Titanium Dioxide Particle Type and Concentration Influence the Inflammatory Response in Caco-2 Cells

Int J Mol Sci. 2016 Apr 16;17(4):576. doi: 10.3390/ijms17040576.


Titanium dioxide (TiO₂) nanoparticles are widely used in cosmetics, sunscreens, biomedicine, and food products. When used as a food additive, TiO₂ nanoparticles are used in significant amounts as white food-coloring agents. However, the effects of TiO₂ nanoparticles on the gastrointestinal tract remain unclear. The present study was designed to determine the effects of five TiO₂ particles of different crystal structures and sizes in human epithelial colorectal adenocarcinoma (Caco-2) cells and THP-1 monocyte-derived macrophages. Twenty-four-hour exposure to anatase (primary particle size: 50 and 100 nm) and rutile (50 nm) TiO₂ particles reduced cellular viability in a dose-dependent manner in THP-1 macrophages, but in not Caco-2 cells. However, 72-h exposure of Caco-2 cells to anatase (50 nm) TiO₂ particles reduced cellular viability in a dose-dependent manner. The highest dose (50 µg/mL) of anatase (100 nm), rutile (50 nm), and P25 TiO₂ particles also reduced cellular viability in Caco-2 cells. The production of reactive oxygen species tended to increase in both types of cells, irrespective of the type of TiO₂ particle. Exposure of THP-1 macrophages to 50 µg/mL of anatase (50 nm) TiO₂ particles increased interleukin (IL)-1β expression level, and exposure of Caco-2 cells to 50 µg/mL of anatase (50 nm) TiO₂ particles also increased IL-8 expression. The results indicated that anatase TiO₂ nanoparticles induced inflammatory responses compared with other TiO₂ particles. Further studies are required to determine the in vivo relevance of these findings to avoid the hazards of ingested particles.

Keywords: food additive; inflammation; intestinal epithelium; macrophage; nanoparticles; reactive oxygen species; titanium dioxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Line
  • Cell Survival / drug effects
  • Food Coloring Agents / adverse effects*
  • Humans
  • Inflammation / etiology*
  • Inflammation / immunology
  • Interleukin-1beta / immunology
  • Interleukin-8 / immunology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology*
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Nanoparticles / adverse effects*
  • Particle Size
  • Reactive Oxygen Species / immunology
  • Titanium / adverse effects*
  • Titanium / immunology


  • Food Coloring Agents
  • Interleukin-1beta
  • Interleukin-8
  • Reactive Oxygen Species
  • titanium dioxide
  • Titanium