Abstract
Polymorphonuclear leukocytes (PMN) play an important role in inflammation, immune responses, and tissue repair by secreting interleukin-1β (IL-1β). We investigated the regulation of IL-1β gene expression in human PMN treated with granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF induced IL-1β mRNA accumulation at 0.1 ng/ml and maximal induction was observed at 1 ng/ml. IL-1β mRNA levels reached a maximum within 1-2 h after stimulation with GM-CSF and returned to baseline levels by 4-6 h. The time course of IL-1β mRNA induction by GM-CSF was more protracted than previously reported for PMN stimulated with tumor necrosis factor-α (TNF-α, 10 ng/ml). Nuclear run-on analysis indicated that GM-CSF, like TNF, increases IL-1β transcription. Kinetic studies with the RNA synthesis inhibitor, actinomycin D, showed that GM-CSF induces stable IL-1β mRNA. Cycloheximide enhanced the IL-1β mRNA accumulation by GM-CSF at the level of mRNA stabilization, but blocked IL-1β mRNA expression by TNF. Thus, GM-CSF increases IL-1β message accumulation in PMN at both the transcriptional and post-transcriptional levels by mechanisms that are different from TNF induction of IL-1β gene expression.
Original language | English (US) |
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Pages (from-to) | 598-603 |
Number of pages | 6 |
Journal | Journal of Leukocyte Biology |
Volume | 59 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1996 |
Externally published | Yes |
Keywords
- Inflammation
- Neutrophil
- mRNA stabilization
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology