INTERLEUKIN-6 INDUCES DNA-BINDING ACTIVITY OF AP1 IN M1 MYELOBLASTIC CELLS BUT NOT IN A GROWTH RESISTANT CELL DERIVATIVE

The effects that three different growth inhibitory cytokines exert on expression and function of members of the Jun family were studied in t his work. M1 myeloblastic cells were chosen for this purpose because o f their high growth sensitivity to interleukin 6 (IL-6), transforming growth factor beta1 and alpha- and beta-interferons. It is reported he re that IL-6 elevated the junB and c-jun mRNA levels and induced the f ormation of a novel DNA-protein complex with high sequence specificity to 12-0-tetradecanoylphorbol-13-acetate response element (TRE) oligon ucleotides. This IL-6 induced TRE binding complex was abolished by ant i-Jun specific antibodies and was efficiently competed by an oligonucl eotide that comprises the mouse homologue of a previously described hu man c-myc negative DNA element. It persisted in cells for at least 48 h after IL-6 treatment and failed to be induced by alpha- and beta-int erferons or by transforming growth factor beta1, which affected differ ently the pattern of jun mRNA expression. To further explore regulator y and functional aspects of this induced TRE binding activity, an IL-6 resistant M1 clone was isolated and further analyzed. This clone carr ied a postreceptor deficiency that abrogated completely the growth inh ibitory responses to IL-6 but did not interfere with the induction of two differentiation related cell surface markers. Interestingly, the I L-6 resistant clone had lost two molecular responses to IL-6, inductio n of TRE binding activity and suppression of the c-myc gene. The data correlate the IL-6 induced AP1 activity with the suppression of c-myc and growth inhibition.