Interleukin 6 Induces DNA Binding Activity of APi in Ml 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 this work. Ml myeloblastic cells were chosen for this purpose because of their high growth sensitivity to interleukin 6 (IL-6), transforming growth factor fl and a- and /3-interferons. It is reported here that IL-6 elevated the junB and c-jun mRNA levels and induced the formation of a novel DNA-protein complex with high sequence specificity to 1 2-O-tetradecanoylphorbol-l 3-acetate response element (TRE) oligonucleotides. This 11-6 induced TRE binding complex was abolished by anti-Jun specific antibodies and was efficiently competed by an oligonucleotide that comprises the mouse homologue of a previously described human c-myc negative DNA element. It persisted in cells for at least 48 h after 11-6 treatment and failed to be induced by a-and /3-interferons or by transforming growth factor fl, which affected differently the pattern of jun mRNA expression. To further explore regulatory and functional aspects of this induced TRE binding activity, an IL-6 resistant Ml clone was isolated and further analyzed. This clone carried a postreceptor deficiency that abrogated completely the growth inhibitory responses to IL-6 but did not interfere with the induction of two differentiation related cell surface markers. Interestingly, the 11-6 resistant clone had lost two molecular responses to 11-6, induction of TRE binding activity and suppression of the c-myc gene. The data correlate the 11-6 induced APi activity with the suppression of c-myc and growth inhibition