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Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
Published on: March 10, 2017
Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles
Yaling Cui1, Huiting Liu, Min Zhou
1Medical College, Soochow University, Suzhou, People's Republic of China.
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.
Insights
Titanium dioxide nanoparticles (TiO(2) NPs) cause liver inflammation and damage in mice by activating specific signaling pathways. This study elucidates the inflammatory cascade initiated by TiO(2) NPs in the liver.
Area of Science:
- Toxicology
- Nanomedicine
- Immunology
Background:
- Titanium dioxide nanoparticles (TiO(2) NPs) are widely used, raising concerns about their potential toxicity.
- Understanding the molecular mechanisms of TiO(2) NP-induced liver injury is crucial for risk assessment.
Purpose of the Study:
- To investigate the signaling pathway of inflammation in mouse liver following intragastric administration of TiO(2) NPs.
- To assess the impact of TiO(2) NPs on liver function, histopathology, and cellular ultrastructure.
Main Methods:
- Mice were administered TiO(2) NPs intragastrically.
- Analysis included Toll-like receptor (TLR) expression, inflammatory cytokine levels (mRNA and protein), liver function tests, and histopathological examination.
- Real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were employed.
Main Results:
- TiO(2) NPs accumulated in the liver, leading to histopathological changes, hepatocyte apoptosis, and impaired liver function.
- Increased mRNA and protein expression of TLR2, TLR4, IκB kinase (IKKα, IKKβ), nuclear factor-κB (NF-κB) components (NF-κBP52, NF-κBP65), NF-κB-inducible kinase (NIK), and tumor necrosis factor-α (TNF-α) were observed.
- Decreased mRNA and protein expression of IκB and interleukin-2 (IL-2) were noted.
Conclusions:
- TiO(2) NPs induce liver toxicity through a sequential signaling pathway involving TLRs, NIK, IκB kinase, NF-κB, and TNF-α, culminating in inflammation, apoptosis, and liver injury.
- This study enhances understanding of the molecular mechanisms underlying TiO(2) NP-induced hepatotoxicity.
