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Protective Role of Selenium in Immune-Relevant Cytokine and Immunoglobulin Production by Piglet Splenic Lymphocytes Exposed to Deoxynivalenol

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Abstract

Deoxynivalenol (DON) is a mycotoxin that causes immunosuppression, especially in swine. Selenium (Se) is essential for proper functioning of the immune system in animals. However, little is known about the effects of DON and Se on cytokine or immunoglobulin production in piglets. Here, we addressed this gap by examining piglet splenic lymphocyte responses in vitro. Cells were stimulated with concanavalin A, a T cell stimulatory lectin, in the absence or presence of DON (0.1, 0.2, 0.4, and 0.8 μg/mL), Se (Na2SeO3, 2 μM), or combinations of Se 2 μM and DON 0.1–0.8 μg/mL for 12, 24, or 48 h. At each time point, supernatants and cells were collected and the expression of cytokine and immunoglobulin protein and mRNA was examined. Compared with control and Se-alone treatments, DON exposure significantly and dose dependently decreased the expression levels of IL-2, IL-4, IL-6, IL-10, IFN-γ, IgG, and IgM mRNA and protein. By contrast, co-treatment with DON + Se significantly increased the mRNA and protein levels of all factors examined, except IL-4 and IL-6, compared with DON treatment alone. The results of this investigation demonstrate that Se has the potential to counteract DON-induced immunosuppression in piglets and is a promising treatment for DON-mediated toxicity.

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Abbreviations

DON:

Deoxynivalenol

Se:

Selenium

IL-2:

Interleukin-2

IFN-γ:

Interferon gamma

IgM:

Immunoglobulin M

ELISA:

Enzyme-linked immuneabsorbent assays

ConA:

Concanavalin A

References

  1. Ren, Z., Deng, H., Deng, Y. et al (2017) Combined effects of deoxynivalenol and zearalenone on oxidative injury and apoptosis in porcine splenic lymphocytes in vitro. Exp Toxicol Pathol

    Google Scholar 

  2. Desjardins AE (2007) Fusarium mycotoxins: chemistry, genetics, and biology. Plant Pathol 56(2):337–337

    Google Scholar 

  3. Rotter BA (1996) Invited review: toxicology of deoxynivalenol(vomitoxin). J Toxicol Environ Health 48(1):1–34

    Article  PubMed  CAS  Google Scholar 

  4. Pestka JJ, Smolinski AT (2005) Deoxynivalenol: toxicology and potential effects on humans. J Toxicol Environ Health Part B Crit Rev 8(1):39–69

    Article  CAS  Google Scholar 

  5. Liang Z, Ren Z, Gao S et al (2015) Individual and combined effects of deoxynivalenol and zearalenone on mouse kidney. Environ Toxicol Pharmacol 40(3):686

    Article  PubMed  CAS  Google Scholar 

  6. Ren ZH, Deng HD, Deng YT et al (2016) Effect of the Fusarium toxins, zearalenone and deoxynivalenol on the mouse brain. Environ Toxicol Pharmacol:46–62

  7. Ren Z, Wang Y, Deng H et al (2016) Effects of deoxynivalenol on calcium homeostasis of concanavalin A—stimulated splenic lymphocytes of chickens in vitro. Exp Toxicol Pathol 68(4):241–245

    Article  PubMed  CAS  Google Scholar 

  8. Mikami, O. (2011) Study on the effects of acute exposure to deoxynivalenol on the liver and immune system of pigs. Jap J Vet Res

  9. Zielonka L, Gajecki M, Obremski K et al (2003) Influence of low doses of deoxynivalenol applied per os on chosen indexes of immune response in swine. Pol J Vet Sci 6(3 suppl):74–77

    PubMed  CAS  Google Scholar 

  10. Goyarts T, Dänicke S, Tiemann U et al (2006) Effect of the Fusarium toxin deoxynivalenol (DON) on IgA, IgM and IgG concentrations and proliferation of porcine blood lymphocytes. Toxicol in Vitro 20(6):858–867

