Ongoing inflammation enhances the toxicity of engineered nanomaterials: Application of an in vitro co-culture model of the healthy and inflamed intestine

Angela A. M. Kämpfer, Patricia Urbán, Rita La Spina, Isaac Ojea Jiménez, Nilesh Kanase, Vicki Stone, Agnieszka Kinsner-Ovaskainen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chronic inflammatory conditions can negatively impact intestinal barrier function and affect the epithelium's interaction with nano-sized materials. We demonstrate the application of a Caco-2/THP-1 co-culture mimicking the intestine in healthy (i.e. stable) or inflamed state in nanotoxicological research. The co-cultures were exposed to non-toxic concentrations of silver nanoparticles (AgNPs) or silver nitrate (AgNO 3) for 24 h. The barrier integrity and cytokine release as well as necrotic and apoptotic cell death were investigated. AgNPs and AgNO 3 most strongly affected the inflamed co-culture. Higher concentrations of AgNPs induced a significant increase in barrier integrity in the inflamed but not the stable co-culture. Necrotic and apoptotic cell death was detected in both conditions but were significantly more pronounced in the inflamed condition. The exposure to AgNO 3 affected barrier integrity in all experimental set-ups, but caused nuclear condensation only in the Caco-2 monoculture and the inflamed co-culture. AgNPs reduced the release of monocyte chemoattractant protein-1 in the stable model. Clear differences were observed in the effects of AgNPs and AgNO 3 in relation to the model's health status. The results suggest an increased vulnerability of the inflamed epithelial barrier towards AgNPs underlining the importance to consider the intestinal health status in the safety assessment of nanomaterials.

Original languageEnglish
Article number104738
JournalToxicology in Vitro
Volume63
Early online date21 Nov 2019
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Caco-2
  • Inflammatory bowel disease
  • Intestinal in vitro co-culture
  • Silver nanoparticles
  • THP-1

ASJC Scopus subject areas

  • Toxicology

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