title: Human pro-IL-1 beta gene expression in monocytic cells is regulated by two distinct pathways.
abstract: 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.
authors.affiliation: Harvard University-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge 02139.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fenton
authors.forename: M W
authors.initials: MW
authors.lastname: Vermeulen
authors.forename: B D
authors.initials: BD
authors.lastname: Clark
authors.forename: A C
authors.initials: AC
authors.lastname: Webb
authors.forename: P E
authors.initials: PE
authors.lastname: Auron
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D011498:Protein Precursors; C043830:interleukin 1 precursor; D013755:Tetradecanoylphorbol Acetate