title: Molecular mechanism of silver nanoparticles in human intestinal cells.
abstract: Silver nanoparticles are used in consumer products like food contact materials, drinking water technologies and supplements, due to their antimicrobial properties. This leads to an oral uptake and exposure of intestinal cells. In contrast to other studies we found no apoptosis induction by surfactant-coated silver nanoparticles in the intestinal cell model Caco-2 in a previous study, although the particles induced oxidative stress, morphological changes and cell death. Therefore, this study aimed to analyze the molecular mechanism of silver nanoparticles in Caco-2 cells. We used global gene expression profiling in differentiated Caco-2 cells, supported by verification of the microarray data by quantitative real-time RT-PCR and microscopic analysis, impedance measurements and assays for apoptosis and oxidative stress. Our results revealed that surfactant-coated silver nanoparticles probably affect the cells by outside-in signaling. They induce oxidative stress and have an influence on canonical pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight junctions, thereby inducing transcription factors like AP1, NFkB and NRF2, which mediate cellular reactions in response to oxidative stress and metal ions and induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic cell death, especially in the intestine, can cause inflammation and influence the mucosal immune response.
authors.affiliation: a Department Food Safety , Federal Institute for Risk Assessment , Berlin , Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Böhmert
authors.affiliation: a Department Food Safety , Federal Institute for Risk Assessment , Berlin , Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Niemann
authors.affiliation: a Department Food Safety , Federal Institute for Risk Assessment , Berlin , Germany.
authors.forename: Dajana
authors.initials: D
authors.lastname: Lichtenstein
authors.affiliation: a Department Food Safety , Federal Institute for Risk Assessment , Berlin , Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Juling
authors.affiliation: a Department Food Safety , Federal Institute for Risk Assessment , Berlin , Germany.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lampen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000187:drug effects* / Q000648:ultrastructure; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012834:Silver / Q000737:chemistry / Q000633:toxicity*
chemical_list: D012834:Silver
keywords: Caco-2 cells; in vitro; microarray; oral; silver nanoparticles