Treatment of experimental non-alcoholic steatohepatitis by targeting α7 nicotinic acetylcholine receptor-mediated inflammatory responses in mice
| Autor: | Xiao‑Juan Tong, Yue‑Ping Ding, Ying‑Chao Liu, Zhou Zhou, Xiao‑Mei Chen, Cui‑Lan Tang, Fu‑Qiang Li |
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| Rok vydání: | 2015 |
| Předmět: |
Male
MAPK/ERK pathway Nicotine Cancer Research medicine.medical_specialty alpha7 Nicotinic Acetylcholine Receptor Population Anti-Inflammatory Agents Pharmacology Diet High-Fat Biochemistry Cell Line Mice Non-alcoholic Fatty Liver Disease Internal medicine Genetics medicine Animals Nicotinic Agonists education Interleukin 6 Molecular Biology Acetylcholine receptor Inflammation education.field_of_study biology Interleukin-6 Tumor Necrosis Factor-alpha business.industry Fatty liver NF-kappa B medicine.disease digestive system diseases Nicotinic agonist Endocrinology Liver Oncology biology.protein Molecular Medicine Steatohepatitis business medicine.drug |
| Zdroj: | Molecular Medicine Reports. 12:6925-6931 |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Non‑alcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease, affecting up to 30% of the general population worldwide. Non‑alcoholic steatohepatitis (NASH) is a severe form of NAFLD without any effective therapies available. The present study showed that activation of α7‑nicotinic acetylcholine receptor (α7 nAChR) may be a novel potential strategy for NASH therapy. Treatment with the α7 nAChR agonist nicotine for three weeks obviously attenuated hepatic steatosis in a high-fat diet‑induced mouse model of NASH. Investigation of the underlying mechanism showed that nicotine reduced the secretion of the pro‑inflammatory cytokines tumor necrosis factor α and interleukin 6 in vitro and in vivo. Inflammation is an integral part of NASH and is the most prevalent form of hepatic pathology found in the general population; therefore, the effect of α7 nAChR activation against NASH may be ascribed to its anti‑inflammatory effects. In addition, the present study showed that nicotine‑stimulated α7 nAChR activation led to a significant downregulation of nuclear factor kappa B (NK‑κB) and extracellular signal-regulated kinase (ERK). It therefore appeared that activation of α7 nAChR suppressed the production of pro‑inflammatory cytokines through NK‑κB and ERK pathways. In conclusion, the present study indicated that targeting α7 nAChR may represent a novel treatment strategy for NASH. |
| Databáze: | OpenAIRE |
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