Adenovirus-mediated viral interleukin-10 gene transfer prevents concanavalin A-induced liver injury
| Autor: | Yan-Fei Xie, Qing-Xia Niu, Yan-Chun Zhou, Sui Chen, Jun-Jun Cao, Shao-Ying Chen |
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| Rok vydání: | 2012 |
| Předmět: |
T-Lymphocytes
medicine.medical_treatment T cell Genetic Vectors Down-Regulation Biology Monocytes Adenoviridae Viral vector Proinflammatory cytokine Interferon-gamma Mice Immune system Concanavalin A medicine Animals Aspartate Aminotransferases Liver injury Hepatology Gene Transfer Techniques Gastroenterology Alanine Transaminase Liver Failure Acute medicine.disease Molecular biology Interleukin-10 Mice Inbred C57BL Interleukin 10 Cytokine medicine.anatomical_structure Liver biology.protein Interleukin-4 Mitogens |
| Zdroj: | Digestive and Liver Disease. 44:398-405 |
| ISSN: | 1590-8658 |
| DOI: | 10.1016/j.dld.2011.11.013 |
| Popis: | Background and aim Liver injury is closely associated with immune inflammation. Lacking immunostimulatory functions, viral interleukin-10 (vIL-10), a cellular IL-10 homologue, has been an attractive molecule for immunomodulatory therapy. We aimed to reveal a protective effect of the gene transfer of an adenoviral vector encoding vIL-10 on liver injury induced by concanavalin A. Methods C57BL/6J mice were intravenously injected with adenoviral vector encoding vIL-10 before concanavalin A challenge. Liver injury was assessed. Interferon-γ and interleukin-4 levels were measured by ELISA. The activation of splenic and hepatic immune cells was analysed using an MTT assay. Results Adenoviral vector encoding vIL-10 pretreatment significantly decreased concanavalin A-mediated elevations in serum alanine aminotransaminase and aspartate aminotransaminase activity, and necrotic area in liver tissues. The protective effect of adenoviral vector encoding vIL-10 was attributed to its inhibition of T cell activation, and production of interferon-γ and interleukin-4 by the immune cells. Recombinant mouse IL-10, a high homologous cytokine to vIL-10, effectively downregulated interferon-γ and interleukin-4 release by hepatic mononuclear cells. Conclusion Adenovirus vector-mediated vIL-10 gene transfer can prevent concanavalin A-induced hepatic injury, minimise pro-inflammatory cytokine release, and inhibit the activation of T lymphocytes. |
| Databáze: | OpenAIRE |
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