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 J Toborek

Research output: Contribution to journalArticle

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

Fingerprint

Arachidonate 15-Lipoxygenase
Endothelial cells
Transcription
Interleukin-4
Human Umbilical Vein Endothelial Cells
Transcription Factors
Endothelial Cells
Genes
Chemical activation
GATA2 Transcription Factor
Assays
STAT6 Transcription Factor
NFI Transcription Factors
Electrophoretic mobility
Messenger RNA
Transcription factors
5' Flanking Region
Reticulocytes
Electrophoretic Mobility Shift Assay
LDL Lipoproteins

Keywords

  • Atherosclerosis
  • Cytokines
  • Oxidation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells. / Lee, Yong Woo; Kühn, Hartmut; Kaiser, Simone; Hennig, Bernhard; Daugherty, Alan; Toborek, Michal J.

In: Journal of Lipid Research, Vol. 42, No. 5, 15.06.2001, p. 783-791.

Research output: Contribution to journalArticle

Lee, YW, Kühn, H, Kaiser, S, Hennig, B, Daugherty, A & Toborek, MJ 2001, 'Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells', Journal of Lipid Research, vol. 42, no. 5, pp. 783-791.
Lee, Yong Woo ; Kühn, Hartmut ; Kaiser, Simone ; Hennig, Bernhard ; Daugherty, Alan ; Toborek, Michal J. / Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells. In: Journal of Lipid Research. 2001 ; Vol. 42, No. 5. pp. 783-791.
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