence monocytic GTPase activity and are protective in experimental allergic encephalitis

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, whi...

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Bibliographic Details
Published in:The Journal of experimental medicine 2004-12, Vol.200 (12), p.1667-1672
Main Authors: Hendriks, Jerome J A, Alblas, Jacqueline, van der Pol, Susanne M A, van Tol, Eric A F, Dijkstra, Christine D, de Vries, Helga E
Format: Article
Language:English
Subjects:
Animals
Axons - metabolism
Axons - pathology
Blood-Brain Barrier - metabolism
Blood-Brain Barrier - pathology
Brief Definitive Report
Cell Movement - drug effects
Encephalomyelitis, Autoimmune, Experimental - drug therapy
Encephalomyelitis, Autoimmune, Experimental - metabolism
Encephalomyelitis, Autoimmune, Experimental - pathology
Endothelium, Vascular - metabolism
Endothelium, Vascular - pathology
Guinea Pigs
Luteolin - administration & dosage
Monocytes - metabolism
Monocytes - pathology
Multiple Sclerosis - metabolism
Multiple Sclerosis - pathology
Myelin Sheath - metabolism
Myelin Sheath - pathology
Rats
Rats, Inbred Lew
Reactive Oxygen Species - metabolism
rho GTP-Binding Proteins - metabolism
Signal Transduction - drug effects
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Summary: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.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20040819