title: Pathophysiological mechanisms and therapeutic potentials of macrophages in non-alcoholic steatohepatitis.
abstract: BACKGROUND
  Non-alcoholic steatohepatitis (NASH), a hepatic manifestation of metabolic syndrome, is a major cause of morbidity and healthcare burden worldwide. While the molecular pathogenesis of NASH remains unclear and therapeutic options are limited, inflammation is recognized as an essential factor for NASH development. Factors that link NASH to inflammation are macrophages and their secreted cytokines.
  
  
  METHODS
  This review summarizes the current knowledge of macrophage-mediated molecular pathways in NASH to shed insights on potential pharmacotherapeutic applications.
  
  
  CONCLUSIONS
  Macrophages are not only known for their role of phagocytosis in innate immunity, but also for both extrinsic and intrinsic regulation of inflammatory functions of many cytokines. Recent advances have revealed the effects of macrophage recruitment and polarization on the development of NASH. We and others have shown that the proliferation of hepatic macrophages and the subsequent production of pro-inflammatory cytokines initiates inflammatory cascades, orchestrates activities of transcription factors involved in lipid metabolism/translocation, and modulates programmed cell death. Together, these findings support the pathophysiological role of macrophages in the pathogenesis of NASH. Thus, evaluating potential therapeutic targets against the infiltration and/or polarization of specific macrophage subtypes is of clinical interest for alleviation of early-stage NASH, with the goal of halting disease progression.
authors.affiliation: a Institute of Digestive Disease and the Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences , CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong , Shatin , Hong Kong.
authors.forename: Ruonan
authors.initials: R
authors.lastname: Wu
authors.affiliation: a Institute of Digestive Disease and the Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences , CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong , Shatin , Hong Kong.
authors.forename: Geicho
authors.initials: G
authors.lastname: Nakatsu
authors.affiliation: a Institute of Digestive Disease and the Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences , CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong , Shatin , Hong Kong.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Institute of Digestive Disease and the Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences , CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong , Shatin , Hong Kong.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D006801:Humans; D007501:Iron / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*
chemical_list: D007501:Iron
keywords: Macrophage; autophagy; inflammation; lipid metabolism; oxidative stress