    Article  PubMed  CAS  Google Scholar 

  11. Marin, D. E., Taranu, I., Manda, G. et al (2006) In vitro effect of deoxynivalenol on porcine lymphocyte immune functions. Archiva Zootechnica

  12. Xue CY, Wang GH, Chen F et al (2010) Immunopathological effects of ochratoxin A and T-2 toxin combination on broilers. Poult Sci 89(6):1162–1166

    Article  PubMed  CAS  Google Scholar 

  13. Odhav B, Adam JK, Bhoola KD (2008) Modulating effects of fumonisin B1 and ochratoxin A on leukocytes and messenger cytokines of the human immune system. Int Immunopharmacol 8(6):799–809

    Article  PubMed  CAS  Google Scholar 

  14. Ouyang YL, Azcona-Olivera JI, Pestka JJ (1995) Effects of trichothecene structure on cytokine secretion and gene expression in murine CD4 + T-cells. Toxicology 104(1–3):187–202

    Article  PubMed  CAS  Google Scholar 

  15. Warner RL, Brooks K, Pestka JJ (1994) In vitro effects of vomitoxin (deoxynivalenol) on T-cell interleukin production and IgA secretion. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc 32(7):617–625

    Article  CAS  Google Scholar 

  16. Azcona-Olivera JI, Ouyang YL, Warner RL et al (1995) Effects of vomitoxin (deoxynivalenol) and cycloheximide on IL-2, 4, 5 and 6 secretion and mRNA levels in murine CD4 + cells. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc 33(6):433–441

    Article  CAS  Google Scholar 

  17. Reinhold U, Pawelec G, Enczmann J, Wernet P (1989) Class-specific effects of selenium on PWM-driven human antibody synthesis in vitro. Biol Trace Elem Res 20(1):45–58

    Article  PubMed  CAS  Google Scholar 

  18. Petrie HT, Klassen LW, Klassen PS et al (1989) Selenium and the immune response: 2. Enhancement of murine cytotoxic T-lymphocyte and natural killer cell cytotoxicity in vivo. J Leukoc Biol 45(3):215–220

    Article  PubMed  CAS  Google Scholar 

  19. Wang RD, Wang CS, Feng ZH et al (1992) Investigation on the effect of selenium on T lymphocyte proliferation and its mechanisms. J Tongji Med Univ 12(1):33–38

    Article  PubMed  Google Scholar 

  20. Xu D, Li W, Huang Y et al (2014) The effect of selenium and polysaccharide of Atractylodes macrocephala Koidz. (PAMK) on immune response in chicken spleen under heat stress. Biol Trace Elem Res 160(2):232

    Article  PubMed  CAS  Google Scholar 

  21. Wen ZS, Xu YL, Zou XT et al (2011) Chitosan nanoparticles act as an adjuvant to promote both Th1 and Th2 immune responses induced by ovalbumin in mice. Marine Drugs 9(6):1038–1055

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Qin S, Huang B, Ma J, Wang X et al (2015) Effects of selenium-chitosan on blood selenium concentration, antioxidation status, and cellular and humoral immunity in mice. Biol Trace Elem Res 165(2):145–152

    Article  PubMed  CAS  Google Scholar 

  23. Wang Y, Li J, Li Y et al (2016) Effect of different selenium supplementation levels on oxidative stress, cytokines, and immunotoxicity in chicken thymus. Biol Trace Elem Res 2:1–8

    CAS  Google Scholar 

  24. Hayek MG Jr, Harmon RJ et al (1989) Porcine immunoglobulin transfer after prepartum treatment with selenium or vitamin E. J Anim Sci 67(5):1299–1306

    Article  PubMed  CAS  Google Scholar 

  25. Khan MZ, Akter SH, Islam MN et al (2008) The effect of selenium and vitamin E on the lymphocytes and immunoglobulin-containing plasma cells in the lymphoid organ and mucosa-associated lymphatic tissues of broiler chickens. Anantomia Histologia Embryologia 37(1):52–59

