title: Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles.
abstract: 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.
authors.affiliation: Medical College, Soochow University, Suzhou, People's Republic of China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Cui
authors.forename: Huiting
authors.initials: H
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Duan
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Gong
authors.forename: Renping
authors.initials: R
authors.lastname: Hu
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Hong
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D014025:Titanium / Q000737:chemistry* / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C009495:titanium dioxide; D014025:Titanium