Non-alcoholic fatty liver disease(NAFLD)is characterized by a spectrum of hepatic diseases,including fatty liver,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.NAFLD is a hepatic manifestation of...Non-alcoholic fatty liver disease(NAFLD)is characterized by a spectrum of hepatic diseases,including fatty liver,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.NAFLD is a hepatic manifestation of metabolic syndrome and has become the leading cause of liver transplantation,necessitating an in-depth understanding of its underlying pathogenic mechanisms and the identification of viable drug targets.Although fatty liver is benign and does not exert marked liver damage or inflammation,NAFLD progression involves inflammatory processes facilitated by immune cells.Macrophages and monocytes constitute the pool of innate immune cells that contribute to NAFLD development in association with other cell types,such as neutrophils,T cells,and natural killer cells.The concept that macrophages contribute to the inflammatory processes in NAFLD development has long been debated;however,the remarkable advances in experimental techniques have rapidly uncovered new subpopulations of macrophages and monocytes,whose functions need to be comprehensively elucidated.The current review focuses on the recent expansion of our knowledge of the heterogeneous population of macrophages crucially involved in NAFLD development.In addition,the present paper discusses ongoing efforts to target macrophages and inflammatory processes to develop optimal therapeutic agents against non-alcoholic steatohepatitis.展开更多
Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver ...Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver injury,inflammatory cells,inflammatory mediators,cytokines,and the gut microbiome.In the current review,we discuss recent data on a large number of cytokines that play important roles in regulating liver injury,inflammation,fibrosis,and regeneration,with a focus on interferons and T helper(Th)1,Th2,Th9,Th17,interleukin(IL)-1 family,IL-6 family,and IL-20 family cytokines.Hepatocytes can also produce certain cytokines(such as IL-7,IL-11;and IL-33),and the functions of these cytokines in the liver are briefly summarized.Several cytokines have great therapeutic potential,and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases,which are also described.展开更多
基金supported by a 2-Year Research Grant of Pusan National University of Korea to S.Hwang.
文摘Non-alcoholic fatty liver disease(NAFLD)is characterized by a spectrum of hepatic diseases,including fatty liver,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.NAFLD is a hepatic manifestation of metabolic syndrome and has become the leading cause of liver transplantation,necessitating an in-depth understanding of its underlying pathogenic mechanisms and the identification of viable drug targets.Although fatty liver is benign and does not exert marked liver damage or inflammation,NAFLD progression involves inflammatory processes facilitated by immune cells.Macrophages and monocytes constitute the pool of innate immune cells that contribute to NAFLD development in association with other cell types,such as neutrophils,T cells,and natural killer cells.The concept that macrophages contribute to the inflammatory processes in NAFLD development has long been debated;however,the remarkable advances in experimental techniques have rapidly uncovered new subpopulations of macrophages and monocytes,whose functions need to be comprehensively elucidated.The current review focuses on the recent expansion of our knowledge of the heterogeneous population of macrophages crucially involved in NAFLD development.In addition,the present paper discusses ongoing efforts to target macrophages and inflammatory processes to develop optimal therapeutic agents against non-alcoholic steatohepatitis.
基金supported by the intramural program of the NIAAA(Bin Gao),U01 AA022614,and R01 DK099205(Tatiana Kisseleva)and AA011576 and AA017729(Gyongyi Szabo).
文摘Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver injury,inflammatory cells,inflammatory mediators,cytokines,and the gut microbiome.In the current review,we discuss recent data on a large number of cytokines that play important roles in regulating liver injury,inflammation,fibrosis,and regeneration,with a focus on interferons and T helper(Th)1,Th2,Th9,Th17,interleukin(IL)-1 family,IL-6 family,and IL-20 family cytokines.Hepatocytes can also produce certain cytokines(such as IL-7,IL-11;and IL-33),and the functions of these cytokines in the liver are briefly summarized.Several cytokines have great therapeutic potential,and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases,which are also described.
