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Protective Effect of Saccharomyces boulardii on Deoxynivalenol-Induced Injury of Porcine Macrophage via Attenuating p38 MAPK Signal Pathway

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Abstract

The aims of our study were to evaluate the effects of Saccharomyces boulardii (S. boulardii) on deoxynivalenol (DON)-induced injury in porcine alveolar macrophage cells (PAMCs) and to explore the underlying mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, ELISA, qRT-PCR, and western blot were performed to assess whether S. boulardii could prevent DON-induced injury by p38 mitogen-activated protein kinase (p38 MAPK) signal pathway. The results showed that pretreatment with 8 μM DON could decrease the viability of PAMC and significantly increase the apoptosis rate of PAMC, whereas S. boulardii could rescue apoptotic PAMC cells induced by DON. Further experiments revealed that S. boulardii effectively reversed DON-induced cytotoxicity via downregulating the expression of TNF-α, IL-6, and IL-lβ. In addition, S. boulardii significantly alleviated DON-induced phosphorylation and mRNA expression of p38 and further increased the expression of apoptosis regulation genes Bcl-xl and Bcl-2 and inhibited the activation of Bax. Our results suggest that S. boulardii could suppress DON-induced p38 MAPK pathway activation and reduce the expression of downstream inflammatory cytokines, as well as promote the expression of anti-apoptotic genes to inhibit apoptosis induced by DON in PAMC.

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References

  1. Helle, H., Nielsen, K. F., Ulf, T., & Susanne, E. (2002). Production of trichothecenes and other secondary metabolites by Fusarium culmorum and Fusarium equiseti on common laboratory media and a soil organic matter agar: an ecological interpretation. Journal of Agricultural & Food Chemistry, 50, 7593–7599.

    Article  Google Scholar 

  2. Tralamazza, S. M., Bemvenuti, R. H., Zorzete, P., de Souza Garcia, F., & Correa, B. (2016). Fungal diversity and natural occurrence of deoxynivalenol and zearalenone in freshly harvested wheat grains from Brazil. Food Chemistry, 196, 445–450.

    Article  CAS  Google Scholar 

  3. Goossens, J., Pasmans, F., Verbrugghe, E., Vandenbroucke, V., Baere, S. D., Meyer, E., Haesebrouck, F., Backer, P. D., & Croubels, S. (2012). Porcine intestinal epithelial barrier disruption by the Fusarium mycotoxins deoxynivalenol and T-2 toxin promotes transepithelial passage of doxycycline and paromomycin. BMC Veterinary Research, 8, 620–620.

    Article  Google Scholar 

  4. Pestka, J. J., & Smolinski, A. T. (2005). Deoxynivalenol: toxicology and potential effects on humans. Journal of Toxicology & Environmental Health Part B Critical Reviews, 8, 39–69.

    Article  CAS  Google Scholar 

  5. Pestka, J. J. (2010). Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Archives of Toxicology, 84, 663–679.

    Article  CAS  Google Scholar 

  6. Mcmullen, M., Jones, R., & Gallenberg, D. (1997). Scab of wheat and barley: a re-emerging disease of devastating impact. Plant Disease, 81, 1340–1348.

    Article  Google Scholar 

  7. Li, M., Harkema, J., Cuff, C. F., & Pestka, J. (2007). Deoxynivalenol exacerbates viral bronchopneumonia induced by respiratory reovirus infection. Toxicological Sciences An Official Journal of the Society of Toxicology, 95, 412–426.

    Article  CAS  Google Scholar 

  8. Pestka, J. J., Hui-Ren, Z., Moon, Y., & Chung, Y. J. (2004). Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicology Letters, 153, 61–73.

    Article  CAS  Google Scholar 

  9. Turner, P. C., Burley, V. J., Rothwell, J. A., White, K. L. M., Cade, J. E., & Wild, C. P. (2008). Dietary wheat reduction decreases the level of urinary deoxynivalenol in UK adults. Journal of Exposure Science & Environmental Epidemiology, 18, 392–399.

    Article  CAS  Google Scholar 

  10. Bondy, G. S., & Pestka, J. J. (2000). Immunomodulation by fungal toxins. Journal of Toxicology & Environmental Health Part B Critical Reviews, 3, 109–143.

    Article  CAS  Google Scholar 

  11. Sugita-Konishi, Y., & Pestka, J. J. (2001). Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model. Journal of Toxicology & Environmental Health Part A, 64, 619–636.