    CAS  Google Scholar 

  26. Salimian J, Arefpour MA, Riazipour M et al (2014) Immunomodulatory effects of selenium and vitamin E on alterations in T lymphocyte subsets induced by T-2 toxin. Immunopharmacol Immunotoxicol 36(4):1–7

    Article  CAS  Google Scholar 

  27. Ahmadi A, Poursasan N, Amani J et al (2015) Adverse effect of T-2 toxin and the protective role of selenium and vitamin E on peripheral blood B lymphocytes. Iran J Immunol Iji 12(1):64–69

    PubMed  Google Scholar 

  28. Chen K, Yuan S, Chen J et al (2013) Effects of sodium selenite on the decreased percentage of T cell subsets, contents of serum IL-2 and IFN-γ induced by aflatoxin B 1 in broilers. Res Vet Sci 95(1):143–145

    Article  PubMed  CAS  Google Scholar 

  29. He Y, Fang J, Peng X et al (2014) Effects of sodium selenite on aflatoxin B1-induced decrease of ileac T cell and the mRNA contents of IL-2, IL-6, and TNF-α in broilers. Biol Trace Elem Res 159(1–3):167–173

    Article  PubMed  CAS  Google Scholar 

  30. Mubarak A, Rashid A, Khan IA et al (2009) Effect of vitamin E and selenium as immunomodulators on induced aflatoxicosis in broiler birds. Pak J Life Soc Sci 7:31–34

    Google Scholar 

  31. Ganter, M. (1995) Ketamine anesthesia in pig. Scand J Lab Anim Sci

  32. Zhuang T, Xu H, Hao S et al (2015) Effects of selenium on proliferation, interleukin-2 production and selenoprotein mRNA expression of normal and dexamethasone-treated porcine splenocyte. Res Vet Sci 98:59–65

    Article  PubMed  CAS  Google Scholar 

  33. Wang X, Zuo Z, Zhao C et al (2016) Protective role of selenium in the activities of antioxidant enzymes in piglet splenic lymphocytes exposed to deoxynivalenol. Environ Toxicol Pharmacol 47:53–61

    Article  PubMed  CAS  Google Scholar 

  34. Ren F, Chen X, Hesketh J et al (2012) Selenium promotes T-cell response to TCR-stimulation and ConA, but not PHA in primary porcine splenocytes. PLoS One 7(4):e35375

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Du X, Zhen S, Peng Z et al (2017) Acetoacetate induces hepatocytes apoptosis by the ROS-mediated MAPKs pathway in ketotic cows. Journal of Cellular Physiology

  36. Sun X, Yuan X, Chen L et al (2017) Histamine induces bovine rumen epithelial cell inflammatory response via NF-kappaB pathway. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology 42(3):1109–1119

    Article  CAS  Google Scholar 

  37. Pestka JJ (2008) Deoxynivalenol: toxicity, mechanisms and animal health risks. Anim Breed Feed 137(3):283–298

    Google Scholar 

  38. Pestka JJ (2008) Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Additives & Contaminants Part A Chemistry Analysis Control Exposure & Risk Assessment 25(9):1128–1140

    Article  CAS  Google Scholar 

  39. Pestka JJ, Smolinski AT (2005) Deoxynivalenol: toxicology and potential effects on humans. J Toxicol Environ Health Part B Crit Rev 8(1):39

    Article  CAS  Google Scholar 

  40. Zhou HR, Lau AS, Pestka JJ (2003) Role of double-stranded RNA-activated protein kinase R (PKR) in deoxynivalenol-induced ribotoxic stress response. Toxicol Sci 74(2):335

    Article  PubMed  CAS  Google Scholar 

  41. Awad WA, Ghareeb K, Böhm J, Zentek J (2010) Decontamination and detoxification strategies for the Fusarium mycotoxin deoxynivalenol in animal feed and the effectiveness of microbial biodegradation. Food Additives & Contaminants Part A Chemistry Analysis Control Exposure & Risk Assessment 27(4):510

