PROTEIN-SYNTHESIS INHIBITORS CYCLOHEXIMIDE AND ANISOMYCIN INDUCE INTERLEUKIN-6 GENE-EXPRESSION AND ACTIVATE TRANSCRIPTION FACTOR NF-KAPPA-B

In two human cell lines, MDA-MB-231 and HeLa, the inducible expression of the interleukin-6 (IL-6) gene by two protein synthesis inhibitors, cycloheximide and anisomycin, was compared with the induction by the most potent physiological inducer of IL-6 described to date, interleuk in-1 beta (IL-1 beta). In cycloheximide or anisomycin treated cells, t he accumulation of the IL-6 message and the activation of transcriptio n factors required for IL-6 gene expression occurs at an extent simila r to that obtained with IL-1 beta. Furthermore, IL-6 mRNA accumulation stimulated by cycloheximide or anisomycin is almost completely inhibi ted in the presence of actinomycin D, indicating that this effect occu rs mainly through the activation of the transcriptional machinery. The se data indicate that transcriptional induction of the IL-6 gene by in hibitors of protein synthesis is triggered by the same nuclear signals as other inducers. (C) 1997 Academic Press.