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Exposure to Penicillium mycotoxins alters gene expression of enzymes involved in the epigenetic regulation of bovine macrophages (BoMacs)

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Abstract

In this study, the modulation of key enzymes involved in epigenetic regulation was assessed in immortalized bovine macrophages (BoMacs) following in vitro exposure to the following Penicillium mycotoxins: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA), penicillic acid (PA), or a combination of one of the above with OTA at the concentration that inhibits BoMac proliferation by 25 % (IC25). Real-time PCR analysis of the genes coding DNA methyltransferases (DNMTs), histone demethylases (JMJD-3 and UTX), as well as the class-1 histone deacetylases (HDAC−1, −2, and −3) and histone acetylase (Bmi-1) was assessed following 6 h of mycotoxin exposure. A change in the expression of JMJD-3 as well as HDAC-3, MPA (p = 0.1) and PA (p = 0.08), by at least one of the treatments was observed at their respective IC25. The expression of JMJD-3 was significantly induced by PA, but synergistically suppressed by CIT + OTA. The combination of CIT + OTA also synergistically suppressed the expression of DNMT-3a and DNMT-3b. The combination of PAT + OTA reduced DNMT-3a expression, while PA + OTA reduced DNMT-3b expression. Lastly, MPA and PA slightly reduced HDAC-3 expression, while OTA in combination with CIT, PAT, MPA or PA synergistically suppressed HDAC-3 expression. The results of this study demonstrate that Penicillium mycotoxin exposure, specifically OTA and other mycotoxin combinations, can alter the expression of BoMac enzymes that are involved in epigenetic regulation. These findings suggest a potential novel regulatory mechanism by which mycotoxins can modulate macrophage function.

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Acknowledgements

Funding for this study was provided through the Ontario Ministry of Agriculture and Rural Affairs, Alltech Inc., and MITACs. Special thanks to Qiumei You for her technical support.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Animal and Poultry Science (APS), University of Guelph, 50 Stone Rd. East, Guelph, Ontario, N1G 2W1, Canada

    Se-Young Oh, Caroline G. Balch, Rachael L. Cliff, Bhawani S. Sharma, V. Margaret Quinton & Niel A. Karrow

  2. Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1, Canada

    Herman J. Boermans

  3. Alltech Inc. Canada, 20 Cutten Pl, Guelph, Ontario, N1G 4Z7, Canada

    H. V. L. N. Swamy

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  1. Se-Young Oh
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Oh, SY., Balch, C.G., Cliff, R.L. et al. Exposure to Penicillium mycotoxins alters gene expression of enzymes involved in the epigenetic regulation of bovine macrophages (BoMacs). Mycotoxin Res 29, 235–243 (2013). https://doi.org/10.1007/s12550-013-0174-y

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