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.

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(1-2), 41-49 [10.1016/S0165-5728(02)00262-X].

Substance P antagonist blocks leakage and reduces activation of cytokine-stimulated rat brain endothelium

ANNUNZIATA P.;CIONI C.;PACCAGNINI E.
2002-01-01

Abstract

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.
2002
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(1-2), 41-49 [10.1016/S0165-5728(02)00262-X].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/30220
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