    Article  CAS  Google Scholar 

  12. Liu, Y., & Schubert, D. (1997). Cytotoxic amyloid peptides inhibit cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction by enhancing MTT formazan exocytosis. Journal of Neurochemistry, 69, 2285–2293.

    Article  CAS  Google Scholar 

  13. Laskin, J. D., Heck, D. E., & Laskin, D. L. (2002). The ribotoxic stress response as a potential mechanism for MAP kinase activation in xenobiotic toxicity. Toxicological Sciences An Official Journal of the Society of Toxicology, 69, 289–291.

    Article  CAS  Google Scholar 

  14. Grethe, S., Ares, M. P. S., Andersson, T., Pörn-Aress, & Isabella, M. (2004). p38 MAPK mediates TNF-induced apoptosis in endothelial cells via phosphorylation and downregulation of Bcl-x(L). Experimental Cell Research, 298, 632–642.

    Article  CAS  Google Scholar 

  15. Jiménez, B., Volpert, O. V., Crawford, S. E., Febbraio, M., Silverstein, R. L., & Bouck, N. (2000). Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nature Medicine, 6, 41–48.

    Article  Google Scholar 

  16. Nakagami, H., Morishita, R., Yamamoto, K., Yoshimura, S. I., Taniyama, Y., Aoki, M., Matsubara, H., Kim, S., Kaneda, Y., & Ogihara, T. (2001). Phosphorylation of p38 mitogen-activated protein kinase downstream of Bax-caspase-3 pathway leads to cell death induced by high D-glucose in human endothelial cells. Diabetes, 50, 1472–1481.

    Article  CAS  Google Scholar 

  17. Zhou, H. R., Islam, Z., & Pestka, J. J. (2005). Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol. Toxicological Sciences, 87, 113–122.

    Article  CAS  Google Scholar 

  18. Abdel-Wahhab, M. A., El-Kady, A. A., Hassan, A. M., Abd El-Moneim, O. M., & Abdel-Aziem, S. H. (2015). Effectiveness of activated carbon and Egyptian montmorillonite in the protection against deoxynivalenol-induced cytotoxicity and genotoxicity in rats. Food and Chemical Toxicology, 83, 174–182.

    Article  CAS  Google Scholar 

  19. Wu, L., Liao, P., He, L., Feng, Z., Ren, W., Yin, J., Duan, J., Li, T., & Yin, Y. (2015). Dietary L-arginine supplementation protects weanling pigs from deoxynivalenol-induced toxicity. Toxins, 7, 1341–1354.

    Article  CAS  Google Scholar 

  20. Li, W., Wence, W., Kang, Y., Ting, Z., Jie, Y., Tiejun, L., Lin, Y., Liuqin, H., Xiaojian, Y., & Hongfu, Z. (2013). Effects of dietary arginine and glutamine on alleviating the impairment induced by deoxynivalenol stress and immune relevant cytokines in growing pigs. PloS One, 8, e69502–e69502.

    Article  Google Scholar 

  21. Weaver, A. C., Todd See, M., Hansen, J. A., Kim, Y. B., De Souza, A. L. P., Middleton, T. F., & Kim, S. W. (2013). The use of feed additives to reduce the effects of aflatoxin and deoxynivalenol on pig growth, organ health and immune status during chronic exposure. Toxins, 5, 1261–1281.

    Article  CAS  Google Scholar 

  22. Milne, A. (2008). Summary of ‘probiotics for the prevention of pediatric antibiotic-associated diarrhea’. Evidence-Based Child Health: A Cochrane Review Journal, 3, 316–317.

    Article  Google Scholar 

  23. Guslandi, M. (2015). Role of probiotics in Crohn’s disease and in pouchitis. Journal of Clinical Gastroenterology, 49(Suppl 1), 46–49.

    Article  Google Scholar 

  24. Oelschlaeger, T. A. (2010). Mechanisms of probiotic actions—a review. International Journal of Medical Microbiology, 300, 57–62.

    Article  CAS  Google Scholar 

  25. Pontier-Bres, R., Rampal, P., Peyron, J. F., Munro, P., Lemichez, E., & Czerucka, D. (2015). The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin. Toxins, 7, 4455–4467.

    Article  CAS  Google Scholar 

  26. Agawane, S. (2004). Original articles: effect of probiotic containing Saccharomyces boulardii on experimental ochratoxicosis in broilers: hematobiochemical studies. Journal of Veterinary Science, 5, 359–367.

