CXCL10-induced IL-9 promotes liver fibrosis via Raf/MEK/ERK signaling pathway - 11/07/18
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Graphical abstract |
Highlights |
• | IL-9 expression is higher in liver cirrhosis tissues than normal liver tissues. |
• | The secretion of IL-9 in liver tissues was induced by CXCL10. |
• | Overexpression of IL-9 enhanced the severity of liver fibrosis. |
• | Raf/MEK/ERK signaling pathway was critical for IL-9-mediated liver fibrosis. |
Abstract |
Liver fibrosis is a typical complication of chronic liver diseases resulting in cirrhosis that remains a major public health problem. The aim of the present study was to identify the role of interleukin-9 (IL-9), an important regulator of inflammation and autoimmune diseases, in hepatic fibrosis progression. It was found that the expression of IL-9 was significantly increased in liver tissues of liver cirrhosis patients compared with that in healthy controls. Moreover, CXCL10, not CXCL9 or CXCL11, induced IL-9 expression in the liver tissue. Overexpression of IL-9 enhanced the severity of liver fibrosis in the carbon tetrachloride (CCl4)-induced liver fibrosis model. Western Blotting analysis revealed that this pro-fibrosis bioactivity of IL-9 was attributed to its selective activation of Raf/MEK/ERK signaling. Finally, administration of neutralizing anti-IL-9 antibody ameliorated liver fibrosis and attenuated the activation of hepatic stellate cells in mice. All these findings indicate that IL-9 plays a deleterious role in the development and progression of liver fibrosis, and IL-9 based immunotherapy may prove to be a promising strategy for the treatment of liver fibrosis.
Le texte complet de cet article est disponible en PDF.Keywords : Liver fibrosis, Interleukin-9, CXCL10, Raf/MEK/ERK
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Vol 105
P. 282-289 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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