Objective To investigate the expression levels of interleukin 25 (IL-25) and its related factors in the serum and liver of patients with non-alcoholic fatty liver disease (NAFLD) and explore the significance. Methods Between September 2017 and February 2019, NAFLD patients (n=50) who met the criteria of the disease and control patients (n=20) who undergoing partial hepatectomy due to hepatic hemangioma or hepatic cyst in the First Affiliated Hospital of Nanchang University were enrolled in this study. Serum levels of IL-25 and other cytokines were detected by ELISA. Then 6 patients in control group and 12 patients in NAFLD group were chosen to analyze hepatic mRNA expression levels of IL-25 and other cytokines by real-time fluorescent quantitative PCR, and protein levels of IL-25, CD68 (macrophage marker), CD206 (M2 macrophage marker) and glutaminase transaminase 2 (TGM2) by immunohistochemistry or immunofluorescence assay. Results ① Compared with the patients in control group, those of the NAFLD group had significantly reduced serum levels of IL-25 (P=0.003), IL-13 (P=0.007) and IL-4 (P=0.001). ② The mRNA levels of IL-13 (P=0.007) and IL-4 (P=0.003) in the liver of NAFLD patients were also obviously lower while that of CD68 (P < 0.001) was higher than those in the control group. ③ The NAFLD patients had more Küpffer cells (P < 0.001), fewer M2 macrophages (P < 0.001) and lower level of IL-25 (P < 0.001) in the liver than the patietns of the control group. With the aggravation of hepatic steatosis, the number of Küpffer cells was increased gradually (P < 0.001), while that of M2 macrophages (P < 0.001) and the level of IL-25 (P < 0.001) was decreased gradually. Conclusion The serum levels and liver contents of IL-25, Th2 type cytokine and intrahepatic M2 type macrophages are significantly reduced in the NAFLD patients, and these indicators are negatively correlated with the severity of liver steatosis.

Objective To observe and analyze the relationships among the level of interleukin 25 (IL-25), the stage of liver fibrosis and the polarization of hepatic M2 macrophages in patients with non-alcoholic fatty liver disease (NAFLD). Methods A total of 36 patients with NAFLD and 20 control patients were enrolled. Fibrotouch, HE staining, and immunohistochemistry were used to evaluate the stage of liver fibrosis. Patients with NAFLD were classified into groups of mild liver fibrosis (F1) (20 cases) and significant liver fibrosis (≥ F2) (16 cases). The level of serum IL-25 in each group was detected by ELISA. Real-time fluorescent quantitative PCR was used to detect the hepatic mRNA expression levels of IL-25, collagen1 (Col1), α mooth muscle actin (α-SMA), macrophage mannose receptor 1 (CD206/MR1) and transglutaminase 2 (TGM2). Immunohistochemistry was used to detect the protein levels of IL-25, α-SMA, CD206 and TGM2. Results There was no significant difference in the level of serum IL-25 among groups. Compared with patients in the control group and the mild liver fibrosis group, patients with significant liver fibrosis showed reduced mRNA expression levels of IL-25, CD206, and TGM2 in addition to lower levels of hepatic IL-25 protein and less polarization of M2 macrophages. Conclusion Down-regulation of IL-25 is accompanied by a decrease in the number of the M2 macrophages with the progression of liver fibrosis in NAFLD patients.

Interleukin (IL)-25 is a cytokine that has previously been shown to have a protective role against nonalcoholic fatty liver disease (NAFLD), which is associated with the induction of M2 macrophage differentiation. However, the direct relationships between IL-25 expression regulation, M2 induction and NAFLD remain unknown. In this study, we demonstrate that IL-25 promotes hepatic macrophage differentiation into M2a macrophages both in vivo and in vitro via the IL-13/STAT6 pathway. M2 macrophages that were differentiated in vitro were able to ameliorate high-fat diet HFD-induced hepatic steatosis. Furthermore, we found that IL-25 treatment, both in vitro and in vivo , promotes direct binding of STAT6 to the IL-25 gene promoter region. This binding of STAT6 in response to IL-25 treatment also resulted in the increase of IL-25 expression in hepatocytes. Together, these findings identify IL-25 as a protective factor against HFD-induced hepatic steatosis by inducing an increase of IL-25 expression in hepatocytes and through promotion of M2a macrophage production.

Interleukin (IL)‐25 is a cytokine that has previously been shown to have a protective role against nonalcoholic fatty liver disease (NAFLD), which is associated with the induction of M2 macrophage differentiation. However, the direct relationships between IL‐25 expression regulation, M2 induction and NAFLD remain unknown. In this study, we demonstrate that IL‐25 promotes hepatic macrophage differentiation into M2a macrophages both in vivo and in vitro via the IL‐13/STAT6 pathway. M2 macrophages that were differentiated in vitro were able to ameliorate high‐fat diet HFD‐induced hepatic steatosis. Furthermore, we found that IL‐25 treatment, both in vitro and in vivo, promotes direct binding of STAT6 to the IL‐25 gene promoter region. This binding of STAT6 in response to IL‐25 treatment also resulted in the increase of IL‐25 expression in hepatocytes. Together, these findings identify IL‐25 as a protective factor against HFD‐induced hepatic steatosis by inducing an increase of IL‐25 expression in hepatocytes and through promotion of M2a macrophage production.

白介素25(IL-25)是白介素17家族成员之一,在慢性炎性反应和肿瘤中具有重要作用.IL-25能够活化肝星状细胞并且可以诱导下游促纤维化细胞因子IL-4、IL-13的表达;IL-25可以促进M2型巨噬细胞极化并且可能会招募LY-6Clo单核细胞来源的巨噬细胞分化,而M2型巨噬细胞和LY-6Clo单核细胞来源的巨噬细胞都是抗肝纤维化细胞.IL-25及其相关因子与肝纤维化的关系还不甚清楚.