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Cellular Response to Titanium Dioxide Nanoparticles in Intestinal Epithelial Caco-2 Cells is Dependent on Endocytosis-Associated Structures and Mediated by EGFR
- Source :
- Nanomaterials; Volume 7; Issue 4; Pages: 79, Nanomaterials
- Publication Year :
- 2017
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2017.
-
Abstract
- Titanium dioxide (TiO2) is one of the most applied nanomaterials and widely used in food and non-food industries as an additive or coating material (E171). It has been shown that E171 contains up to 37% particles which are smaller than 100 nm and that TiO2 nanoparticles (NPs) induce cytotoxicity and inflammation. Using a nuclear factor Kappa-light-chain enhancer of activated B cells (NF-κB) reporter cell line (Caco-2nfkb-RE), Real time polymerase chain reaction (PCR), and inhibition of dynamin and clathrin, it was shown that cellular responses induced by 5 nm and 10 nm TiO2 NPs (nominal size) depends on endocytic processes. As endocytosis is often dependent on the epithelial growth factor receptor (EGFR), further investigations focused on the involvement of EGFR in the uptake of TiO2 NPs: (1) inhibition of EGFR reduced inflammatory markers of the cell (i.e., nuclear factor (NF)-κB activity, mRNA of IL8, CCL20, and CXCL10); and (2) exposure of Caco-2 cells to TiO2 NPs activated the intracellular EGFR cascade beginning with EGFR-mediated extracellular signal-regulated kinases (ERK)1/2, and including transcription factor ELK1. This was followed by the expression of ERK1/2 target genes CCL2 and CXCL3. We concluded that TiO2 NPs enter the cell via EGFR-associated endocytosis, followed by activation of the EGFR/ERK/ELK signaling pathway, which finally induces NF-κB. No changes in inflammatory response are observed in Caco-2 cells exposed to 32 nm and 490 nm TiO2 particles.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Materials science
General Chemical Engineering
EGFR
Endocytic cycle
Endocytosis
Clathrin
Article
03 medical and health sciences
0302 clinical medicine
Growth factor receptor
endocytosis
General Materials Science
Dynamin
biology
ERK1/2
Cell biology
030104 developmental biology
inflammation
030220 oncology & carcinogenesis
biology.protein
intestinal epithelial cells
Signal transduction
titanium dioxide nanoparticles
Intracellular
Subjects
Details
- Language :
- English
- ISSN :
- 20794991
- Database :
- OpenAIRE
- Journal :
- Nanomaterials; Volume 7; Issue 4; Pages: 79
- Accession number :
- edsair.doi.dedup.....63616ef339c5a54fa4d54decf4ab2d32
- Full Text :
- https://doi.org/10.3390/nano7040079