College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, South Korea.
Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, United States.
Front Endocrinol (Lausanne). 2021 Oct 11;12:751802. doi: 10.3389/fendo.2021.751802. eCollection 2021.
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of liver disorders, from fatty liver to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Compared with fatty liver, NASH is characterized by increased liver injury and inflammation, in which liver-infiltrating immune cells, with neutrophil infiltration as a hallmark of NASH, play a critical role in promoting the progression of fatty liver to NASH. Neutrophils are the first responders to injury and infection in various tissues, establishing the first line of defense through multiple mechanisms such as phagocytosis, cytokine secretion, reactive oxygen species production, and neutrophil extracellular trap formation; however, their roles in the pathogenesis of NASH remain obscure. The current review summarizes the roles of neutrophils that facilitate the progression of fatty liver to NASH and their involvement in inflammation resolution during NASH pathogenesis. The notion that neutrophils are potential therapeutic targets for the treatment of NASH is also discussed.
非酒精性脂肪性肝病（NAFLD）包括一系列肝脏疾病，从脂肪肝到非酒精性脂肪性肝炎（NASH）、肝硬化和肝细胞癌。与脂肪肝相比，NASH的特征是肝损伤和炎症增加，其中浸润肝脏的免疫细胞，以中性粒细胞浸润为 NASH 的标志，在促进脂肪肝向 NASH 的进展中起关键作用。中性粒细胞是各种组织损伤和感染的第一反应者，通过吞噬作用、细胞因子分泌、活性氧物质产生和中性粒细胞胞外陷阱形成等多种机制建立第一道防线；然而，它们在 NASH 发病机制中的作用仍不清楚。本综述总结了中性粒细胞在促进脂肪肝向 NASH 进展中的作用及其在 NASH 发病过程中炎症消退中的作用。还讨论了中性粒细胞作为治疗 NASH 的潜在治疗靶点的概念。
