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Journal of Lipid Research, Vol. 42, 783-791, May 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

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

Correspondence to: Michal Toborek, To whom correspondence should be addressed., mjtobo00{at}pop.uky.edu (E-mail)

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 posttranscriptional levels. — Lee, Y. W., H. Kühn, S. Kaiser, B. Hennig, A. Daugherty, and M. Toborek. Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells. J. Lipid Res. 2001. 42: 783;–791.

Supplementary key words: cytokines, atherosclerosis, oxidation, transcriptional regulation

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