Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 11 January 1991:
Vol. 251. no. 4990, pp. 204 - 207
DOI: 10.1126/science.1898993
Prev | Table of Contents | Next

Articles

Science, Vol 251, Issue 4990, 204-207
Copyright © 1991 by American Association for the Advancement of Science

articles

Signal transduction by interferon-alpha through arachidonic acid metabolism

GE Hannigan and BR Williams

Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.

Molecular mechanisms that mediate signal transduction by growth inhibitory cytokines are poorly understood. Type I (alpha and beta) interferons (IFNs) are potent growth inhibitory cytokines whose biological activities depend on induced changes in gene expression. IFN-alpha induced the transient activation of phospholipase A2 in 3T3 fibroblasts and rapid hydrolysis of [3H]arachidonic acid (AA) from prelabeled phospholipid pools. The phospholipase inhibitor, bromophenacyl bromide (BPB), specifically blocked IFN-induced binding of nuclear factors to a conserved, IFN-regulated enhancer element, the interferon-stimulated response element (ISRE). BPB also caused a dose-dependent inhibition of IFN-alpha-induced ISRE-dependent transcription in transient transfection assays. Specific inhibition of AA oxygenation by eicosatetraynoic acid prevented IFN-alpha induction of factor binding to the ISRE. Treatment of intact cells with inhibitors of fatty acid cyclooxygenase or lipoxygenase enzymes resulted in amplification of IFN-alpha-induced ISRE binding and gene expression. Thus, IFN-alpha receptor-coupled AA hydrolysis may function in activation of latent transcription factors by IFN-alpha and provides a system for studying the role of AA metabolism in transduction of growth inhibitory signals.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Control of cyclic AMP concentration in bovine endometrial stromal cells by arachidonic acid.
Z Cheng, E L Sheldrick, E Marshall, D C Wathes, D R E Abayasekara, and A P F Flint (2007)
Reproduction 133, 1017-1026
   Abstract »    Full Text »    PDF »
Evidence That Arachidonate 15-Lipoxygenase 2 Is a Negative Cell Cycle Regulator in Normal Prostate Epithelial Cells.
S. Tang, B. Bhatia, C. J. Maldonado, P. Yang, R. A. Newman, J. Liu, D. Chandra, J. Traag, R. D. Klein, S. M. Fischer, et al. (2002)
J. Biol. Chem. 277, 16189-16201
   Abstract »    Full Text »    PDF »
Induction of PG G/H Synthase-2 in Bovine Myometrial Cells by Interferon-{tau} Requires the Activation of the p38 MAPK Pathway.
F. Doualla-Bell and A. E. Koromilas (2001)
Endocrinology 142, 5107-5115
   Abstract »    Full Text »    PDF »
The disabled dendritic cell.
M. THURNHER, C. ZELLE-RIESER, R. RAMONER, G. BARTSCH, and L. HOLTL (2001)
FASEB J 15, 1054-1061
   Abstract »    Full Text »    PDF »
Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures.
S. Goodbourn, L. Didcock, and R. E. Randall (2000)
J. Gen. Virol. 81, 2341-2364
   Full Text »
Interferon-alpha 2b combined with daily ketoprofen administration improves virological response in chronic hepatitis C: a prospective and randomised trial.
A E Munoz, D Levi, A Podesta, J M. Gorin, J Gonzalez, M A Bartellini, M S Munne, A Cabanne, D Flichman, and R Terg (2000)
Gut 46, 427-431
   Abstract »    Full Text »    PDF »
Both (n-3) and (n-6) Fatty Acids Stimulate Wound Healing in the Rat Intestinal Epithelial Cell Line, IEC-6.
D. J. Ruthig and K. A. Meckling-Gill (1999)
J. Nutr. 129, 1791-1798
   Abstract »    Full Text »
Arachidonic acid mediates interferon-gamma-induced sphingomyelin hydrolysis and monocytic marker expression in HL-60 cell line.
D Visnjic, D Batinic, and H Banfic (1997)
Blood 89, 81-91
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)