Abstract |
We have studied the effect of interferon (IF) beta-1a on the basal and TNFalpha-induced intercellular adhesion molecule 1 (ICAM 1) expression and fluid phase endocytosis (FPE) of horseradish peroxidase in cultured rat brain microvascular endothelial cells. Neither basal ICAM 1 expression nor basal FPE were significantly affected by 24-72 h exposure to 1000 U/ml IFbeta-1a. ICAM 1 induction and FPE enhancement caused by 100 U/ml TNFalpha for 24 h was not influenced by simultaneous administration of 1000 U/ml IFbeta-1a. Treatment of cultures with IFbeta-1a for 48 h followed by 24-h coincubation with TNFalpha (100 U/ml) and IFbeta-1a (1000 U/ml) resulted in significant downregulation of TNFalpha-induced ICAM 1 expression and FPE. Downregulation of TNFalpha-induced ICAM 1 expression was not observed when combined treatment with TNFalpha (100 U/ml) and IFbeta-1a (1000 U/ml) for 24 h was followed by 48 h exposure to IFbeta-1a. We concluded that the blood-brain barrier endothelium may be a target of IFbeta-1a. Further, these in vitro findings may correlate with the results of recent clinical trials indicating that chronic treatment of relapsing remitting multiple sclerosis with IFbeta-1a prevents both clinical exacerbations and the appearance on Magnetic Resonance Imaging of new lesions enhanced by gadolinium which is taken up by increased transendothelial fluid phase vesicular transport.
|
Authors | G Defazio, M Trojano, D Ribatti, B Nico, M Giorelli, R De Salvia, G Russo, L Roncali, P Livrea |
Journal | Journal of neuroimmunology
(J Neuroimmunol)
Vol. 88
Issue 1-2
Pg. 13-20
(Aug 01 1998)
ISSN: 0165-5728 [Print] Netherlands |
PMID | 9688319
(Publication Type: Journal Article)
|
Chemical References |
- Tumor Necrosis Factor-alpha
- Intercellular Adhesion Molecule-1
- Interferon-beta
- Horseradish Peroxidase
- Interferon beta-1a
|
Topics |
- Animals
- Cells, Cultured
- Cerebrovascular Circulation
(drug effects, physiology)
- Endocytosis
(physiology)
- Endothelium, Vascular
(cytology, drug effects, metabolism)
- Horseradish Peroxidase
- Intercellular Adhesion Molecule-1
(metabolism)
- Interferon beta-1a
- Interferon-beta
(pharmacology)
- Male
- Microcirculation
(drug effects, physiology)
- Rats
- Rats, Wistar
- Tumor Necrosis Factor-alpha
(pharmacology)
|