Human pro-IL-1 beta gene expression in monocytic cells is regulated by two distinct pathways.

We have previously reported that the pro-IL-1 beta gene is transiently expressed in THP-1 human monocytic leukemia cells after stimulation with bacterial LPS. Herein we show differential pro-IL-1 beta gene transcription in the same cell type using two distinct stimuli. This transcriptional difference is also reflected at the level of intracellular IL-1 beta protein production. In contrast to LPS, a phorbol ester (PMA) induces a stable, non-transient population of mRNA. Furthermore, each induction pathway is operational under conditions where the other is inhibited, suggesting functional independence. Evidence is presented for post-transcriptional regulation of the two responses in THP-1 cells at the level of mRNA stability. We also demonstrate a similar dualistic response in primary monocyte-derived human macrophages as well as the human myelocytic cell line HL-60.