Liver international : official journal of the International Association for the Study of the Liver · 2025
IL-25 Improves MAFLD by Suppressing the Notch Signalling in Hepatic Macrophages.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zheng Xuelian, Hu Dandan, Zhang Dongjing, Chen Ye, Wei Jianrui, Xie Bo, Wang Anjiang
Аннотация
BACKGROUND AND AIMS: Hepatic steatosis is characterised by hepatic lipid accumulation, inflammation and fibrosis, with macrophage polarisation playing a central role in disease progression. This study investigates the role of interleukin-25 (IL-25) in modulating macrophage polarisation and Notch signalling in a methionine-choline-deficient (MCD) diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) model.
METHODS: C57BL/6 mice were fed a MCD diet to induce MAFLD. Human hepatocytes and primary hepatic macrophages were treated with palmitic acid and/or IL-25. Methods included RT-qPCR, ELISA, Western blot and immunofluorescence for gene/protein expression. ChIP and luciferase assays were used to analyse STAT3/Notch-1 signalling.
RESULTS: We found that IL-25 expression was significantly downregulated in the livers of MCD-fed mice and in palmitic acid-treated hepatocytes. IL-25 treatment promoted M2 macrophage polarisation, evidenced by increased expression of Arg1, Chi3l3 and anti-inflammatory cytokines (IL-10, TGF-β), while suppressing pro-inflammatory cytokines (TNF-α, IL-6). Mechanistically, IL-25 inhibited the STAT3/Notch-1 pathway and induced IL-33, which negatively regulated the NF-κB/Jagged-1 axis, preventing M1 macrophage polarisation. Adoptive transfer of IL-25-induced M2a macrophages ameliorated hepatic steatosis and reduced ductular reaction in MCD-fed mice.
CONCLUSIONS: These findings suggest a role for IL-25 in modulating macrophage polarisation and inflammation in metabolic dysfunction-associated fatty liver disease, supporting its further exploration as a potential therapeutic strategy for inflammatory liver diseases.
METHODS: C57BL/6 mice were fed a MCD diet to induce MAFLD. Human hepatocytes and primary hepatic macrophages were treated with palmitic acid and/or IL-25. Methods included RT-qPCR, ELISA, Western blot and immunofluorescence for gene/protein expression. ChIP and luciferase assays were used to analyse STAT3/Notch-1 signalling.
RESULTS: We found that IL-25 expression was significantly downregulated in the livers of MCD-fed mice and in palmitic acid-treated hepatocytes. IL-25 treatment promoted M2 macrophage polarisation, evidenced by increased expression of Arg1, Chi3l3 and anti-inflammatory cytokines (IL-10, TGF-β), while suppressing pro-inflammatory cytokines (TNF-α, IL-6). Mechanistically, IL-25 inhibited the STAT3/Notch-1 pathway and induced IL-33, which negatively regulated the NF-κB/Jagged-1 axis, preventing M1 macrophage polarisation. Adoptive transfer of IL-25-induced M2a macrophages ameliorated hepatic steatosis and reduced ductular reaction in MCD-fed mice.
CONCLUSIONS: These findings suggest a role for IL-25 in modulating macrophage polarisation and inflammation in metabolic dysfunction-associated fatty liver disease, supporting its further exploration as a potential therapeutic strategy for inflammatory liver diseases.