Cellular Response to Titanium Dioxide Nanoparticles in Intestinal Epithelial Caco-2 Cells is Dependent on Endocytosis-Associated Structures and Mediated by EGFR

Krüger, Kristin; Schrader, Katrin; Klempt, Martin

doi:10.3390/nano7040079

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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

Kristin Krüger

Katrin Schrader

and

Martin Klempt

Max Rubner-Institut (MRI), Federal Research Institute for Nutrition and Food, Department of Safety and Quality of Milk and Fish Products, Hermann-Weigmann-Straße 1, 24103 Kiel, Germany

Author to whom correspondence should be addressed.

Academic Editors: Dong-Wook Han and Wojciech Chrzanowski

Nanomaterials 2017, 7(4), 79; https://doi.org/10.3390/nano7040079

Received: 3 March 2017 / Revised: 5 April 2017 / Accepted: 5 April 2017 / Published: 7 April 2017

(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)

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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-2^nfkb-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. View Full-Text

Keywords: titanium dioxide nanoparticles; intestinal epithelial cells; inflammation; endocytosis; EGFR; ERK1/2

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Krüger, K.; Schrader, K.; Klempt, M. Cellular Response to Titanium Dioxide Nanoparticles in Intestinal Epithelial Caco-2 Cells is Dependent on Endocytosis-Associated Structures and Mediated by EGFR. Nanomaterials 2017, 7, 79. https://doi.org/10.3390/nano7040079

AMA Style

Krüger K, Schrader K, Klempt M. Cellular Response to Titanium Dioxide Nanoparticles in Intestinal Epithelial Caco-2 Cells is Dependent on Endocytosis-Associated Structures and Mediated by EGFR. Nanomaterials. 2017; 7(4):79. https://doi.org/10.3390/nano7040079

Chicago/Turabian Style

Krüger, Kristin, Katrin Schrader, and Martin Klempt. 2017. "Cellular Response to Titanium Dioxide Nanoparticles in Intestinal Epithelial Caco-2 Cells is Dependent on Endocytosis-Associated Structures and Mediated by EGFR" Nanomaterials 7, no. 4: 79. https://doi.org/10.3390/nano7040079

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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

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