Laquinimod enhances central nervous system barrier functions.
Neurobiol Dis
; 102: 60-69, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28235673
ABSTRACT
Laquinimod is currently being tested as a therapeutic drug in multiple sclerosis. However, its exact mechanism of action is still under investigation. Tracking of fluorescently-tagged encephalitogenic T cells during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, revealed that laquinimod significantly reduces the invasion of pathogenic effector T cells into the CNS tissue. T-cell activation, differentiation and amplification within secondary lymphoid organs after immunization with myelin antigen, their migratory capacity and re-activation within the nervous tissue were either only mildly affected or remained unchanged. Instead, laquinimod directly impacted the functionality of the CNS vasculature. The expression of tight junction proteins p120 and ZO-1 in human brain endothelial cells was up-regulated upon laquinimod treatment, resulting in a significant increase in the transendothelial electrical resistance of confluent monolayers of brain endothelial cells. Similarly, expression of the adhesion molecule activated leukocyte cell adhesion molecule (ALCAM) and inflammatory chemokines CCL2 and IP-10 was suppressed, leading to a significant reduction in the migration of memory TH1 and TH17 lymphocytes across the blood brain barrier (BBB). Our data indicate that laquinimod exerts its therapeutic effects by tightening the BBB and limiting parenchymal invasion of effector T cells, thereby reducing CNS damage.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
/
Quinolonas
/
Fármacos Neuroprotetores
Limite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article