Regulation of tumor necrosis factor gene expression by ionizing radiation in human myeloid leukemia cells and peripheral blood monocytes

Matthew L. Sherman, Rakesh Datta, Dennis E. Hallahan, Ralph R. Weichselbaum, Donald W. Kufe

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

Previous studies have demonstrated that ionizing radiation induces the expression of certain cytokines, such as TNF α/cachectin. However, there is presently no available information regarding the molecular mechanisms responsible for the regulation of cytokine gene expression by ionizing radiation. In this report, we describe the regulation of the TNF gene by ionizing radiation in human myeloid leukemia cells. The increase in TNF transcripts by x rays was both time- and dose-dependent as determined by Northern blot analysis. Similar findings were obtained in human peripheral blood monocytes. Transcriptional run-on analyses have demonstrated that ionizing radiation stimulates the rate of TNF gene transcription. Furthermore, induction of TNF mRNA was increased in the absence of protein synthesis. In contrast, ionizing radiation had little effect on the half-life of TNF transcripts. These findings indicate that the increase in TNF mRNA observed after irradiation is regulated by transcriptional mechanisms and suggest that production of this cytokine by myeloid cells may play a role in the pathophysiologic effects of ionizing radiation.

Original languageEnglish
Pages (from-to)1794-1797
Number of pages4
JournalJournal of Clinical Investigation
Volume87
Issue number5
DOIs
StatePublished - May 1991

Keywords

  • Gene expression
  • Ionizing radiation
  • Monocytes
  • TNF
  • Transcription

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