Abstract | OBJECTIVE: METHODS: C57BL/6 mice were exposed to ConA via tail vein injection and injected intraperitoneally with Nec-1 or vehicle. Levels of serum liver enzymes and histopathology were determined. Levels of inflammatory cytokines with ConA-induced hepatitis were determined with real-time polymerase chain reaction (real-time PCR). The expression of TNF- α , RIP1, and LC3 was detected with immunohistochemical staining. The expression of TNF- α , IFN- γ , IL2, IL6, caspase 3, RIP1, beclin-1, and LC3 protein was assessed by immunofluorescence and western blotting. Autophagosomes were observed with transmission electron microscopy (TEM). RESULTS: Amelioration in liver functions and histopathological changes and the suppression of inflammatory cytokine production were observed in Nec-1-injected mice. Western blotting analysis showed that the expression of TNF- α , IFN- γ , IL2, IL6, and RIP1 was significantly reduced in the Nec-1-injected mice, which was confirmed by immunofluorescence and immunohistochemistry. Autophagosome formation was significantly reduced by Nec-1 treatment, as the expression of beclin-1 and LC3, determined with immunofluorescence and western blotting. CONCLUSION: These results demonstrate that Nec-1 prevents ConA-induced liver injury via RIP1-related and autophagy-related pathways.
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Authors | Yingqun Zhou, Weiqi Dai, Chunlei Lin, Fan Wang, Lei He, Miao Shen, Ping Chen, Chenfen Wang, Jie Lu, Ling Xu, Xuanfu Xu, Chuanyong Guo |
Journal | Mediators of inflammation
(Mediators Inflamm)
Vol. 2013
Pg. 706156
( 2013)
ISSN: 1466-1861 [Electronic] United States |
PMID | 24198446
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- GTPase-Activating Proteins
- Imidazoles
- Indoles
- Map1lc3b protein, mouse
- Microtubule-Associated Proteins
- Ralbp1 protein, mouse
- Tumor Necrosis Factor-alpha
- necrostatin-1
- Concanavalin A
- Transaminases
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Topics |
- Animals
- Autophagy
- Chemical and Drug Induced Liver Injury
(drug therapy)
- Concanavalin A
(toxicity)
- Cytokines
(metabolism)
- Disease Models, Animal
- GTPase-Activating Proteins
(metabolism)
- Gene Expression Profiling
- Gene Expression Regulation
- Imidazoles
(therapeutic use)
- Indoles
(therapeutic use)
- Liver
(pathology)
- Liver Failure, Acute
(drug therapy, prevention & control)
- Male
- Mice
- Mice, Inbred C57BL
- Microscopy, Electron, Transmission
- Microtubule-Associated Proteins
(metabolism)
- Necrosis
(pathology)
- Phagosomes
(metabolism)
- Real-Time Polymerase Chain Reaction
- Transaminases
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
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