INTERLEUKIN-1-BETA INCREASES LEUKEMIA INHIBITORY FACTOR MESSENGER-RNALEVELS THROUGH TRANSIENT STIMULATION OF TRANSCRIPTION RATE

Interleukin-1 beta (IL-1 beta) induces leukemia inhibitor factor (LIF) expression in a number of cell types including non-neuronal cells of the sympathetic superior cervical ganglion (SCG). Upregulation of LIF by inflammatory cytokines is usually associated with injury response. We characterized the molecular mechanism of LIF mRNA regulation by IL- 1 beta in explanted neonatal rat SCG and a Schwann cell line. IL-1 bet a increases LIF mRNA levels by interacting with IL-1 receptors in SCG, since this induction could be diminished by inclusion of either solub le IL-1 receptors or IL-1 receptor antagonist. The antiinflammatory gl ucocorticoid dexamethasone also inhibits LIF mRNA induction by IL-1 be ta. LIF mRNA encodes a 3' AU-rich mRNA stability control sequence, but IL-1 beta does not appear to regulate the decay of LIF mRNA by this m echanism. IL-1 beta does not raise LIF gene transcription rate in cult ured SCG 6 or 24 h after addition of IL-1 beta as measured by nuclear run-on assays. LIF gene transcription is induced rapidly and transient ly in an immortalized Schwann cell line, returning to uninduced rates by 1 h after induction. These results suggest that the IL-1 beta induc tion of LIF gene expression is at least partially transcriptional, but that LIF mRNA increases to a greater extent than LIF transcription, s uggesting the possibility of posttranscriptional regulation as well. ( C) 1996 Wiley-Liss, Inc.