Journal of Lipid Research | |
Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells | |
Bernhard Hennig1  Alan Daugherty2  Simone Kaiser3  Yong Woo Lee3  Michal Toborek4  Hartmut Kühn5  | |
[1] University of Potsdam, 14469 Potsdam, Germany;Department of Nutrition and Food Science, University of Kentucky Medical Center, Lexington, KY 40536;Department of Surgery, University of Kentucky Medical Center, Lexington, KY 40536;Gill Heart Institute, University of Kentucky Medical Center, Lexington, KY 40536;Humboldt University, 10115 Berlin, Germany; | |
关键词: cytokines; atherosclerosis; oxidation; transcriptional regulation; | |
DOI : | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown