| The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. | |
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MedLine Citation:
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PMID: 22144466 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The blood-brain barrier (BBB) is composed of tightly bound endothelial cells (ECs) and perivascular astrocytes that regulate central nervous system (CNS) homeostasis. We showed that astrocytes secrete Sonic hedgehog and that BBB ECs express Hedgehog (Hh) receptors, which together promote BBB formation and integrity during embryonic development and adulthood. Using pharmacological inhibition and genetic inactivation of the Hh signaling pathway in ECs, we also demonstrated a critical role of the Hh pathway in promoting the immune quiescence of BBB ECs by decreasing the expression of proinflammatory mediators and the adhesion and migration of leukocytes, in vivo and in vitro. Overall, the Hh pathway provides a barrier-promoting effect and an endogenous anti-inflammatory balance to CNS-directed immune attacks, as occurs in multiple sclerosis. |
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Authors:
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Jorge Ivan Alvarez; Aurore Dodelet-Devillers; Hania Kebir; Igal Ifergan; Pierre J Fabre; Simone Terouz; Mike Sabbagh; Karolina Wosik; Lyne Bourbonnière; Monique Bernard; Jack van Horssen; Helga E de Vries; Frédéric Charron; Alexandre Prat |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-12-01 |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 334 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-23 Completed Date: 2012-01-25 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1727-31 Citation Subset: IM |
Affiliation:
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Neuroimmunology Unit, Center of Excellence in Neuromics, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytes / metabolism* Blood-Brain Barrier / cytology, physiology* Brain / immunology*, physiology CD4-Positive T-Lymphocytes / physiology Cell Adhesion Cell Movement Cells, Cultured Chemokines / metabolism Electric Impedance Encephalomyelitis, Autoimmune, Experimental / immunology, metabolism Endothelial Cells / metabolism* Female Hedgehog Proteins / genetics, metabolism* Humans Inflammation Mediators / metabolism Mice Mice, Inbred C57BL Multiple Sclerosis / immunology, metabolism Permeability Signal Transduction* Veratrum Alkaloids / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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MOP74700//Canadian Institutes of Health Research; MOP81880//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Chemokines; 0/Hedgehog Proteins; 0/Inflammation Mediators; 0/SHH protein, human; 0/Shh protein, mouse; 0/Veratrum Alkaloids; 4449-51-8/cyclopamine |
| Comments/Corrections | |
Comment In:
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Science. 2011 Dec 23;334(6063):1652-3
[PMID:
22194564
]
Nat Rev Immunol. 2012 Jan;12(1):4 [PMID: 22193763 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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