    Article  CAS  Google Scholar 

  42. Yan G (2006) Detoxification of aflatoxins by the biological methods. China Feed

  43. Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383(6603):787–793

    Article  PubMed  CAS  Google Scholar 

  44. Meky FA, Hardie LJ, Evans SW et al (2001) Deoxynivalenol-induced immunomodulation of human lymphocyte proliferation and cytokine production. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc 39(9):827–836

    Article  CAS  Google Scholar 

  45. Xu F, Shuang L, Shu L (2015) Effects of selenium and cadmium on changes in the gene expression of immune cytokines in chicken splenic lymphocytes. Biol Trace Elem Res 165(2):214–221

    Article  PubMed  CAS  Google Scholar 

  46. Bonham M, O’Connor JM, Hannigan BM et al (2002) The immune system as a physiological indicator of marginal copper status? Br J Nutr 87(5):393

    Article  PubMed  CAS  Google Scholar 

  47. Malek TR, Bayer AL (2004) Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 4(9):665

    Article  PubMed  CAS  Google Scholar 

  48. Gajewski TF, Fitch FW (1988) Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol 140(12):4245–4252

    PubMed  CAS  Google Scholar 

  49. Szabo SJ, Jacobson NG et al (1995) Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 2(6):665

    Article  PubMed  CAS  Google Scholar 

  50. Goodbourn S, Didcock L, Randall RE, Goodbourn S, Didcock L, Randall RE (2000) Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol 81(10):2341–2364

    Article  PubMed  CAS  Google Scholar 

  51. Azconaolivera JI, Ouyang Y, Murtha J et al (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(1):109–120

    Article  CAS  Google Scholar 

  52. Zhou HR, Yan D, Pestka JJ (1997) Differential cytokine mRNA expression in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): dose response and time course. Toxicol Appl Pharmacol 144(2):294–305

    Article  PubMed  CAS  Google Scholar 

  53. Van LTB, Lemay M, Bastien A et al (2016) The potential effects of antioxidant feed additives in mitigating the adverse effects of corn naturally contaminated with Fusarium mycotoxins on antioxidant systems in the intestinal mucosa, plasma, and liver in weaned pigs. Mycotoxin Res 32(2):1–18

    Google Scholar 

  54. Cohen MC, Cohen S (1996) Cytokine function: a study in biologic diversity. Am J Clin Pathol 105(5):589

    Article  PubMed  CAS  Google Scholar 

  55. Ouyang YL, Azcona-Olivera JI, Pestka JJ (1995) Effects of trichothecene structure on cytokine secretion and gene expression in murine CD4 + T-cells. Toxicology 104(1–3):187

    Article  PubMed  CAS  Google Scholar 

  56. Dong WM, Azconaolivera JI, Brooks KH et al (1994) Elevated gene expression and production of interleukins 2, 4, 5, and 6 during exposure to vomitoxin (deoxynivalenol) and cycloheximide in the EL-4 thymoma. Toxicol Appl Pharmacol 127(2):282–290

    Article  PubMed  CAS  Google Scholar 

  57. Wong SS, Schwartz RC, Pestka JJ (2001) Superinduction of TNF-α and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization. Toxicology 161(1–2):139–149

    Article  PubMed  CAS  Google Scholar 

  58. Ren Z, Wang Y, Deng H et al (2015) Deoxynivalenol-induced cytokines and related genes in concanavalin A-stimulated primary chicken splenic lymphocytes. Toxicol In Vitro: Int J Publ Assoc BIBRA 29(3):558–563

    Article  CAS  Google Scholar 

  59. Chen K, Shu G, Peng X et al (2013) Protective role of sodium selenite on histopathological lesions, decreased T-cell subsets and increased apoptosis of thymus in broilers intoxicated with aflatoxin B 1. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc 59(3):446–454

