We recently demonstrated that substance P mediates increased permeability of brain endothelium exposed to HIV-1 gp120. To test whether substance P is involved in immune processes at the blood-brain barrier (BBB), we stimulated rat brain endothelial cultures prepared from cerebral microvessels with Interferon-gamma (IFN-gamma) and Tumor necrosis factor-alpha (TNF-alpha), two proinflammatory cytokines that alter the BBB and measured permeability to albumin and expression of adhesion molecule ICAM-1 and MHC class II antigen in the presence and absence of spantide, a powerful substance P antagonist. In a dose-dependent manner, spantide completely neutralized increased permeability induced by TNF-alpha and IFN-gamma and expression of MHC class II molecule induced by IFN-gamma and prevented associated cell morphological changes as revealed by scanning electron microscope. Spantide also reduced expression of ICAM-1 induced by TNF-alpha and IFN-gamma by 35% and 30%, respectively. Substance P mRNA was found in unstimulated brain endothelial cells and was upregulated after stimulation with TNF-alpha and IFN-gamma. These in vitro findings demonstrate that substance P plays a major pathogenetic role in damaging and activating the BBB vascular component in the presence of proinflammatory cytokines.
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|Titolo:||Substance P antagonist blocks leakage and reduces activation of cytokine-stimulated rat brain endothelium.|
|Rivista:||JOURNAL OF NEUROIMMUNOLOGY|
|Citazione:||Annunziata, P., Cioni, C., Santonini, R., & Paccagnini, E. (2002). Substance P antagonist blocks leakage and reduces activation of cytokine-stimulated rat brain endothelium. JOURNAL OF NEUROIMMUNOLOGY, 131, 41-49.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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