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Effects of deoxynivalenol- and zearalenone-contaminated feed on the gene expression profiles in the kidneys of piglets

  • Reddy, Kondreddy Eswar (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Lee, Woong (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Jeong, Jin young (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Lee, Yookyung (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Lee, Hyun-Jeong (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Kim, Min Seok (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Kim, Dong-Woon (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Yu, Dongjo (Swine Science Division, National Institute of Animal Science, RDA) ;
  • Cho, Ara (Animal Disease and Biosecurity Team, National Institute of Animal Science, RDA) ;
  • Oh, Young Kyoon (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA) ;
  • Lee, Sung Dae (Animal Nutritional and Physiology Team, National Institute of Animal Science, RDA)
  • Received : 2017.06.13
  • Accepted : 2017.08.31
  • Published : 2018.01.01

Abstract

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

Keywords

References

  1. Shephard GS, Thiel PG, Stockenstrom S, Sydenham EW. Worldwide survey of fumonisin contamination of corn and corn-based products. J AOAC Int 1996;79:671-87.
  2. Doll S, Danicke S. The Fusarium toxins deoxynivalenol (DON) and zearalenone (ZEN) in animal feeding. Prev Vet Med 2011;102:132-45. https://doi.org/10.1016/j.prevetmed.2011.04.008
  3. Cano PM, Seeboth J, Meurens F, et al. Deoxynivalenol as a new factor in the persistence of intestinal inflammatory diseases: an emerging hypothesis through possible modulation of Th17- mediated response. PLoS One 2013;8:e53647. https://doi.org/10.1371/journal.pone.0053647
  4. Rotter BA, Prelusky DB, Pestka JJ. Toxicology of deoxynivalenol (vomitoxin). J Toxicol Environ Health 1996;48:1-34.
  5. Rotter BA, Thompson BK, Clarkin S, Owen TC. Rapid colorimetric bioassay for screening of fusarium mycotoxins. Nat Toxins 1993;1: 303-7. https://doi.org/10.1002/nt.2620010509
  6. Pestka JJ, Zhou HR, Moon Y, et al. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicol Lett 2004;53:61-73.
  7. Diekman MA, Green ML. Mycotoxins and reproduction in domestic livestock. J Anim Sci 1992;70:1615-27. https://doi.org/10.2527/1992.7051615x
  8. Takemura H, Shim JY, Sayama K, et al. Characterization of the estrogenic activities of zearalenone and zeranol in vivo and in vitro. J Steroid Biochem Mol Biol 2007;103:170-7. https://doi.org/10.1016/j.jsbmb.2006.08.008
  9. Koraichi F, Videmann B, Mazallon M, et al. Zearalenone exposure modulates the expression of ABC transporters and nuclear receptors in pregnant rats and fetal liver. Toxicol Lett 2012;211:246-56. https://doi.org/10.1016/j.toxlet.2012.04.001
  10. Ghedira-Chekir L, Maaroufi K, Creppy EE, Bacha H. Cytotoxic and genotoxic effects of zearalenone: prevention by vitamin E. J Toxicol Toxin Rev 1999;18:355-68.
  11. National Research Council (NRC). Nutrition requirements of swine. 11th edition. Washington, DC, USA: National Academy Press; 2012.
  12. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010;26:139-40. https://doi.org/10.1093/bioinformatics/btp616
  13. Reddy KE, Jeong JY, Lee SD, et al. Effect of different early weaning regimens for calves on adipogenic gene expression in Hanwoo loin at the fattening stage. Livest Sci 2017;195:87-98. https://doi.org/10.1016/j.livsci.2016.11.014
