[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5352/JLS.2009.19.7.949

Role of PKR and EGR-1 in Induction of Interleukin-S by Type B Trichothecene Mycotoxin Deoxynivalenol in the Human Intestinal Epithelial Cells

Park, Seong-Hwan (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)
Yang, Hyun (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)
Choi, Hye-Jin (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)
Park, Yeong-Min (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)
Ahn, Soon-Cheol (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)
Kim, Kwan-Hoi (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)
Lee, Soo-Hyung (Microbial Safety Division, Department of Crop Life Safety, National Academy of Agricultural Science, Rural Development Administration)
Ahn, Jung-Hoon (Korea Science Academy)
Chung, Duk-Hwa (Division of Applied Life Science, Graduate School of Gyeongsang National University)
Moon, Yu-Seok (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)

Publication Information

Journal of Life Science / v.19, no.7, 2009 , pp. 949-955 More about this Journal

Abstract

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, 1L-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 (INK) 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 1L-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.

Keywords

Ribotoxic stress; deoxynivalenol; gastrointestinal inflammation; interleukin-8;

Citations & Related Records

Reference

1	Tam, C. L., M. Hofbauer, and C. A. Towle. 2007. Requirement for protein kinase R in interleukin-1alpha-stimulated effects in cartilage. Biochem. Pharmacol. 74, 1636-1641 DOI ScienceOn
2	Ueno, Y. 1970. Toxicity and action mechanism of mycotoxin. Nippon Saikingaku Zasshi 25, 420
3	Vijay-Kumar, M., J. R. Gentsch, W. J. Kaiser, N. Borregaard, M. K. Offermann, A. S. Neish, and A. T. Gewirtz. 2005. Protein kinase R mediates intestinal epithelial gene remodeling in response to double-stranded RNA and live rotavirus. J. Immunol. 174, 6322-6331 DOI
4	Wong, W. M., R. J. Playford, and N. A. Wright. 2000. Peptide gene expression in gastrointestinal mucosal ulceration: ordered sequence or redundancy? Gut 46, 286-292 DOI ScienceOn
5	Yan, S. F., Y. S. Zou, Y. Gao, C. Zhai,N. Mackman, S. L. Lee, J. Milbrandt, D. Pinsky, W. Kisiel, and D. Stern. 1998. Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia. Proc. Natl. Acad. Sci. USA 95, 8298-8303 DOI ScienceOn
6	Zhou, H. R., J. R. Harkema, D. Yan, and J. J. Pestka. 1999. Amplified proinflammatory cytokine expression and toxicity in mice coexposed to lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol). J. Toxicol. Environ. Health A 57, 115-136 DOI
7	Zhou, H. R., Q. Jia, and J. J. Pestka. 2005. Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase Hck. Toxicol. Sci. 85, 916-926 DOI ScienceOn
8	Murphy, L. O., J. P. MacKeigan, and J. Blenis. 2004. A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude and duration. Mol. Cell Biol. 24, 144-153 DOI ScienceOn
9	Peraica, M. and A. M. Domijan. 2001. Contamination of food with mycotoxins and human health. Arh. Hig. Rada. Toksikol. 52, 23-35
10	Pestka, J. J. and A. T. Smolinski. 2005. Deoxynivalenol: toxicology and potential effects on humans. J. Toxicol. Environ. Health B Crit. Rev. 8, 39-69 DOI ScienceOn
11	Shkoda, A., P. A. Ruiz, H. Daniel, S. C. Kim, G. Rogler, R. B. Sartor, and D. Haller. 2007. Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Gastroenterology 132, 190-207 DOI ScienceOn
12	Rotter, B. A., D. B. Prelusky, and J. J. Pestka. 1996. Toxicology of deoxynivalenol (vomitoxin). J. Toxicol. Environ. Health 48, 1-34 DOI ScienceOn
13	Shi, Y. and J. J. Pestka. 2008. Mechanisms for suppression of interleukin-6 expression in peritoneal macrophages from docosahexaenoic acid-fed mice. J. Nutr. Biochem. [Epub ahead of print]
14	Shifrin, V. I. and P. Anderson. 1999. Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis. J. Biol. Chem. 274, 13985-13992 DOI ScienceOn
15	Sudakin, D. L. 2003. Trichothecenes in the environment: relevance to human health. Toxicol. Lett. 143, 97-107 DOI ScienceOn
16	Szabo, S., X. Deng, T. Khomenko, M. Yoshida, M. R. Jadus, Z. Sandor, Z. Gombos, and H. Matsumoto. 2001. Gene expression and gene therapy in experimental duodenal ulceration. J. Physiol. Paris 95, 325-335 DOI ScienceOn
17	Levkovitz, Y. and J. M. Baraban. 2002. A dominant negative Egr inhibitor blocks nerve growth factor-induced neurite outgrowth by suppressing c-Jun activation: role of an Egr/c-Jun complex. J. Neurosci. 22, 3845-3854
18	Li, F. Q., Y. W. Li, X. Y. Luo, and T. Yoshizawa. 2002. Fusarium toxins in wheat from an area in Henan Province, PR China, with a previous human red mould intoxication episode. Food Addit. Contam. 19, 163-167
19	Milbrandt, J. 1987. A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science 238, 797-799 DOI
