PMID: 9166751Jun 1, 1997Paper

Pretreatment of astrocytes with interferon-alpha/beta impairs interferon-gamma induction of nitric oxide synthase

Journal of Neurochemistry
V C StewartS J Heales

Abstract

Excessive nitric oxide/peroxynitrite generation has been implicated in the pathogenesis of multiple sclerosis, and the demonstration of increased astrocytic nitric oxide synthase activity in the postmortem brain of multiple sclerosis patients supports this hypothesis. Exposure of astrocytes, in primary culture, to interferon-gamma results in stimulation of nitric oxide synthase activity and increased nitric oxide release. In contrast to interferon-gamma, interferon-alpha/beta had a minimal effect on astrocytic nitric oxide formation. Furthermore, pretreatment of astrocytes with interferon-alpha/beta inhibited (approximately 65%) stimulation by interferon-gamma of nitric oxide synthase activity and nitric oxide release. Treatment with interferon-alpha/beta at a concentration as low as 10 U/ml caused inhibition of mitochondrial cytochrome c oxidase. Furthermore, the damage to cytochrome c oxidase was prevented by the putative interferon-alpha/beta receptor antagonist oxyphenylbutazone. In view of these observations, our current hypothesis is that the mitochondrial damage caused by exposure to interferon-alpha/beta may impair the ability of astrocytes to induce nitric oxide synthase activity on subsequent interferon-gamma exposure...Continue Reading

Citations

Oct 22, 2008·The International Journal of Neuroscience·Münire Kilinç ToprakMuhtesem Ağildere
Oct 17, 2009·Nanotechnology·Daniele VergaraRoss Rinaldi
Feb 16, 1999·Brain Pathology·K J SmithP A Felts
Oct 8, 1998·Multiple Sclerosis : Clinical and Laboratory Research·G GiovannoniE J Thompson
Sep 2, 1998·Current Opinion in Neurology·R S Liblau, B Fontaine
Nov 19, 2003·The European Journal of Neuroscience·Sabine GoldeAlastair Compston
Aug 19, 2007·Neuroimmunomodulation·Olga BarcaVíctor M Arce
Nov 24, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·A Créange
Oct 3, 2012·Journal of the Neurological Sciences·Ivana StojanovicMaja Stukalov
Jan 25, 2003·Free Radical Biology & Medicine·Victoria C Stewart, Simon J R Heales

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