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

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, I kappa B kinase (IKK-alpha, IKK-beta), I kappa B nucleic factor-kappa B (NF-kappa B), NF-kappa BP52, NF-kappa BP65, tumor necrosis factor-alpha (TNF-alpha), NF-kappa B-inducible kinase (NIK), interleukin-2 (IL-2), biochemical parameters of liver functions, and histopathological changes and liver ultrastructure in the TiO2 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 TiO2 NPs. The real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay analyses showed that TiO2 NPs can significantly increase the mRNA and protein expression of TLR2 and TLR4 and several inflammatory cytokines, including IKK1, IKK2, NF-kappa B, NF-kappa BP52, NF-kappa BP65, TNF-alpha, and NIK, and TiO2 NPs can significantly decrease the mRNA and protein expression of I kappa B and IL-2. The results of this study added to our understanding of TiO2 NPs-induced liver toxicity. It implied that the signaling pathway of liver injury in the TiO2 NPs-stimulated mouse liver sequentially might occur via activation of TLRs -> NIK -> I kappa B kinase -> NF-kappa B -> TNF-alpha -> inflammation -> apoptosis -> liver injury. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 96A: 221-229, 2011.