Transcriptional and post-transcriptional regulation of GM-CSF-induced IL-1β gene expression in PMN

Marilyn C. Fernandez, John Walters, Phillip Marucha

Research output: Contribution to journalArticle

20 Scopus citations

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 languageEnglish (US)
Pages (from-to)598-603
Number of pages6
JournalJournal of Leukocyte Biology
Volume59
Issue number4
DOIs
StatePublished - Apr 1996

Keywords

  • Inflammation
  • Neutrophil
  • mRNA stabilization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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