Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells

Yong Woo Lee, Hartmut Kühn, Simone Kaiser, Bernhard Hennig, Alan Daugherty, Michal Toborek

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Abstract

The reticulocyte-type 15-lipoxygenase (15-LO-I) has been implicated in atherogenesis because of its capability of oxidizing low density lipoprotein. Therefore, we investigated the expression of the 15-LO-I gene in human umbilical vein endothelial cells (HUVEC). Nonactivated HUVEC did not exhibit detectable 15-LO-I mRNA. However, exposure of the cells to interleukin 4 (IL-4) induced the transcription of the 15-LO-I gene in a time- and concentration-dependent manner. Interestingly, this induction was not paralleled by a concomitant production of the functional 15-LO-I enzyme, as indicated by activity assays and immunoblotting. To gain more information about the mechanism of the induction process, we investigated IL-4-dependent activation of nuclear transcription factors for which binding sites were previously identified in the 5′-flanking region of the human 15-LO-I gene. Electrophoretic mobility shift assays revealed that IL-4 can activate signal transducer and activator of transcription 6, activator protein 2, GATA motif-binding transcription factor 1, nuclear factor 1, and SP-1 in HUVEC in a time- and concentration-dependent manner. Activation of these transcription factors was observed as early as 30 min after cytokine exposure. These data indicate that IL-4 upregulates the transcription of the 15-LO-I gene in human vascular endothelial cells, and this process may involve the activation of several nuclear transcription factors. The lack of active 15-LO-I protein in the presence of functional 15-LO-I mRNA suggests additional regulatory elements of 15-LO expression at post-transcriptional levels.

Original languageEnglish (US)
Pages (from-to)783-791
Number of pages9
JournalJournal of Lipid Research
Volume42
Issue number5
StatePublished - Jun 15 2001
Externally publishedYes

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Keywords

  • Atherosclerosis
  • Cytokines
  • Oxidation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Lee, Y. W., Kühn, H., Kaiser, S., Hennig, B., Daugherty, A., & Toborek, M. (2001). Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells. Journal of Lipid Research, 42(5), 783-791.