Interleukin-17-mediated inflammation promotes nonalcoholic fatty liver disease in mice with regulation of M1-type macrophage polarization
10.3760/cma.j.issn.1007-3418.2018.12.008
- VernacularTitle: 白细胞介素17通过促进巨噬细胞M1型极化调控小鼠非酒精性脂肪性肝病组织炎症反应的机制
- Author:
Yi YANG
1
;
Chenyang HAN
;
Qiaobing GUAN
;
Shuiliang RUAN
Author Information
1. Jiaxing Second Hospital, Jiaxing Zhejiang 314001, China
- Publication Type:Journal Article
- Keywords:
Interleukin 17;
Nonalcoholic fatty liver;
Macrophages;
Inflammatory reaction
- From:
Chinese Journal of Hepatology
2018;26(12):916-921
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the mechanism of interleukin (IL)-17 in mice with non-alcoholic fatty liver disease for promoting M1-type macrophage polarization to exacerbate liver inflammation, and to provide references for the mechanism of NAFLD occurrence and development.
Methods:A mouse model of NAFLD was constructed by high-fat diet. Mice were divided into control group, model group, IL-17 group, and anti IL-17 group. Histopathological changes of the liver were observed by HE staining. The serum levels of ALT and AST in peripheral blood of mice was detected by chemical colorimetry. Macrophages labeled with F4/80-PE, CD11C-FITC was designated as M1-type macrophages, those labeled with F4/80-PE, and CD206-APC was designated as M2-type macrophages. The proportion of M1 and M2 macrophages infiltrated into the liver tissues of mice were measured by flow cytometry. CD168 expression level of liver tissues was detected using immunohistochemistry. Protein and mRNA levels of the marker molecules (iNOS, TNF-alpha and IL-6) of M1 macrophages were detected using ELISA and RT-Q PCR. Western blot was used to detect the protein expression of JAK-STAT signal pathway and the expression level of MCP-1. Data were analyzed using one-way ANOVA and t-test.
Results:High-fat diet NAFLD mice model was successfully constructed. IL-17 had increased the proportion of M1 macrophages in mice liver tissues and decreased the proportion of M2 macrophages (P < 0.05). The proportion of M1 and M2 macrophages in the liver tissues of normal mice was 7.9% ± 1.1% and 19.2% ± 1.8%. The proportion of M1 and M2 macrophages in the model group was 17.3% ± 2.5% and 15.0% ± 2.1. The proportion of M1 macrophages (33.8% ± 4.2%) in IL-17 group was higher than model group, while the proportion of M2 macrophages (7.8% + 1.0%) in IL-17 group was lower than model group. Protein and mRNA marker levels of M1 macrophage (iNOS, IL-12, TNFα and IL-6) in liver tissues were significantly higher than model group, control group, and anti-IL-17 group (P < 0.05). The expression levels of JAK1, STAT1, MCP-1, and CD168 in mice liver tissues of IL-17 group had increased (P < 0.05). The levels of aspartate and alanine aminotransferases in peripheral blood of mice in IL-17 group were significantly higher than other three groups (P < 0.05).
Conclusion:IL-17 can promote M1-type macrophage polarization, and exacerbates the liver inflammatory response to accelerate the progression of NAFLD in mice.
