ICAM 1 expression and fluid phase endocytosis of cultured brain microvascular endothelial cells following exposure to interferon beta-1a and TNFalpha.
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.
Defazio
G
G
Institute of Neurology, University of Bari, Italy.
Trojano
M
M
Ribatti
D
D
Nico
B
B
Giorelli
M
M
De Salvia
R
R
Russo
G
G
Roncali
L
L
Livrea
P
P
D000818:Animals; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006735:Horseradish Peroxidase; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta; D006735:Horseradish Peroxidase; D000068556:Interferon beta-1a