Blockade of the kinin receptor B1 protects from XXXX by reducing leukocyte trafficking.

@entity6504 @entity32 @entity1 @entity15347 @entity3026 @entity19 @entity164 @entity1812 @entity6503 @entity29138 @entity15
Disruption of the blood brain barrier (BBB) and transendothelial trafficking of immune cells into the central nervous system (CNS) are pathophysiological hallmarks of @entity15 ( @entity15 ) and its animal model, @entity6503 ( @entity6503 ). Kinins are proinflammatory peptides which are released during tissue injury including @entity6503 . They increase vascular permeability and enhance @entity32 by acting on distinct @entity1812 receptors, @entity29138 and @entity15347 . We studied the expression of @entity29138 and @entity15347 and the effect of their inhibition on the disease course, BBB integrity and T cell migration following @entity6504 ( @entity6504 (35-55))-induced @entity6503 . @entity29138 , but not @entity15347 expression was markedly enhanced in inflammatory CNS lesions in @entity19 and @entity1 . Brain endothelial cells could be identified as major source of @entity29138 protein. The severity of @entity6503 was significantly alleviated in @entity29138 (-/-) @entity19 compared with @entity164 ( @entity164 ) controls (P<0.05). Treatment of @entity164 @entity19 with the @entity29138 antagonist R715 before and after disease onset was equally effective (P<0.05) while @entity29138 activation by R838 promoted @entity6503 (P<0.05). @entity29138 inhibition was accompanied by a remarkable reduction of BBB disruption and tissue @entity32 . In vitro analyses revealed that @entity29138 suppression reverses the upregulation of ICAM-I and VCAM-I at the inflamed BBB thereby limiting T cell transmigration. In contrast, blocking @entity15347 had no significant impact on @entity6503 . We conclude that @entity29138 inhibition can reduce BBB damage and cell invasion during @entity3026 and may offer a novel anti-inflammatory strategy for the treatment of @entity15 .
