The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence.
Science
; 334(6063): 1727-31, 2011 Dec 23.
Article
em En
| MEDLINE
| ID: mdl-22144466
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Barreira Hematoencefálica
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Transdução de Sinais
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Astrócitos
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Células Endoteliais
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Proteínas Hedgehog
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2011
Tipo de documento:
Article