Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles

J Biomed Mater Res A. 2011 Jan;96(1):221-9. doi: 10.1002/jbm.a.32976. Epub 2010 Nov 9.


In an effort to examine signaling pathway of inflammation of the mouse liver caused by intragastric administration of titanium dioxide nanoparticles (NPs), we assessed Toll-like receptor-2 (TLR2), TLR-4, IκB kinase (IKK-α, IKK-β), IκB nucleic factor-κB (NF-κB), NF-κBP52, NF-κBP65, tumor necrosis factor-α (TNF-α), NF-κB-inducible kinase (NIK), interleukin-2 (IL-2), biochemical parameters of liver functions, and histopathological changes and liver ultrastructure in the TiO(2) NPs-treated mice. The results showed the titanium accumulation in liver, histopathological changes and hepatocytes apoptosis of mice liver, and the liver function damaged by TiO(2) NPs. The real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay analyses showed that TiO(2) NPs can significantly increase the mRNA and protein expression of TLR2 and TLR4 and several inflammatory cytokines, including IKK1, IKK2, NF-κB, NF-κBP52, NF-κBP65, TNF-α, and NIK, and TiO(2) NPs can significantly decrease the mRNA and protein expression of IκB and IL-2. The results of this study added to our understanding of TiO(2) NPs-induced liver toxicity. It implied that the signaling pathway of liver injury in the TiO(2) NPs-stimulated mouse liver sequentially might occur via activation of TLRs→NIK→IκB kinase→NF-κB→TNF-α→inflammation→apoptosis→liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cytokines / immunology
  • Female
  • Inflammation / metabolism*
  • Liver / cytology
  • Liver / drug effects*
  • Liver / immunology*
  • Metal Nanoparticles / chemistry*
  • Mice
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • Titanium / chemistry*
  • Titanium / pharmacology*
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 4 / immunology


  • Biocompatible Materials
  • Cytokines
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • titanium dioxide
  • Titanium