    CAS  Google Scholar 

  27. Chen, X., Kokkotou, E., Mustafa, N., Bhaskar, K., Sougioultzis, S., O’Brien, M., Pothoulakis, C., & Kelly, C. (2006). Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against Clostridium difficile toxin A-induced enteritis. Journal of Biological Chemistry, 281, 24449–24454.

    Article  CAS  Google Scholar 

  28. Shetty, P. H., & Jespersen, L. (2006). Saccharomyces cerevisiae and lactic acid bacteria as potential mycotoxin decontaminating agents. Trends in Food Science & Technology, 17, 48–55.

    Article  CAS  Google Scholar 

  29. Da, S. J., Peluzio, J. M., Prado, G., Madeira, J. E., Silva, M. O., de Morais, P. B., Rosa, C. A., Pimenta, R. S., & Nicoli, J. R. (2015). Use of probiotics to control aflatoxin production in peanut grains. Scientific World Journal, 2015, 1–8.

    Google Scholar 

  30. Xia, Z., Li, Z., Zhang, M., Sun, L., Zhang, Q., & Qiu, X. (2016). CARMA3 regulates the invasion, migration, and apoptosis of non-small cell lung cancer cells by activating NF-кB and suppressing the P38 MAPK signaling pathway. Experimental and Molecular Pathology, 100, 353–360.

    Article  CAS  Google Scholar 

  31. Kim, D. H., Kim, M. E., & Lee, J. S. (2015). Inhibitory effects of extract from G. lanceolata on LPS-induced production of nitric oxide and IL-1β via down-regulation of MAPK in macrophages. Applied Biochemistry and Biotechnology, 175, 657–665.

    Article  CAS  Google Scholar 

  32. Li, C., Wang, T., Zhang, C., Xuan, J., Su, C., & Wang, Y. (2016). Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways. Gene, 577, 275–280.

    Article  CAS  Google Scholar 

  33. Islam, M. R., Roh, Y. S., Kim, J., Lim, C. W., & Kim, B. (2013). Differential immune modulation by deoxynivalenol (vomitoxin) in mice. Toxicology Letters, 221, 152–163.

    Article  CAS  Google Scholar 

  34. Marsden, V. S., & Strasser, A. (2003). Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more. Annual Review of Immunology, 21, 71–105.

    Article  CAS  Google Scholar 

  35. Capasso, L., Longhin, E., Caloni, F., Camatini, M., & Gualtieri, M. (2015). Synergistic inflammatory effect of PM10 with mycotoxin deoxynivalenol on human lung epithelial cells. Toxicon: official journal of the International Society on Toxinology, 104, 65–72.

    Article  CAS  Google Scholar 

  36. Goyarts, T., Dänicke, S., Tiemann, U., & Rothkötter, H. J. (2006). Effect of the Fusarium toxin deoxynivalenol (DON) on IgA, IgM and IgG concentrations and proliferation of porcine blood lymphocytes. Toxicology In Vitro, 20, 858–867.

    Article  CAS  Google Scholar 

  37. Goyarts, T., Grove, N., & Dänicke, S. (2006). Effects of the Fusarium toxin deoxynivalenol from naturally contaminated wheat given subchronically or as one single dose on the in vivo protein synthesis of peripheral blood lymphocytes and plasma proteins in the pig. Food & Chemical Toxicology, 44, 1953–1965.

    Article  CAS  Google Scholar 

  38. Susanne Döll, J. A. S., Dänicke, S., & Fink-Gremmels, J. (2009). Deoxynivalenol-induced cytotoxicity, cytokines and related genes in unstimulated or lipopolysaccharide stimulated primary porcine macrophages. Toxicology Letters, 184, 97–106.

    Article  Google Scholar 

  39. Boeira, L., Bryce, J., Stewart, G., & Flannigan, B. (2000). The effect of combinations of Fusarium mycotoxins (deoxynivalenol, zearalenone and fumonisin B1) on growth of brewing yeasts. Journal of Applied Microbiology, 88, 388–403.

    Article  CAS  Google Scholar 

  40. Kutuk, O., & Basaga, H. (2006). Bcl-2 protein family: implications in vascular apoptosis and atherosclerosis. Apoptosis, 11, 1661–1675.

    Article  CAS  Google Scholar 

  41. An, J., Gao, Y., Wang, J., Zhu, Q., Ma, Y., Wu, J., Sun, J., & Tang, Y. (2012). Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathway. Biotechnology Letters, 34, 1781–1788.

