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ICAM 1 expression and fluid phase endocytosis of cultured brain microvascular endothelial cells following exposure to interferon beta-1a and TNFalpha.

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.
AuthorsG Defazio, M Trojano, D Ribatti, B Nico, M Giorelli, R De Salvia, G Russo, L Roncali, P Livrea
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 88 Issue 1-2 Pg. 13-20 (Aug 01 1998) ISSN: 0165-5728 [Print] Netherlands
PMID9688319 (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)

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