Pyroptosis-Mediated Damage Mechanism by Deoxynivalenol in Porcine Small Intestinal Epithelial Cells

Toxins (Basel). 2023 Apr 19;15(4):300. doi: 10.3390/toxins15040300.

Abstract

Deoxynivalenol (DON) is known as a vomitoxin, which frequently contaminates feedstuffs, such as corn, wheat, and barley. Intake of DON-contaminated feed has been known to cause undesirable effects, including diarrhea, emesis, reduced feed intake, nutrient malabsorption, weight loss, and delay in growth, in livestock. However, the molecular mechanism of DON-induced damage of the intestinal epithelium requires further investigation. Treatment with DON triggered ROS in IPEC-J2 cells and increased the mRNA and protein expression levels of thioredoxin interacting protein (TXNIP). To investigate the activation of the inflammasome, we confirmed the mRNA and protein expression levels of the NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 (CASP-1). Moreover, we confirmed that caspase mediates the mature form of interleukin-18, and the cleaved form of Gasdermin D (GSDMD) was increased. Based on these results, our study suggests that DON can induce damage through oxidative stress and pyroptosis in the epithelial cells of the porcine small intestine via NLRP3 inflammasome.

Keywords: deoxynivalenol; intestinal epithelial cell; porcine; pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Caspases / metabolism
  • Epithelial Cells
  • Inflammasomes* / metabolism
  • Intestine, Small / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pyroptosis*
  • RNA, Messenger
  • Swine

Substances

  • deoxynivalenol
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Caspase 1
  • Caspases
  • RNA, Messenger

Grants and funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1I1A3070740).