Neutrophils in MASLD and MASH

초록

Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD)and its progressive form, Metabolic Dysfunction Associated Steatohepatitis(MASH), represent significant health concerns associatedwith the metabolic syndrome. These conditions are characterizedby excessive hepatic fat accumulation, inflammation,and potential progression to cirrhosis and hepatocellular carcinoma. Neutrophils are innate immune cells that play a pivotalrole in the development of MASLD and MASH. They can infiltratethe hepatic microenvironment in response to inflammatorycytokines and damage associated molecular patterns (DAMPs)derived from the liver and exacerbate tissue damage by releasingof reactive oxygen species (ROS), cytokines, and neutrophil extracellulartraps (NETs). Moreover, neutrophils can disrupt the metabolismof hepatocytes through key factors such as neutrophilelastase (NE) and human neutrophil peptides-1 (HNP-1), leadingto inflammation and fibrosis, while myeloperoxidase (MPO) andlipocalin (LCN2) are involved in inflammatory and fibroticprocesses. In contrast, neutrophils contribute to liver protectionand repair through mechanisms involving microRNA-223 andmatrix metalloproteinase 9 (MMP9). This dual role of neutrophilshighlights their significance in the pathogenesis of MASLD andMASH. This review summarizes current understanding fromrecent studies on the involvement of neutrophils in MASLD andMASH. Understanding complex roles of neutrophils within theliver’s unique microenvironment offers insights into novel therapeuticstrategies, emphasizing the need for further research toexplore neutrophil-targeted interventions for managing MASLDand MASH.

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