RESUMO
In recent years, the popularity of dietary nanoparticles (NPs) in the food industry as additives has raised concerns because of the lack of knowledge about potential adverse health outcomes ensuing from the interactions of NPs with components of the food matrix and gastrointestinal system. In this study, we used a transwell culture system that consisted of human colorectal adenocarcinoma (Caco-2) cells in the apical insert and Laboratory of Allergic Diseases 2 mast cells in the basal compartment to study the effect of NPs on milk allergen delivery across the epithelial layer, mast cell responses and signaling between epithelial and mast cells in allergenic inflammation. A library of dietary particles (silicon dioxide NPs, titanium dioxide NPs and silver NPs) that varied in particle size, surface chemistry and crystal structures with or without pre-exposure to milk was used in this investigation. Milk-interacted particles were found to acquire surface corona and increased the bioavailability of milk allergens (casein and ß-lactoglobulin) across the intestinal epithelial layer. The signaling between epithelial cells and mast cells resulted in significant changes in the early phase and late-phase activation of the mast cells. This study suggested that antigen challenge in mast cells with the presence of dietary NPs may cause the transition of allergic responses from an immunoglobulin E (IgE)-dependent mechanism to a mixed mechanism (both IgE-dependent and IgE-independent mechanisms).
Assuntos
Proteínas do Leite , Nanopartículas , Humanos , Células CACO-2 , Alérgenos , Nanopartículas/química , Imunoglobulina ERESUMO
Nanoparticles (NPs) are increasingly being used in the food sector, yet little is known about the potential health risks associated with oral exposure to dietary NPs. In this study, the most widely used NPs in food industry including food grade silicon dioxide (SiO2), titanium dioxide (TiO2) and silver (Ag), along with their non-food grade and bulk counterparts, are characterized for physicochemical properties and molecular, cellular, and intracellular effects on human intestinal epithelial cells (Caco-2 and HIEC-6). Silver NPs are the most cytotoxic and induce significant cellular changes in oxidative stress, Ca2+ flux and mitochondria function, leading to cellular junction disruption at the lowest exposure concentration. At higher testing concentrations, NPs but not microparticles of SiO2 and TiO2 cause sublethal cellular responses and remodel tight junctions without impairing epithelial integrity. To relate the cellular results to key events in GI disorder progression, NPs are exposed to an in vitro co-culture model for cow's milk allergy comprised of Caco-2 and allergy sera-primed mast cells (LUVA). All particle treatments increase the allergen delivery across intestinal epithelium and subsequent allergy responses. Overall, the study has identified a particle-dependent alteration in intestinal epithelium and highlighted potential safety concerns of dietary NPs.