Elevated serum dipeptidyl peptidase IV (CD26, EC 3.4.14.5) activity in experimental liver cirrhosis

Background Dipeptidyl peptidase IV (DPP IV) is a cell surface ectoenzyme wi dely distributed in the rat body, present on the epithelial cells of the br ush border membranes (e.g, bile canaliculi) and on the surface of reactive lymphocytes and fibroblasts. DPP TV has been implicated in hepatocyte-extra cellular matrix interactions, fibroblast activation and proliferation and i n T-cell activation. Aberrant DPP IV expression was found in human liver ci rrhosis, and elevated serum DPP IV activity was reported in patients with p rimary biliary cirrhosis and chronic hepatitis C virus infection. The aim o f the study was to examine serum DPP IV activity in experimental liver cirr hosis. Methods Liver cirrhosis was induced by administering diethyl-nitrosamine, p henobarbital and CCl4 in Fischer-344 male rats (n = 22). Phenobarbital-trea ted (n = 9) and nontreated (n = 9) male rats were used as controls. Serum D PP TV activity was measured using a microplate-based continuous-monitoring assay. Recombinant rat DPP IV was used as standard and Gly-Pro-PNA was used as substrate. Enzyme activity was given in nmol mL(-1) min(-1) (U L-1). Results Significantly higher DPP IV activity was found in the sera of rats with experimental liver cirrhosis (39.2 +/- 3.7; mean+/-SD) compared to phe nobarbital-treated (11 +/- 4, P<0.000002) and nontreated (10.9 +/- 0.9, P< 0.000002) rats. There was a positive correlation between DPP IV activity an d concentrations of aspartate aminotransferase (r = 0.73, P = 0.0001) and a lanine aminotransferase (r = 0.69, P = 0.0004). Conclusions The significantly higher serum DPP IV activity found in experim ental liver cirrhosis is in concordance with human observations. The elevat ion was probably not due to the enzyme induction effect of phenobarbital. I n this experimental model, serum DPP IV seems to be an indicator for chroni c liver injury.