  14. Dennis G, Jr, Sherman BT, Hosack DA, et al. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 2003;4:R60.
  15. Block SM. Kinesin: what gives? Cell 1998;93:5-8.
  16. Do KN, Fink LN, Jensen TE, Gautier L, Parlesak A. TLR2 controls intestinal carcinogen detoxication by CYP1A1. PloS One 2012;7:e32309. https://doi.org/10.1371/journal.pone.0032309
  17. Tomlinson IM, Cook GP, Walter G, et al. A complete map of the human immunoglobulin VH locus. Ann NY Acad Sci 1995;764:43-6.
  18. Butler JE, Wertz N. Antibody repertoire development in fetal and neonatal piglets. XVII. IgG subclass transcription revisited with emphasis on new IgG3. J Immunol 2006;177:5480-9. https://doi.org/10.4049/jimmunol.177.8.5480
  19. Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides 2003;24:523-30. https://doi.org/10.1016/S0196-9781(03)00114-1
  20. Cheng AL, Huang WG, Chen ZC, et al. Identification of novel nasopharyngeal carcinoma biomarkers by laser capture microdissection and proteomic analysis. Clin Cancer Res 2008;14:435-45. https://doi.org/10.1158/1078-0432.CCR-07-1215
  21. Hikami K, Ehara Y, Hasegawa M, et al. Association of IL-10 receptor 2 (IL10RB) SNP with systemic sclerosis. Biochem Biophys Res Commun 2008;373:403-7. https://doi.org/10.1016/j.bbrc.2008.06.054
  22. Pistol GC, Gras MA, Marin DE, et al. Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-kappaB signalling molecules in pigs. Br J Nutr 2014;111:452-64. https://doi.org/10.1017/S0007114513002675
  23. Dufour JH, Dziejman M, Liu MT, et al. IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 2002;168:3195-204. https://doi.org/10.4049/jimmunol.168.7.3195
  24. Altara R, Manca M, Hessel MH, et al. CXCL10 is a circulating inflammatory marker in patients with advanced heart failure: a pilot study. J Cardiovasc Transl 2016;9:302-14. https://doi.org/10.1007/s12265-016-9703-3
  25. Johannes FW, Martani JL, Lissinda HD, Lizelle Z. Evaluation of the cytotoxic properties, gene expression profiles and secondary signalling responses of cultured cells exposed to fumonisin B1, deoxynivalenol and zearalenone mycotoxins. Arch Toxicol 2016;91:2265-82.
  26. Shen Q, Singh P. Identification of a novel SP3 binding site in the promoter of human IGFBP4 gene: role of SP3 and AP-1 in regulating promoter activity in CaCo2 cells. Oncogene 2004;23:2454-64. https://doi.org/10.1038/sj.onc.1207354
  27. Wan D, Wang X, Wu Q, et al. Integrated transcriptional and proteomic analysis of growth hormone suppression mediated by trichothecene T-2 toxin in rat GH3 cells. Toxicol Sci 2015;147:326. https://doi.org/10.1093/toxsci/kfv131
  28. Kalaria RN, Kroon SN. Complement inhibitor C4-binding protein in amyloid deposits containing serum amyloid P in Alzheimer's disease. Biochem Biophys Res Commun 1992;186:461-6. https://doi.org/10.1016/S0006-291X(05)80830-7
  29. Kaplan R, Morse B, Huebner K, et al. Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked proteintyrosine-phosphatases expressed in brain. Proc Natl Acad Sci USA 1990; 87:7000-4. https://doi.org/10.1073/pnas.87.18.7000
  30. Goyarts T, Danicke S, Tiemann U, Rothkotter HJ. Effect of the Fusarium toxin deoxynivalenol (DON) on IgA, IgM and IgG concentrations and proliferation of porcine blood lymphocytes. Toxicol In Vitro 2006;20;858-67. https://doi.org/10.1016/j.tiv.2005.12.006
  31. Li M, Harkema JR, Cuff CF, Pestka JM. Deoxynivalenol exacerbates viral Bronchopneumonia induced by respiratory reovirus infection. Toxicol Sci 2007;95:412-26.
