Titanium dioxide nanoparticles induce emphysema-like lung injury in mice

Huei Wen Chen, Sheng Fang Su, Chiang Ting Chien, Wei Hsiang Lin, Sung Liang Yu, Cheng Chung Chou, Jeremy J.W. Chen, Pan Chyr Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

302 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)E1732-E1741
JournalFASEB Journal
Issue number13
Publication statusPublished - 2006 Nov
Externally publishedYes


  • Chemokines
  • Microarray
  • Nanotechnology
  • Placenta growth factor
  • Pulmonary emphysema

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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