Synergism between protein‐kinase C and cAMP‐dependent pathways in the expression of the interleukin‐1β gene is mediated via the activator‐protein‐1 (AP‐1) enhancer activity

摘要: In many different cell types treatment with phorbol esters (e.g. 4β-phorbol 12-myristate 13-acetate, PMA) leads to the activation of protein-kinase C (PKC) and subsequently activator-protein-1(AP-1)-responsive gene expression. We have previously reported that a structural analog cAMP (dibutyryl cAMP, Bt2cAMP) or agents elevating endogenous levels strongly enhanced PMA-induced interleukin-1β(IL-1β)-gene expression in human myeloid leukemia cells (THP-1, HL-60). now examined role AP-1 regulation IL-1β by PKC THP-1 cells. is complex composed products jun fos families. Our studies show Bt2cAMP enhances c-fos jun-B expression, but inhibits c-jun Electrophoretic mobility-shift assay revealed also increased DNA-binding activity. The functional activity was studied transfecting reporter constructs containing sites [Col-TREx5/TK-CAT IL-1β-X-CAT, which contains putative 12-O-tetradecanoyl-phorbol-13-acetate(TPA)-responsive element gene]. Transient transfection demonstrated similarily transcription from both these constructs. Taken together, results suggest increases then