Elsewhere reviews. Interferon signalling through arachidonic acid-dependent pathways: A clue to adjuvant therapy for chronic viral hepatitis?
✍ Scribed by Gordon Baskin
- Book ID
- 102239249
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 400 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Molecular mechanisms that mediate signal transduction by growth inhibitory cytokines are poorly understood. Type I (a and p) interferons (IFNs) are potent growth inhibitory cytokines whose biological activities depend on induced changes in gene expression. IFN-a induced transient activation of phospholipase A, in 3T3 fibroblasts and rapid hydrolysis of [3H]-arachidonic acid (AA) from prelabeled phospholipid pools. The phospholipase inhibitor, bromophenacyl bromide (BPB), specifically blocked IFNinduced binding of nuclear factors to a conserved, IFN-regulated enhancer element, the interferonstimulated response element (ISRE). BPB also caused a dose-dependent inhibition of IFN-a-stimulated ISREdependent transcription in transient transfection assays. Specific inhibition of AA oxidation by eicosatetraynoic acid prevented IFN-cu induction of factors binding to ISRE. Treatment of intact cells with inhibitors of fatty acid cyclooxygenase or lipoxygenase enzymes resulted in amplification of IFN-a-induced ISRE binding and gene expression. Thus, IFN-a receptor-coupled AA hydrolysis may function in activation of latent factors by IFN-a and provides a system for studying the role of AA metabolism in transduction of growth inhibitory signals.