Iron-accumulating splenocytes may exacerbate non-alcoholic steatohepatitis through the production of proinflammatory cytokines and reactive oxygen species
Iron-accumulating splenocytes may exacerbate non-alcoholic steatohepatitis through the production of proinflammatory cytokines and reactive oxygen species
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DOI：
10.1177/15353702221077218
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发表时间：
2022-02
影响因子：
3.2
通讯作者：
K. Murotomi;Hirosuke Tawara;M. Sutoh;M. Yasunaga
中科院分区：
文献类型：
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作者：
K. Murotomi;Hirosuke Tawara;M. Sutoh;M. Yasunaga
非酒精性脂肪性肝炎（NASH）由非酒精性脂肪性肝病（NAFLD）通过多个平行事件引起，包括肝脏甘油三酯蓄积、氧化应激和炎症。肝脏和多个其他器官之间的复杂相互作用参与NASH的发展。尽管脾源性体液因子可直接促进通过门静脉的NAFLD/NASH发作，但脾脏在NASH早期阶段的状态仍然未知。在这里，我们的目的是调查脾细胞是否可能通过产生活性氧（ROS）和促炎细胞因子来加剧NASH。Tsumura Suzuki肥胖型糖尿病（TSOD）小鼠的脾脏中观察到铁蓄积，但肝脏中未观察到铁蓄积，并且脾脏中吞噬巨噬细胞的比例增加，显示出NASH早期的组织学特征。脾细胞产生中等量的ROS，并释放大量的肿瘤坏死因子（TNF）-α，以响应脂多糖，表明铁积累脾中活化的巨噬细胞释放过量的炎症细胞因子。我们的研究结果表明，铁积累的脾细胞可以很容易地诱导炎症，并有助于通过门静脉加重NASH。因此，在开发针对NASH的新治疗靶点时应考虑脾脏中铁代谢的调节。
Non-alcoholic steatohepatitis (NASH) results from non-alcoholic fatty liver disease (NAFLD) via multiple-parallel events, including hepatic triglyceride accumulation, oxidative stress, and inflammation. The complex interaction between the liver and multiple other organs is involved in NASH development. Although spleen-derived humoral factors can directly contribute to NAFLD/NASH onset via the portal vein, the status of the spleen in the early stage of NASH remains unknown. Here, our aim was to investigate whether splenocytes may exacerbate NASH via the generations of reactive oxygen species (ROS) and proinflammatory cytokines. Iron accumulation was observed in the spleen but not the liver, and the proportion of phagocytic macrophages increased in the spleen of Tsumura Suzuki Obese Diabetes (TSOD) mice showing histological characteristics of NASH in the early stage. The splenocytes generated moderate amounts of ROS and released high amounts of tumor necrosis factor (TNF)-α in response to lipopolysaccharide, indicating excessive inflammatory cytokine released by activated macrophages in iron-accumulating spleens. Our results suggest that iron-accumulating splenocytes can easily induce inflammation and contribute to exacerbate NASH via the portal vein. Thus, the regulation of iron metabolism in the spleen should be considered in the development of novel therapeutic targets against NASH.