Cargando…
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...
Autores principales: | , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212002/ https://www.ncbi.nlm.nih.gov/pubmed/15611292 http://dx.doi.org/10.1084/jem.20040819 |
_version_ | 1782148601498042368 |
---|---|
author | Hendriks, Jerome J.A. Alblas, Jacqueline van der Pol, Susanne M.A. van Tol, Eric A.F. Dijkstra, Christine D. de Vries, Helga E. |
author_facet | Hendriks, Jerome J.A. Alblas, Jacqueline van der Pol, Susanne M.A. van Tol, Eric A.F. Dijkstra, Christine D. de Vries, Helga E. |
author_sort | Hendriks, Jerome J.A. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2212002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22120022008-03-11 Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis Hendriks, Jerome J.A. Alblas, Jacqueline van der Pol, Susanne M.A. van Tol, Eric A.F. Dijkstra, Christine D. de Vries, Helga E. J Exp Med Brief Definitive Report 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. The Rockefeller University Press 2004-12-20 /pmc/articles/PMC2212002/ /pubmed/15611292 http://dx.doi.org/10.1084/jem.20040819 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Hendriks, Jerome J.A. Alblas, Jacqueline van der Pol, Susanne M.A. van Tol, Eric A.F. Dijkstra, Christine D. de Vries, Helga E. Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis |
title | Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis |
title_full | Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis |
title_fullStr | Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis |
title_full_unstemmed | Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis |
title_short | Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis |
title_sort | flavonoids influence monocytic gtpase activity and are protective in experimental allergic encephalitis |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212002/ https://www.ncbi.nlm.nih.gov/pubmed/15611292 http://dx.doi.org/10.1084/jem.20040819 |
work_keys_str_mv | AT hendriksjeromeja flavonoidsinfluencemonocyticgtpaseactivityandareprotectiveinexperimentalallergicencephalitis AT alblasjacqueline flavonoidsinfluencemonocyticgtpaseactivityandareprotectiveinexperimentalallergicencephalitis AT vanderpolsusannema flavonoidsinfluencemonocyticgtpaseactivityandareprotectiveinexperimentalallergicencephalitis AT vantolericaf flavonoidsinfluencemonocyticgtpaseactivityandareprotectiveinexperimentalallergicencephalitis AT dijkstrachristined flavonoidsinfluencemonocyticgtpaseactivityandareprotectiveinexperimentalallergicencephalitis AT devrieshelgae flavonoidsinfluencemonocyticgtpaseactivityandareprotectiveinexperimentalallergicencephalitis |