Titanium Dioxide Particle Type and Concentration Influence the Inflammatory Response in Caco-2 Cells.
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.
Department of Human Nutrition, School of Life Studies, Sugiyama Jogakuen University, Nagoya 464-8662, Japan. t-saeko@sugiyama-u.ac.jp.|Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. t-saeko@sugiyama-u.ac.jp.
Saeko
S
Tada-Oikawa
Department of Occupational and Environmental Health, Tokyo Univeristy of Science, Noda 278-8510, Japan. gak@rs.tus.ac.jp.
Gaku
G
Ichihara
Department of Human Nutrition, School of Life Studies, Sugiyama Jogakuen University, Nagoya 464-8662, Japan. fha12aa100@st.sugiyama-u.ac.jp.
Hitomi
H
Fukatsu
Department of Human Nutrition, School of Life Studies, Sugiyama Jogakuen University, Nagoya 464-8662, Japan. sya12aa057@st.sugiyama-u.ac.jp.
Yuka
Y
Shimanuki
Department of Human Nutrition, School of Life Studies, Sugiyama Jogakuen University, Nagoya 464-8662, Japan. tna12aa069@st.sugiyama-u.ac.jp.
Natsuki
N
Tanaka
Department of Occupational and Environmental Health, Tokyo Univeristy of Science, Noda 278-8510, Japan. eri.watanabe.0503@gmail.com.
Eri
E
Watanabe
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. suzujohn@yahoo.co.jp.
Yuka
Y
Suzuki
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. 309111@m.mie-u.ac.jp.
Masahiko
M
Murakami
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. izuoka@innov.mie-u.ac.jp.
Kiyora
K
Izuoka
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. jchang@suda.edu.cn.
Jie
J
Chang
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. wendywu1206@163.com.
Wenting
W
Wu
Department of Human Genomics, Life Scinece Research Center, Mie University, Tsu 514-8507, Japan. yamada@gene.mie-u.ac.jp.
Yoshiji
Y
Yamada
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. saho@gene.mie-u.ac.jp.|Department of Human Genomics, Life Scinece Research Center, Mie University, Tsu 514-8507, Japan. saho@gene.mie-u.ac.jp.
Sahoko
S
Ichihara
D018938:Caco-2 Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005505:Food Coloring Agents / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D053758:Nanoparticles / Q000009:adverse effects*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000276:immunology; D014025:Titanium / Q000009:adverse effects* / Q000276:immunology
D005505:Food Coloring Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium
food additive; inflammation; intestinal epithelium; macrophage; nanoparticles; reactive oxygen species; titanium dioxide