Arachidonic acid regulates the binding of human interferon in human skin fibroblasts.
The induction of the antiviral state in human fibroblasts by human interferon is inhibited by arachidonic acid, its analogues 5,8,11,14-eicosatetraynoic and 5,8,11-eicosatriynoic acids, as well as by sodium arachidonate. The fatty acids myristic or oleic acid and sodium palmitate do not inhibit the antiviral action of interferon. Experiments were conducted to investigate the mechanism by which arachidonic acid could inhibit the action of interferon. No correlation between cellular lipoxygenase activities and the inhibition of antiviral action of interferon was observed in the fatty acid treated cells. Likewise, the cyclooxygenase inhibitors indomethacin and oxyphenylbutazone do not inhibit the interferon-induced antiviral state. Taken together, the inhibition of interferon action by arachidonates is unlikely to be mediated by cyclooxygenase or lipoxygenase-generated intermediates, even though arachidonates are known to affect the activity of these enzymes in vitro. Measurement of interferon receptors in the fatty acid treated cells showed that arachidonic acid, sodium arachidonate and its analogues decreased the number of human type I interferon receptors available for binding, and inhibited the transcription of the interferon-induced 6-16 gene and the induction of cellular (2'-5')-oligoadenylate synthetase, suggesting the mechanism of inhibition is mediated at the level of the interferon receptor. The significance of the finding that arachidonic acid, a common fatty acid of cells and serum, can affect the antiviral action of interferon is discussed.
Institute of Molecular and Cell Biology, National University of Singapore.
S D
SD
Menon
W H
WH
Yap
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A
Lim
Y H
YH
Tan
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D000077190:Interferon alpha-2; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta; D008084:Lipoxygenase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014762:Viral Interference / Q000187:drug effects*
D001095:Arachidonic Acids; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D012313:RNA; D016899:Interferon-beta; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015088:2',5'-Oligoadenylate Synthetase; D000068556:Interferon beta-1a