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KMID : 0613820090190070949
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Journal of Life Science
2009 Volume.19 No. 7 p.949 ~ p.955
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Role of PKR and EGR-1 in Induction of Interleukin-8 by Type B Trichothecene Mycotoxin Deoxynivalenol in the Human Intestinal Epithelial Cells
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Park Seong-Hwan
Yang Hyun
Choi Hye-Jin
Park Yeong-Min
Ahn Soon-Cheol
Kim Kwan-Hoi
Lee Soo-Hyung
Ahn Jung-Hoon
Chung Duck-Hwa
Moon Yu-Seok
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Abstract
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Mucosal epithelia sense external stress signals and transmit them to the intracellular cascade responses. Ribotoxic stress-producing chemicals such as deoxynivalenol (DON) or other trichothecene mycotoxins have been linked with gastrointestinal inflammatory diseases by Fusarium-contamination. The purpose of this study was to test the hypothesis that DON evokes the epithelial sentinel signals of RNA-dependent protein kinase (PKR) and early growth response gene 1 (EGR-1), which together contribute to the pro-inflammatory cytokine interleukin 8 (IL-8) in human intestinal epithelial cells. PKR suppression by the dominant negative PKR expression attenuated DON-stimulated interleukin-8 production. Moreover, IL-8 transcriptional activation by DON was also reduced by PKR inhibition in the human intestinal epithelial cells. Treatment with the PKR inhibitor also suppressed EGR-1 promoter activity, mRNA and protein induction, although mitogen-activated protein (MAP) kinases such as extracellular signal-regulated protein kinases (ERK) 1/2, p38, c-Jun N-terminal Kinase (JNK) were little affected or even enhanced in presence of a PKR inhibitor. These patterns were also compared in the EGR-1-suppressed cells, which showed much more suppressed production of IL-8. All things taken into consideration, DON-activated sentinel signals of EGR-1 via PKR mediated interleukin-8 production in human intestinal epithelial cells, which provide insight into the possible general mechanism associated with mucosal inflammation as an intestinal toxic insult by ribotoxic trichothecene mycotoxins.
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KEYWORD
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Ribotoxic stress, deoxynivalenol, gastrointestinal inflammation, interleukin-8
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