    CAS  Google Scholar 

  60. Yu Z, Wang F, Liang N et al (2015) Effect of selenium supplementation on apoptosis and cell cycle blockage of renal cells in broilers fed a diet containing aflatoxin B 1. Biol Trace Elem Res 168(1):242–251

    Article  PubMed  CAS  Google Scholar 

  61. Song Y, Li N, Gu J et al (2016) β-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway. J Dairy Sci 99(11):9184

    Article  PubMed  CAS  Google Scholar 

  62. Ren Z, Wang Y, Deng H et al (2015) Deoxynivalenol induces apoptosis in chicken splenic lymphocytes via the reactive oxygen species-mediated mitochondrial pathway. Environ Toxicol Pharmacol 39(1):339

    Article  PubMed  CAS  Google Scholar 

  63. Mishra S, Dwivedi PD, Pandey HP et al (2014) Role of oxidative stress in Deoxynivalenol induced toxicity. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc 72(3):20–29

    Article  CAS  Google Scholar 

  64. Tapiero H, Townsend DM, Tew KD (2003) The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother 57(3–4):134–144

    Article  PubMed  CAS  Google Scholar 

  65. Matés JM (2000) Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153(1–3):83–104

    Article  PubMed  Google Scholar 

  66. Maquat LE (2001) Evidence that selenium deficiency results in the cytoplasmic decay of GPx1 mRNA dependent on pre-mRNA splicing proteins bound to the mRNA exon-exon junction. Biofactors 14(1–4):37–42

    Article  PubMed  CAS  Google Scholar 

  67. Vitetta ES, Brooks K, Chen YW et al (1984) T cell-derived lymphokines that induce IgM and IgG secretion in activated murine B cells. Immunol Rev 78(1):137

    Article  PubMed  CAS  Google Scholar 

  68. Bryant A, Calver NC, Toubi E et al (1990) Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2. Clin Immunol Immunopathol 56(2):239

    Article  PubMed  CAS  Google Scholar 

  69. Warner RL, Brooks K, Pestka JJ (1994) In vitro effects of vomitoxin (deoxynivalenol) on T-cell interleukin production and IgA secretion. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc 32(7):617

    Article  CAS  Google Scholar 

  70. Ren ZH, Zhou R, Deng JL et al (2014) Effects of the Fusarium toxin zearalenone (ZEA) and/or deoxynivalenol (DON) on the serum IgA, IgG and IgM levels in mice. Food Agric Immunol 25(4):600–606

    Article  CAS  Google Scholar 

  71. Mckenzie RC, Rafferty TS, Beckett GJ (1998) Selenium: an essential element for immune function. Immunol Today 19(8):342–345

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Anne M. O’Rourke, PhD, from Liwen Bianji, Edanz Group China (www. Liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Funding

The present work was supported by the National Natural Science Fund of China (31402269) and the Changjiang Scholars and Innovative Research Team of Ministry of Education of China Funds (grant no. IRTO848).

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Author notes

  1. X. M. Wang, Z. C. Zuo, and J. L. Deng contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. College of Veterinary Medicine, Sichuan Province Key Laboratory of Animal Disease and Human Health, Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China

    Xuemei Wang, Zhicai Zuo, Junliang Deng, Zhuo Zhang, Changhao Chen, Yu Fan, Guangneng Peng, Suizhong Cao, Yanchun Hu, Shumin Yu & Zhihua Ren

  2. College of Life Science and Technology, Southwest University for Nationalities, Chengdu, Sichuan, 610041, China

    Chaoxi Chen

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  1. Xuemei Wang
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Correspondence to Zhihua Ren.

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Wang, X., Zuo, Z., Deng, J. et al. Protective Role of Selenium in Immune-Relevant Cytokine and Immunoglobulin Production by Piglet Splenic Lymphocytes Exposed to Deoxynivalenol. Biol Trace Elem Res 184, 83–91 (2018). https://doi.org/10.1007/s12011-017-1160-6

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