Angiotensin II Type 1 receptor (AT1) signaling in astrocytes regulates synaptic degeneration-induced leukocyte entry to the central nervous system.

摘要: Abstract Astrocytes are the major cellular component of blood–brain barrier glia limitans and act as regulators leukocyte infiltration via chemokine expression. We have studied angiotensin-II receptor Type 1 (AT1) related NF-κB signaling in astrocytes. Angiotensin II derives from cleavage angiotensin I by converting enzyme (ACE), deriving angiotensinogen renin. Level expression ACE was slightly increased transgenic mice that express dominant-negative IκBα astrocytes (GFAP-IκBα-dn mice), whereas renin, also constitutively expressed CNS, were unaffected inhibition. Leukocytes infiltrate hippocampus after unilateral stereotactic lesion afferent perforant path axons entorhinal cortex. Upregulation CXCL10 normally occurs response to synaptic degeneration dentate gyrus following axonal transection totally abrogated GFAP-IκBα-dn mice. Whereas upregulated microglia post-lesion, AT1 exclusively on Blocking with Candesartan led significant increase numbers infiltrating macrophages 2 days post-lesion. Lesion-induced increases T-cell morphologic glial unaffected, blood-brain remained intact horseradish peroxidase. These findings show plays an important role regulation CNS a neurodegenerative stimulus, identify potential targets for therapies directed at adaptive immune responses CNS.