Investigations on the toxic and proinflammatory effects of food-relevant nanoparticles using a novel in vitro model of the healthy and inflamed intestine

• Applicant: Dr. Kirsten Britta Gerloff
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 198173593

The use of engineered nanoparticles (NP) for food and food-related products is increasing rapidly. However, their potential hazards in both the healthy and the inflamed intestine upon ingestion are poorly investigated, and appropriate in vitro systems to study such effects are rare. Furthermore, the few studies that currently address this issue neglected the importance of the mucus layer herein, which is the first physical and immunological barrier of the intestinal epithelium. Consequently, mucins might impede ingested NP from entering the epithelium, preventing their potentially adverse effects. Alternatively, NP might influence the structure or function of mucins. Therefore, the proposed project extension will be used to optimise and utilise a recently developed ex vivo model consisting of human colonic tissue explants. These samples can be applied to study translocation of NP through the mucus layer, their cellular uptake as well possible proinflammatory and cytotoxic effects. To mimic intestinal inflammation, activated human neutrophils or a combination of relevant proinflammatory cytokines will be applied to the explants. The influence of such acute inflammation on the amplification of NP induced responses will be determined. Moreover, two current projects will be finalised. A co-culture model for the inflamed epithelium using differentiated epithelial cells and primary human neutrophils could be optimised. This model can now be applied to further assess the toxicity of NP to cells experiencing inflammatory stress. Also, the influence of cell surface mucins on NP induced adverse effects is currently investigated and requires only finalising experiments.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Host: Professor Michael McGuckin, Ph.D.