Modulation of Mucin (MUC2, MUC5AC and MUC5B) mRNA Expression and Protein Production and Secretion in Caco-2/HT29-MTX Co-Cultures Following Exposure to Individual and Combined Aflatoxin M1 and Ochratoxin A

Toxins (Basel). 2019 Feb 23;11(2):132. doi: 10.3390/toxins11020132.

Abstract

Aflatoxin M1 (AFM1) and ochratoxin A (OTA), which widely coexist in milk, may pose a serious threat to human health. Mucin is a major component of the intestinal mucus layer, which plays an important role in maintaining intestinal mucosal homeostasis. However, the effect of mycotoxins AFM1 and OTA on intestinal mucin production is still not clear. This study aimed to investigate individual and interactive effects of mycotoxins AFM1 and OTA on the intestinal barrier and the mRNA expression of intestinal mucin (MUC2, MUC5AC and MUC5B) and on protein production in Caco-2/HT29-MTX cultures after 48 h of exposure. Our results show that individual mycotoxins and their mixtures significantly reduced intestinal cell viability and transepithelial electrical resistance (TEER) values, as well as significantly altered intestinal mucin mRNA expression and protein abundance. Moreover, OTA showed toxicity similar to AFM1 in cell viability and TEER value at the same concentration. When the two mycotoxins acted in combination, the synergistic effects observed in the assessment of cell viability and protein abundance in all mono- and co-cultures. In general, this study provides evidence that AFM1 and OTA can damage the intestine, and it contributes to optimized maximum permissible limits of mycotoxins in milk.

Keywords: Caco-2/HT29-MTX co-cultures; aflatoxin M1; interactive effects; mucin; ochratoxin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin M1 / toxicity*
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Coculture Techniques
  • HT29 Cells
  • Humans
  • Mucin 5AC / genetics*
  • Mucin 5AC / metabolism
  • Mucin-2 / genetics*
  • Mucin-2 / metabolism
  • Mucin-5B / genetics*
  • Mucin-5B / metabolism
  • Ochratoxins / toxicity*
  • RNA, Messenger / metabolism

Substances

  • MUC2 protein, human
  • MUC5AC protein, human
  • MUC5B protein, human
  • Mucin 5AC
  • Mucin-2
  • Mucin-5B
  • Ochratoxins
  • RNA, Messenger
  • ochratoxin A
  • Aflatoxin M1