Resolvin D1 and E1 alleviate the progress of hepatitis toward liver cancer in long-term concanavalin A-induced mice through inhibition of NF-κB activity
Autor: | Jianhui Zhou, Xiaoli Hua, Rui Yang, Haoyu Kuang |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Cancer Research Docosahexaenoic Acids Pharmacology CD8-Positive T-Lymphocytes Proinflammatory cytokine Hepatitis 03 medical and health sciences Mice Liver Neoplasms Experimental medicine Concanavalin A Animals Liver X receptor Liver injury biology General Medicine medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Eicosapentaenoic Acid Immunology biology.protein Cytokines Cytokine secretion Tumor necrosis factor alpha Liver cancer |
Zdroj: | Oncology reports. 35(1) |
ISSN: | 1791-2431 |
Popis: | Resolvins, an endogenous lipid mediator derived from eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) of fish oil, has been reported to have anti-inflammatory and antitumor effect in various pathogenic processes. However, there are no studies about the effects of resolvin D1 and E1 on concanavalin A-induced hepatitis. Hence, the present study is to illustrate whether resolvin D1 and E1 inhibit concanavalin A-induced liver injury, liver cancer and underlying mechanisms by which they may recover. C57BL/6 mice were pretreated with resolvin D1 and E1 for 4 h, and then injected with concanavalin A for 12 h. Subsequently, blood and liver tissue were collected at 0, 2, 4, 8 and 12 h for different analysis. Analysis of inflammatory cytokines indicated that the inhibition of necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-1β and IL-6 could be performed by resolvin D1 and E1. Moreover, Toll-like receptor (TLR) 4 expression, NF-κB and AP-1 activity also have been confirmed to have key roles in the development of liver injury. They were significantly suppressed in the treatment group, compared to model. In addition, resolvin D1 and E1 markedly downregulated CD4+ and CD8+ cell infiltration in the liver. A long-term concanavalin A treatment for 32 weeks was performed to analyze the changes of hepatitis to liver cancer and the antitumor effect of resolving D1 and E1. These results indicated that resolvin D1 and E1 prevent concanavalin A-induced liver injury and the changes of hepatitis to liver cancer in mice through inhibition of inflammatory cytokine secretion and NF-κB/AP-1 activity. Thus, they could be novel target to be considered in the process of finding sufficient drug to protect against various forms of hepatitis and liver cancer. |
Databáze: | OpenAIRE |
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