20	Li, M., J. R. Harkema, C. F. Cuff, and J. J. Pestka. 2007. Deoxynivalenol exacerbates viral bronchopneumonia induced by respiratory reovirus infection. Toxicol. Sci. 95, 412-426 DOI ScienceOn
21	Mirocha, C. J., S. V. Pathre, B. Schauerhamer, and C. M. Christensen. 1976. Natural occurrence of Fusarium toxins in feedstuff. Appl. Environ. Microbiol. 32, 553-556
22	Mishra, J. P., S. Mishra, K. Gee, and A. Kumar. 2005. Differential involvement of calmodulin-dependent protein kinase II-activated AP-1 and c-Jun N-terminal kinase- activated EGR-1 signaling pathways in tumor necrosis factor-alpha and lipopolysaccharide-induced CD44 expression in human monocytic cells. J. Biol. Chem. 280, 26825-26837 DOI ScienceOn
23	Moon, Y. and J. J. Pestka. 2002. Vomitoxin-induced cyclooxygenase- 2 gene expression in macrophages mediated by activation of ERK and p38 but not JNK mitogen-activated protein kinases. Toxicol. Sci. 69, 373-382 DOI ScienceOn
24	Moon, Y., H. Yang, and S. H. Lee. 2007. Modulation of early growth response gene 1 and interleukin-8 expression by ribotoxin deoxynivalenol (vomitoxin) via ERK1/2 in human epithelial intestine 407 cells. Biochem. Biophys. Res. Commun. 362, 256-262 DOI ScienceOn
25	Giri, R. K., S. K. Selvaraj, and V. K. Kalra. 2003. Amyloid peptide-induced cytokine and chemokine expression in THP-1 monocytes is blocked by small inhibitory RNA duplexes for early growth response-1 messenger RNA. J. Immunol. 170, 5281-5294 DOI
26	Islam, Z., J. S. Gray, and J. J. Pestka. 2006. p38 Mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes. Toxicol. Appl. Pharmacol. 213, 235-244 DOI ScienceOn
27	Gray, J. S., H. K. Bae, J. C. Li, A. S. Lau, and J. J. Pestka. 2008. Double-stranded RNA-activated protein kinase mediates induction of interleukin-8 expression by deoxynivalenol, Shiga toxin 1, and ricin in monocytes. Toxicol. Sci. 105, 322-330 DOI ScienceOn
28	Grotegut, S., D. von Schweinitz, G. Christofori, and F. Lehembre. 2006. Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail. Embo. J. 25, 3534-3545 DOI ScienceOn
29	Iordanov, M. S., R. J. Choi, O. P. Ryabinina, T. H. Dinh, R. K. Bright, and B. E. Magun. 2002. The UV (Ribotoxic) stress response of human keratinocytes involves the unexpected uncoupling of the Ras-extracellular signal-regulated kinase signaling cascade from the activated epidermal growth factor receptor. Mol. Cell Biol. 22, 5380-5394 DOI ScienceOn
30	Khachigian, L. M. and T. Collins. 1997. Inducible expression of Egr-1-dependent genes. A paradigm of transcriptional activation in vascular endothelium. Circ. Res. 81, 457-461 DOI ScienceOn
31	Korcheva, V., J. Wong, C. Corless, M. Iordanov, and B. Magun. 2005. Administration of ricin induces a severe inflammatory response via nonredundant stimulation of ERK, JNK, and P38 MAPK and provides a mouse model of hemolytic uremic syndrome. Am. J. Pathol. 166, 323-339 DOI ScienceOn
32	Azcona-Olivera, J. I., Y. Ouyang, J. Murtha, F. S. Chu, and J. J. Pestka. 1995. Induction of cytokine mRNAs in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): relationship to toxin distribution and protein synthesis inhibition. Toxicol. Appl. Pharmacol. 133, 109-120 DOI ScienceOn
33	Braddock, M. 2001. The transcription factor Egr-1: a potential drug in wound healing and tissue repair. Ann. Med. 33, 313-318 DOI ScienceOn
34	Bennett, R. L., W. L. Blalock, D. M. Abtahi, Y. Pan, S. A. Moyer, and W. S. May. 2006. RAX, the PKR activator, sensitizes cells to inflammatory cytokines, serum withdrawal, chemotherapy, and viral infection. Blood 108, 821-829 DOI ScienceOn
35	Bertolotti, A., X. Wang, I. Novoa, R. Jungreis, K. Schlessinger, J. H. Cho, A. B. West, and D. Ron. 2001 Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice. J. Clin. Invest. 107, 585-593 DOI ScienceOn
36	Bhat, R. V., S. R. Beedu, Y. Ramakrishna, and K. L. Munshi. 1989. Outbreak of trichothecene mycotoxicosis associated with consumption of mould-damaged wheat production in Kashmir Valley, India. Lancet 1, 35-37 DOI ScienceOn
37	Chung, Y. J., G. H. Yang, Z. Islam, and J. J. Pestka. 2003. Up-regulation of macrophage inflammatory protein-2 and complement 3A receptor by the trichothecenes deoxynivalenol and satratoxin G. Toxicology 186, 51-65 DOI ScienceOn
38	Dieckgraefe, B. K. and D. M. Weems. 1999. Epithelial injury induces egr-1 and fos expression by a pathway involving rotein kinase C and ERK. Am. J. Physiol. 276, G322-330
39	Fitzgerald, K. A. and L. A. O'Neill. 1999. Characterization of CD44 induction by IL-1: a critical role for Egr-1. J. Immunol. 162, 4920-4927
40	Ahmed, M. M., S. F. Sells, K. Venkatasubbarao, S. M. Fruitwala, S. Muthukkumar, C. Harp, M. Mohiuddin, and V. M. Rangnekar. 1997. Ionizing radiation-inducible apoptosis in the absence of p53 linked to transcription factor EGR-1. J. Biol. Chem. 272, 33056-33061 DOI ScienceOn