  32. Kim SH, Park YY, Kim SW, et al. ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression. Cancer Res 2011;71:7010-20. https://doi.org/10.1158/0008-5472.CAN-11-1262
  33. Amuzie, CJ, Shinozuka J, Pestka JJ. Induction of suppressors of cytokine signaling by the trichothecene deoxynivalenol in the mouse. Toxicol Sci 2009;111:277-87. https://doi.org/10.1093/toxsci/kfp150
  34. Croker BA, Kiu H, Nicholson SE. SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 2008;19:414-22.
  35. Wu Q, Dohnal V, Huang L, Kuca K, Yuan Z. Metabolic pathways of trichothecenes. Drug Metab Rev 2010;42:250-67. https://doi.org/10.3109/03602530903125807
  36. Gu MJ, Song SK, Lee IK, et al. Barrier protection via Toll-like receptor 2 signaling in porcine intestinal epithelial cells damaged by deoxynivalnol. Vet Res 2016;47:25.
  37. Pistol GC, Braicu C, Motiu M, et al. Zearalenone mycotoxin affects immune mediators, MAPK Signalling molecules, nuclear receptors and genome-wide gene expression in pig spleen. PLoS ONE 2015; 10:e0127503. https://doi.org/10.1371/journal.pone.0127503
  38. Hueza IM, Tanabe VK, Benassi JC, Raspantini LER, Gorniak SL. Zearalenone: An estogenic mycotoxin with immunotoxic effects. 8th International Symposium on Poisonous Plants; 2009 May; Paraiba, Brazil.
  39. Bolognesi C. Genotoxicity of pesticides: A review of human biomonitoring studies. Mutat Res 2003;543:251-72. https://doi.org/10.1016/S1383-5742(03)00015-2
  40. Zhang ZQ, Wang SB, Wang RG, et al. Phosphoproteome analysis reveals the molecular mechanisms underlying deoxynivalenolinduced intestinal toxicity in IPEC-J2 cells. Toxins 2016;8:270. https://doi.org/10.3390/toxins8100270
  41. Liang Z, Ren Z, Gao S, et al. Individual and combined effects of deoxynivalenol and zearalenone on mouse kidney. Environ Toxicol Pharmacol 2015;40:686-91. https://doi.org/10.1016/j.etap.2015.08.029
  42. Stoeker L, Nordone S, Gunderson S, et al. Assessment of Lactobacillus gasseri as a candidate oral vaccine vector. Clin Vaccine Immunol 2011;18:1834-44. https://doi.org/10.1128/CVI.05277-11
  43. Becker C, Reiter M, Pfaffl MW, et al. Expression of immune relevant genes in pigs under the influence of low doses of deoxynivalenol (DON). Mycotoxin Res 2011;27:287-93.
  44. CCFAC. Codex Committee on Food Additives and Contaminants. Posting date. Joint FAO/WHO Expert Committee on Food Additives: Position paper on zearalenone. Publication CCFAC 00/19. Rome, Italy: Codex Alimentarius Commission; 2000.
  45. Tiemann U, Brussow KP, Jonas L, et al. Effects of diets with cereal grains contaminated by graded levels of two Fusarium toxins on selected immunological and histological parameters of spleen in gilts. J Anim Sci 2006;84:236-45. https://doi.org/10.2527/2006.841236x
  46. Kouadio JH, Mobio TA, Baudrimont I, et al. Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2. Toxicology 2005;213:56-65. https://doi.org/10.1016/j.tox.2005.05.010
  47. Jung HC, Eckmann L, Yang SK, et al. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 1995;95:55-65.
  48. Pestka JJ, Amuzie CJ. Tissue distribution and proinflammatory cytokine gene expression following acute oral exposure to deoxynivalenol: comparison of weanling and adult mice. Food Chem Toxicol 2008;46: 2826-31. https://doi.org/10.1016/j.fct.2008.05.016
  49. Alizadeh A, Braber S, Akbari P, Garssen J, Gremmels JF. Deoxynivalenol impairs weight gain and affects markers of gut health after low-dose, short-term exposure of growing pigs. Toxins 2015;7:2071-95. https://doi.org/10.3390/toxins7062071

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