Publication Date:
2011-12-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alvarez, Jorge Ivan -- Dodelet-Devillers, Aurore -- Kebir, Hania -- Ifergan, Igal -- Fabre, Pierre J -- Terouz, Simone -- Sabbagh, Mike -- Wosik, Karolina -- Bourbonniere, Lyne -- Bernard, Monique -- van Horssen, Jack -- de Vries, Helga E -- Charron, Frederic -- Prat, Alexandre -- MOP74700/Canadian Institutes of Health Research/Canada -- MOP81880/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2011 Dec 23;334(6063):1727-31. doi: 10.1126/science.1206936. Epub 2011 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroimmunology Unit, Center of Excellence in Neuromics, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, Faculty of Medicine, Universite de Montreal, Montreal, Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22144466" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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