The murine enterocyte cell line Mode-K is a novel and reliable in vitro model for studies on gluten toxicity

Food Chem Toxicol. 2020 Jun:140:111331. doi: 10.1016/j.fct.2020.111331. Epub 2020 Apr 15.

Abstract

The resemblance of physiological traits of cell lines with their target/original tissue is an important prerequisite for the choice of the in vitro model. Although cytoprotective defenses, activated by the nuclear factor erythroid 2-related factor2 (Nrf2), have a preeminent importance in intestinal protection, nevertheless their levels inin vitro models have been never compared with those of their original tissue. Basal level of Nrf2-mediated defenses in murine enterocyte cells (Mode-K) and in human colon adenocarcinoma cells -at differentiated (DCaco2) or confluent stage (CCaco2)- were compared with those found in mouse or human duodenum. The pro-oxidant and cytotoxic effects of peptic-tryptic digest of gluten prepared from wheat bread (PT-b), einkorn (PT-e) or durum wheat (PT-d) were evaluated in Mode-k and DCaco2 by combining enzymatic, immune-enzymatic and real-time PCR assay. The results presented reveal that Mode-k cells resemble cytoprotective defenses of human/murine duodenum and are more susceptible to pro-oxidant, cytotoxic and pro-inflammatory effect of gliadin digest (in comparison with Caco2). Prolamins digests from the considered wheat exhibit different inhibitory effect on Nrf2-mediated defenses (PT-b > PT-e > PT-d). These data indicate, for the first time, that Mode-k are a reliable model for investigating wheat prolamins toxicity and for evaluating the signaling pathway of gluten-associated disease.

Keywords: Celiac disease; Cyto-protections; Gluten toxicity; In vitro models; Mode-K cells; Nuclear erythroid related factor 2.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Differentiation
  • Cell Line
  • Duodenum / drug effects
  • Enterocytes / cytology
  • Enterocytes / drug effects*
  • Gliadin / toxicity
  • Glutens / toxicity*
  • Humans
  • In Vitro Techniques
  • Mice
  • Models, Biological
  • Triticum / chemistry

Substances

  • Glutens
  • Gliadin