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Single versus repeated exposure to human polarized intestinal epithelial monolayers for in vitro protein hazard

B B Lanter1, A D Eaton1, J M Roper2

  • 1Department of Pediatrics, Mucosal Immunology & Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|July 10, 2019
PubMed

Insights

Repeated protein exposures to human intestinal cells (IECs) more significantly impact barrier integrity and cell viability than single exposures. This highlights the importance of considering exposure frequency in toxicity assessments.

Area of Science:

  • Toxicology
  • Cell Biology
  • Gastroenterology

Background:

  • Human intestinal epithelial cell (IEC) lines cultured on Transwell® filters model the gut barrier.
  • Previous studies show single protein exposures can differentiate hazardous from non-hazardous substances.

Purpose of the Study:

  • To evaluate if repeated protein exposures alter intestinal barrier integrity or cell viability compared to single exposures.
  • To assess the dose-response relationship of protein toxicity in a human IEC model.

Main Methods:

  • Cultured human IEC polarized monolayers on Transwell® filters were exposed to hazardous or non-hazardous proteins.
  • Proteins included Clostridium difficile toxin A, Streptolysin O, and others.
  • Monolayers underwent nine exposures over 30 days, compared to single exposures.

Main Results:

  • Repeated exposures to hazardous proteins caused more pronounced reductions in barrier integrity and cell viability than single exposures.
  • Some hazardous proteins only affected IEC monolayers after repeated exposures.
  • Non-hazardous proteins elicited minimal responses, regardless of exposure frequency.

Conclusions:

  • Cultured human IEC monolayers effectively differentiate hazardous from non-hazardous proteins.
  • Repeated exposures reveal a greater magnitude of toxicological response than single exposures in this model.

Keywords:
CytotoxicityIntestinal epithelial cellsRepeated dose

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