Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease.
OBJECTIVE
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 alpha (TNFalpha) 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, TNFalpha, 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.
Malaguarnera
L
L
Department of Biomedical Sciences, University of Catania, Italy. lucmal@mbox.unict.it
Di Rosa
M
M
Zambito
A M
AM
dell'Ombra
N
N
Nicoletti
F
F
Malaguarnera
M
M
D000328:Adult; D000368:Aged; D018450:Disease Progression; D005234:Fatty Liver / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000378:metabolism; D015870:Gene Expression; D006596:Hexosaminidases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007728:Kupffer Cells / Q000201:enzymology* / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D005293:Ferritins; D006596:Hexosaminidases; C086400:chitotriosidase