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.
Fenton
M J
MJ
Harvard University-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge 02139.
Vermeulen
M W
MW
Clark
B D
BD
Webb
A C
AC
Auron
P E
PE
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
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011498:Protein Precursors; C043830:interleukin 1 precursor; D013755:Tetradecanoylphorbol Acetate