TY - JOUR
T1 - Titanium dioxide nanoparticles induce emphysema-like lung injury in mice
AU - Chen, Huei Wen
AU - Su, Sheng Fang
AU - Chien, Chiang Ting
AU - Lin, Wei Hsiang
AU - Yu, Sung Liang
AU - Chou, Cheng Chung
AU - Chen, Jeremy J.W.
AU - Yang, Pan Chyr
PY - 2006/11
Y1 - 2006/11
N2 - Titanium dioxide nanoparticles (nano-TiO2) have been widely used as a photocatalyst in air and water cleaning. However, these nanoparticles inhalation can induce pulmonary toxicity and its mechanism is not fully understood. In this study we investigated the pulmonary toxicity of nanoTiO 2 and its molecular pathogenesis. The adult male ICR mice were exposed to intratracheal single dose of 0.1 or 0.5 mg nanoTiO2 (19-21 nm) and lung tissues were collected at 3rd day, 1st wk, and 2nd wk for morphometric, microarray gene expression, and pathway analyses. NanoTiO 2 can induce pulmonary emphysema, macrophages accumulation, extensive disruption of alveolar septa, type II pneumocyte hyperplasia, and epithelial cell apoptosis. NanoTiO2 induced differential expression of hundreds of genes include activation of pathways involved in cell cycle, apoptosis, chemokines, and complement cascades. In particular, nanoTiO2 up-regulates placenta growth factor (PlGF) and other chemokines (CXCL1, CXCL5, and CCL3) expressions that may cause pulmonary emphysema and alveolar epithelial cell apoptosis. Cultured human THP-1 cell-derived macrophages treated with nanoTiO2 in vitro also resulted in upregulations of PlGF, CXCL1, CXCL5, and CCL3. These results indicated that nanoTiO2 can induce severe pulmonary emphysema, which may be caused by activation of PlGF and related inflammatory pathways.
AB - Titanium dioxide nanoparticles (nano-TiO2) have been widely used as a photocatalyst in air and water cleaning. However, these nanoparticles inhalation can induce pulmonary toxicity and its mechanism is not fully understood. In this study we investigated the pulmonary toxicity of nanoTiO 2 and its molecular pathogenesis. The adult male ICR mice were exposed to intratracheal single dose of 0.1 or 0.5 mg nanoTiO2 (19-21 nm) and lung tissues were collected at 3rd day, 1st wk, and 2nd wk for morphometric, microarray gene expression, and pathway analyses. NanoTiO 2 can induce pulmonary emphysema, macrophages accumulation, extensive disruption of alveolar septa, type II pneumocyte hyperplasia, and epithelial cell apoptosis. NanoTiO2 induced differential expression of hundreds of genes include activation of pathways involved in cell cycle, apoptosis, chemokines, and complement cascades. In particular, nanoTiO2 up-regulates placenta growth factor (PlGF) and other chemokines (CXCL1, CXCL5, and CCL3) expressions that may cause pulmonary emphysema and alveolar epithelial cell apoptosis. Cultured human THP-1 cell-derived macrophages treated with nanoTiO2 in vitro also resulted in upregulations of PlGF, CXCL1, CXCL5, and CCL3. These results indicated that nanoTiO2 can induce severe pulmonary emphysema, which may be caused by activation of PlGF and related inflammatory pathways.
KW - Chemokines
KW - Microarray
KW - Nanotechnology
KW - Placenta growth factor
KW - Pulmonary emphysema
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U2 - 10.1096/fj.06-6485fje
DO - 10.1096/fj.06-6485fje
M3 - Article
C2 - 17023518
AN - SCOPUS:33845642987
SN - 0892-6638
VL - 20
SP - E1732-E1741
JO - FASEB Journal
JF - FASEB Journal
IS - 13
ER -