Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease
- 1Department of Biomedical Sciences, University of Catania, Catania, Italy
- 2Department of Senescence, Urological and Neurological Sciences, University of Catania
- 3Department of Pathology and Experimental Clinical Medicine, University of Udine, Udine, Italy
- Correspondence to:
Professor Lucia Malaguarnera
Via E De Amicis 24, 95039 Trecastagni, Catania, Italy;
- Received 10 February 2006
- Accepted 21 February 2006
- Published Online First 6 July 2006
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.
- Ac-LDL, acetyl lipoprotein
- BMI, body mass index
- Chit, chitotriosidase
- GAPDH, glyceraldeyde-3-phosphate dehydrogenase
- HSC, human hepatic stellate cell
- NASH, non-alcoholic steatohepatitis
- Ox-LDL, oxidised low density lipoproteins
- O2−, superoxide anion
- ROS, reactive oxygen species
- TNFα, tumour necrosis factor α
Conflict of interest: None declared.