Induction of Rapid IL-β mRNA Degradation in THP-1 Cells Mediated Through the AU-Rich Region in the 3′UTR by a Radicicol Analogue

A radicicol analogue (analogue A) was found to inhibit interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (tnf-α) secretion from THP-1 cells. If added to cells activated by interferon gamma and lipopolysaccharide, radicicol analogue A not only inhibited the secretion of IL-1β but also induc...

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Veröffentlicht in:Cytokine (Philadelphia, Pa.) Pa.), 1996-10, Vol.8 (10), p.751-761
Hauptverfasser: Kastelic, Tania, Schnyder, Jög, Leutwiler, Albert, Traber, René, Streit, Bruno, Niggli, Heinz, MacKenzie, Andrew, Cheneval, Dominique
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Sprache:eng
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Zusammenfassung:A radicicol analogue (analogue A) was found to inhibit interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (tnf-α) secretion from THP-1 cells. If added to cells activated by interferon gamma and lipopolysaccharide, radicicol analogue A not only inhibited the secretion of IL-1β but also induced an extremely rapid degradation of IL-1β, IL-6 and TNF-α mRNA to undetectable levels within 5–8 h. This degradation is independent of translation and of the signal inducing transcription. The common feature of these genes is the inclusion of one or more copies of the mRNA-instability sequence, AUUUA, in the 3′ untranslated region. Indeed, no destabilizing effect of radicicol analogue A could be observed on mRNA derived from the expression of an IL-1β construct lacking the AUUUA motifs of the 3′UTR. the effect of radicicol analogue A on protein/mRNA interaction and on post-translational modifications of cytoplasmic proteins is described. This class of compound constitutes a valuable tool for the further elucidation of the mechanism of mRNA degradation of cytokines and proto-oncogenes.
ISSN:1043-4666
1096-0023
DOI:10.1006/cyto.1996.0100