PMID- 12458035
OWN - NLM
STAT- MEDLINE
DCOM- 20021209
LR  - 20190826
IS  - 0165-5728 (Print)
IS  - 0165-5728 (Linking)
VI  - 131
IP  - 1-2
DP  - 2002 Oct
TI  - Substance P antagonist blocks leakage and reduces activation of 
      cytokine-stimulated rat brain endothelium.
PG  - 41-9
AB  - 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.
FAU - Annunziata, Pasquale
AU  - Annunziata P
AD  - Institute of Neurological Sciences, University of Siena, Viale Bracci, 2, 53100, 
      Siena, Italy. annunziata@unisi.it
FAU - Cioni, Chiara
AU  - Cioni C
FAU - Santonini, Riccardo
AU  - Santonini R
FAU - Paccagnini, Eugenio
AU  - Paccagnini E
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Albumins)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 33507-63-0 (Substance P)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 91224-37-2 (spantide)
SB  - IM
MH  - Albumins/metabolism
MH  - Animals
MH  - *Blood-Brain Barrier/drug effects
MH  - Brain/blood supply/cytology/*metabolism
MH  - Cells, Cultured
MH  - Cytokines/*antagonists & inhibitors
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/drug effects/*metabolism/ultrastructure
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interferon-gamma/antagonists & inhibitors
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substance P/*analogs & derivatives/*antagonists & 
      inhibitors/biosynthesis/genetics/*pharmacology
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors
EDAT- 2002/11/30 04:00
MHDA- 2002/12/10 04:00
CRDT- 2002/11/30 04:00
PHST- 2002/11/30 04:00 [pubmed]
PHST- 2002/12/10 04:00 [medline]
PHST- 2002/11/30 04:00 [entrez]
AID - S016557280200262X [pii]
AID - 10.1016/s0165-5728(02)00262-x [doi]
PST - ppublish
SO  - J Neuroimmunol. 2002 Oct;131(1-2):41-9. doi: 10.1016/s0165-5728(02)00262-x.