Transcriptional regulation of the human prointerleukin 1 beta gene

Interleukin 1 (IL 1) is a protein produced by monocytes in response to certain antigens which produces a wide variety of cellular responses in various tissues. We have studied the regulation of the human proIL-1 beta gene in THP-1 human monocytic leukemia cells. Lipopolysaccharide (LPS) induction of this gene results in an immediate and transient increase of message that rapidly falls to a low, but constant, level within 6 hr. This decrease results from a specific repression of transcription by 2 hr after stimulation. Cycloheximide inhibition of new protein synthesis causes a superinduction of IL 1 message, but does not alter the initial kinetics of message production. This presumably delays the synthesis of a labile transcriptional repressor protein and implies that the proIL-1 beta gene is under the control of both a transcriptional activator and a newly synthesized transcriptional repressor. The transient increase in mRNA production and the sustained low-level synthesis beyond the initial transient response suggest that the IL 1 protein itself may act intracellularly in a manner analogous to that described for several proto-oncogenes and cellular competence factors.