Production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1 in rat brain is stimulated by intracerebroventricular administration of an endothelin ETB receptor agonist

Abstract

The role of endothelin (ET)B receptors in chemokine production in the brain of rats was examined. Intracerebroventricular administration of 500 pmol/day of Ala(1,3,11,15)-ET-1, a selective ETB agonist, for 3 or 7 days increased monocyte chemoattractant protein (MCP)-1 and cytokine-induced neutrophil chemoattractant (CINC)-1 mRNA in the caudate-putamen and cerebrum, whereas it had no effects on regulated on activation normal T-cell expressed and secreted (RANTES), fractalkine and stromal cell-derived factor (SDF)-1alpha mRNA expression. Immunoreactive MCP-1 and CINC-1 in the caudate-putamen and the cerebrum were increased by the ETB agonist. Immunohistochemical observations on the Ala(1,3,11,15)-ET-1-infused rats showed that glial fibrillary acidic protein-positive astrocytes had immunoreactivity for MCP-1 and CINC-1. These findings indicate that the activation of brain ETB receptors causes the production of MCP-1 and CINC-1, and suggest a pathophysiological role for brain ETB receptors in nervous system damage.