INTERLEUKIN-1 ACTIVATION OF THE AP-1 TRANSCRIPTION COMPLEX IN MURINE T-CELLS IS REGULATED AT THE LEVEL OF JUN-B PROTEIN ACCUMULATION

We have examined the regulation of the AP-1 DNA transcription complex during T cell activation in response to interleukin 1 (IL-1) and phorb ol ester (TPA) treatment of the IL-1 responsive murine thymoma T cell line, EL46.1 C 10. IL-1 synergistically enhances the stimulatory effec t of TPA on AP-1-mediated gene expression in this cell line. To elucid ate the mechanism(s) by which IL-1 enhances AP-1-mediated gene express ion, we examined the effect of IL-1 on the synthesis and turnover of J un B, the member of the jun gene family that is present in AP-1 comple xes in EL4 cells. We found that IL-1 + TPA-treated cells contain signi ficantly higher Jun B protein levels than cells treated with TPA alone . IL-1 promotes the prolonged accumulation of Jun B, whereas the cellu lar content of Jun B decreases dramatically after 6 hr in cells treate d with only TPA. IL-1 enhancement of Jun B protein levels is not the r esult of a change in the turnover rate of the Jun B protein, but rathe r results from the maintenance of sufficient jun B mRNA to support con tinued accumulation of newly synthesized protein. In addition to Jun B , we found that the T cell AP-1 complex contains the Fra-1 protein, a member of the fos gene family. Although IL-1 dramatically increases Ju n B accumulation, it does not enhance TPA-induced Fra-1 protein levels in EL4 cells. Thus, the stimulation of AP-1-mediated gene expression by IL-1 in EL4 cells is due to the promotion of Jun B protein accumula tion that, in turn, facilitates Jun B heterodimerization with TPA-indu ced Fra-1 protein, thereby forming an active AP-1 complex.