    Article  CAS  Google Scholar 

  42. Korsmeyer, S. J. (1995). Regulators of cell death. Trends in Genetics Tig, 11, 101–105.

    Article  CAS  Google Scholar 

  43. Iwahashi, H., Eguchi, Y., Yasuhara, N., Hanafusa, T., Matsuzawa, Y., & Tsujimoto, Y. (1997). Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy. Nature, 390, 413–417.

    Article  CAS  Google Scholar 

  44. Song, W., Yang, H.-B., Chen, P., Wang, S.-M., Zhao, L.-P., Xu, W.-H., Fan, H.-F., Gu, X., & Chen, L.-Y. (2013). Apoptosis of human gastric carcinoma SGC-7901 induced by deoxycholic acid via the mitochondrial-dependent pathway. Applied Biochemistry and Biotechnology, 171, 1061–1071.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  46. Wong, S. S., Schwartz, R. C., & Pestka, J. J. (2001). Superinduction of TNF-α and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization. Toxicology, 161, 139–149.

    Article  CAS  Google Scholar 

  47. Wong, S. S., Zhou, H. R., Marin-Martinez, M. L., Brooks, K., & Pestka, J. J. (1998). Modulation of IL-1beta, IL-6 and TNF-alpha secretion and mRNA expression by the trichothecene vomitoxin in the RAW 264.7 murine macrophage cell line. Food & Chemical Toxicology, 36, 409–419.

    Article  CAS  Google Scholar 

  48. Badia, R., Zanello, G., Chevaleyre, C., Lizardo, R., Meurens, F., Martínez, P., Brufau, J., & Salmon, H. (2012). Effect of Saccharomyces cerevisiae var. Boulardii and β-galactomannan oligosaccharide on porcine intestinal epithelial and dendritic cells challenged in vitro with Escherichia coli F4 (K88). Veterinary Research, 43, 1–11.

    Article  Google Scholar 

  49. Zanello, G., Berri, M., Dupont, J., Sizaret, P. Y., D’Inca, R., Salmon, H., & Meurens, F. (2011). Saccharomyces cerevisiae modulates immune gene expressions and inhibits ETEC-mediated ERK1/2 and p38 signaling pathways in intestinal epithelial cells. PloS One, 6, e18573.

    Article  CAS  Google Scholar 

  50. Thomas, S., Przesdzing, I., Metzke, D., Schmitz, J., Radbruch, A., & Baumgart, D. C. (2009). Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation. Clinical & Experimental Immunology, 156, 78–87.

    Article  CAS  Google Scholar 

  51. Liu, Z., Zhang, Q., Peng, H., & Zhang, W.-Z. (2012). Animal lectins: potential antitumor therapeutic targets in apoptosis. Applied Biochemistry and Biotechnology, 168, 629–637.

    Article  CAS  Google Scholar 

  52. Yang, G. H., Jarvis, B. B., Chung, Y. J., & Pestka, J. J. (2000). Apoptosis induction by the satratoxins and other trichothecene mycotoxins: relationship to ERK, p38 MAPK, and SAPK/JNK activation. Toxicology & Applied Pharmacology, 164, 149–160.

    Article  CAS  Google Scholar 

  53. Yong-Joo, C., Hui-Ren, Z., & Pestka, J. J. (2003). Transcriptional and posttranscriptional roles for p38 mitogen-activated protein kinase in upregulation of TNF-alpha expression by deoxynivalenol (vomitoxin). Toxicology & Applied Pharmacology, 193, 188–201.

    Article  Google Scholar 

  54. Smith, S. J., Fenwick, P. S., Nicholson, A. G., Kirschenbaum, F., Finney-Hayward, T. K., Higgins, L. S., Giembycz, M. A., Barnes, P. J., & Donnelly, L. E. (2006). Inhibitory effect of p38 mitogen-activated protein kinase inhibitors on cytokine release from human macrophages. British Journal of Pharmacology, 149, 393–404.

    Article  CAS  Google Scholar 

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The authors acknowledge the financial support from the National Natural Science Foundation of China (31302139).

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Correspondence to Jin-E Wu.

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Chang, C., Wang, K., Zhou, SN. et al. Protective Effect of Saccharomyces boulardii on Deoxynivalenol-Induced Injury of Porcine Macrophage via Attenuating p38 MAPK Signal Pathway. Appl Biochem Biotechnol 182, 411–427 (2017). https://doi.org/10.1007/s12010-016-2335-x

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