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Interleukin-1 beta increases leukemia inhibitory factor mRNA levels through transient stimulation of transcription
C D Carlson1, Y Bai, G M Jonakait
1Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA.
Insights
Interleukin-1 beta (IL-1 beta) increases leukemia inhibitor factor (LIF) mRNA in the superior cervical ganglion (SCG). While partly transcriptional, IL-1 beta likely also involves post-transcriptional regulation for LIF expression.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Interleukin-1 beta (IL-1 beta) is an inflammatory cytokine known to induce leukemia inhibitor factor (LIF) expression.
- LIF upregulation is often linked to cellular injury responses.
- The superior cervical ganglion (SCG) and Schwann cells are relevant models for studying neuro-inflammation and glial responses.
Purpose of the Study:
- To elucidate the molecular mechanisms by which IL-1 beta regulates LIF mRNA expression.
- To investigate the roles of IL-1 receptors, mRNA stability, and gene transcription in IL-1 beta-induced LIF upregulation.
- To compare LIF regulation by IL-1 beta in primary SCG explants and a Schwann cell line.
Main Methods:
- Primary neonatal rat SCG explants and an immortalized Schwann cell line were used.
- IL-1 beta treatment was applied, with interventions including soluble IL-1 receptors and IL-1 receptor antagonist.
- Dexamethasone was used to assess anti-inflammatory effects.
- Nuclear run-on assays were performed to measure LIF gene transcription rates.
- LIF mRNA decay was assessed by examining 3' AU-rich elements.
Main Results:
- IL-1 beta significantly increased LIF mRNA levels in SCG explants and Schwann cells.
- The induction of LIF mRNA by IL-1 beta was blocked by IL-1 receptor antagonists, confirming receptor involvement.
- Dexamethasone inhibited IL-1 beta-induced LIF mRNA upregulation.
- IL-1 beta did not increase LIF gene transcription in SCG explants at 6 or 24 hours.
- LIF gene transcription was rapidly and transiently induced in Schwann cells, returning to baseline by 1 hour.
Conclusions:
- IL-1 beta induction of LIF expression involves IL-1 receptors and is sensitive to anti-inflammatory agents like dexamethasone.
- The increase in LIF mRNA exceeds the transcriptional changes, suggesting significant post-transcriptional regulatory mechanisms are involved.
- While partially transcriptional, the regulation of LIF mRNA by IL-1 beta in these models is complex and likely involves post-transcriptional control.
Abstract:
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 beta increases LIF mRNA levels by interacting with IL-1 receptors in SCG, since this induction could be diminished by inclusion of either soluble IL-1 receptors or IL-1 receptor antagonist. The antiinflammatory glucocorticoid dexamethasone also inhibits LIF mRNA induction by IL-1 beta. 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 mechanism. IL-1 beta does not raise LIF gene transcription rate in cultured SCG 6 or 24 h after addition of IL-1 beta as measured by nuclear run-on assays. LIF gene transcription is induced repidly and transiently in an immortalized Schwann cell line, returning to uninduced rates by 1 h after induction. These results suggest that the IL-1 beta induction of LIF gene expression is at least partially transcriptional, but that LIF mRNA increases to a greater extent than LIF transcription, suggesting the possibility of posttranscriptional regulation as well.