Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease

• Published in: Gut Vol. 55; no. 9; pp. 1313 - 1320
• Main Authors: Malaguarnera, L, Di Rosa, M, Zambito, A M, dell’Ombra, N, Nicoletti, F, Malaguarnera, M
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.09.2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Ac-LDL; acetyl lipoprotein; Adult; Aged; Alcohol; Biological and medical sciences; Biopsy; BMI; body mass index; Chemokines; Chit; chitotriosidase; Cytokines; Diabetes; Disease Progression; Enzymes; Fatty Liver - enzymology; Fatty Liver - metabolism; Female; Ferritins - metabolism; Gangrene; GAPDH; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal surgery; Gene Expression; glyceraldeyde-3-phosphate dehydrogenase; Hepatitis; Hexosaminidases - biosynthesis; Hexosaminidases - genetics; HSC; human hepatic stellate cell; Humans; Kupffer Cells - enzymology; Kupffer Cells - metabolism; Lipid Peroxidation; Lipids; Liver cirrhosis; Liver Disease; Liver diseases; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Metabolic disorders; Middle Aged; NASH; non-alcoholic steatohepatitis; O2; Other diseases. Semiology; Ox-LDL; Oxidative stress; oxidised low density lipoproteins; Patients; Polymerase Chain Reaction - methods; reactive oxygen species; RNA, Messenger - genetics; Rodents; ROS; simple steatosis; superoxide anion; Superoxides - metabolism; TNFα; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; tumour necrosis factor α; Human; Kupffer cell; Non alcoholic steatohepatitis; Gastroenterology; Digestive diseases; Hepatic disease; Gene expression
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gut.2005.075697

Background and aims: Non-alcoholic steatohepatitis (NASH) is a clinicopathological condition characterised by a necroinflammatory disorder with fatty infiltration of the hepatocytes. The molecular mechanisms involved in the anomalous behaviour of liver cells have only partially been determined. Human chitotriosidase (Chit) is a chitinolytic enzyme mainly produced by activated macrophages. The aim of this study was to investigate the expression of the chitinase-like gene in Kupffer cells, to determine how chitotriosidase may be implicated in the progression from uncomplicated steatosis to steatohepatitis with progressive fibrosis. Methods: 75 subjects were studied: 40 with NASH, 20 with simple steatosis, and 15 normal controls. Kupffer cells obtained from liver biopsies were used to detect CHIT expression, superoxide anion (O2−), lipid peroxidation, and tumour necrosis factor α (TNFα) and ferritin levels. Results: CHIT expression differed markedly in livers from normal controls and in those from patients with simple steatosis or non-alcoholic steatohepatitis. A significant correlation between mRNA CHIT and O2−, lipid peroxidation, TNFα, and ferritin levels was observed in both NASH and simple steatosis. Conclusions: Human Kupffer cells in NASH patients overproduce chitotriosidase. At the highest levels of production, this enzyme may play a role in increasing the risk for a poor outcome in steatohepatitis.