Effects of ultrafine TiO2 particles on gene expression profile in human keratinocytes without illumination: involvement of extracellular matrix and cell adhesion.
Assessing in vitro cellular responses to molecular events is an effective mean to elucidate the toxicological behavior of the ultrafine nanoparticles. In this study, we utilized the DNA microarray analysis technique to determine the gene expression profiles of the human keratinocyte HaCaT cells exposed to anatase titanium dioxide (TiO(2)) particles of different (7 nm, 20 nm and 200 nm) average diameters without illumination. Cells were incubated for 24 h with TiO(2) particles, which were dispersed in the culture medium and size-fractionated such that the concentration of titanium in all the fractionated samples was nearly equivalent. According to the cluster analysis, only genes involved in the 'inflammatory response' and 'cell adhesion', but not the genes involved in 'oxidative stress' and 'apoptosis', were over-represented among the genes that were up-regulated in HaCaT cells. After 24 h exposure to ultrafine 7 nm TiO(2) particles, we observed altered expression levels of genes involved in matrix metalloproteinase activity (MMP-9 and MMP-10) and cell adhesion (fibronectin FN-1, integrin ITGB-6, and mucin MUC-4). These results suggest that the ultrafine TiO(2) particles without illumination have no significant impact on ROS-associated oxidative damage, but affect the cell-matrix adhesion in keratinocytes for extracellular matrix remodeling.
Fujita
Katsuhide
K
Health Technology Research Center, National Institute of Advanced Industrial Science and Technology, Onogawa 16-1, Tsukuba, Ibaraki 305-8569, Japan. ka-fujita@aist.go.jp
Horie
Masanori
M
Kato
Haruhisa
H
Endoh
Shigehisa
S
Suzuki
Mie
M
Nakamura
Ayako
A
Miyauchi
Arisa
A
Yamamoto
Kazuhiro
K
Kinugasa
Shinichi
S
Nishio
Keiko
K
Yoshida
Yasukazu
Y
Iwahashi
Hitoshi
H
Nakanishi
Junko
J
D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D004396:Coloring Agents; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D013778:Tetrazolium Salts; D013844:Thiazoles; D014025:Titanium / Q000633:toxicity*
D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C009495:titanium dioxide; D004247:DNA; D014025:Titanium; D020782:Matrix Metalloproteinases; C022616:thiazolyl blue