TY - JOUR
T1 - Transcriptional and post-transcriptional regulation of GM-CSF-induced IL-1β gene expression in PMN
AU - Fernandez, Marilyn C.
AU - Walters, John
AU - Marucha, Phillip
PY - 1996/4
Y1 - 1996/4
N2 - 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.
AB - 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.
KW - Inflammation
KW - Neutrophil
KW - mRNA stabilization
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U2 - 10.1002/jlb.59.4.598
DO - 10.1002/jlb.59.4.598
M3 - Article
C2 - 8613710
AN - SCOPUS:0029889216
VL - 59
SP - 598
EP - 603
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 4
ER -