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

Dipeptidyl peptidase IV (DPP IV) is a cell surface ectoenzyme widely distributed in the rat body, present on the epithelial cells of the brush border membranes (e.g. bile canaliculi) and on the surface of reactive lymphocytes and fibroblasts. DPP IV has been implicated in hepatocyte-extracellular matrix interactions, fibroblast activation and proliferation and in T-cell activation. Aberrant DPP IV expression was found in human liver cirrhosis, and elevated serum DPP IV activity was reported in patients with primary biliary cirrhosis and chronic hepatitis C virus infection. The aim of the study was to examine serum DPP IV activity in experimental liver cirrhosis.

Liver cirrhosis was induced by administering diethyl-nitrosamine, phenobarbital and CCl4 in Fischer-344 male rats (n = 22). Phenobarbital-treated (n = 9) and nontreated (n = 9) male rats were used as controls. Serum DPP IV 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).

Significantly higher DPP IV activity was found in the sera of rats with experimental liver cirrhosis (39.2 +/- 3.7; mean +/- SD) compared to phenobarbital-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 and concentrations of aspartate aminotransferase (r = 0.73, P = 0.0001) and alanine aminotransferase (r = 0.69, P = 0.0004).

The significantly higher serum DPP IV activity found in experimental liver cirrhosis is in concordance with human observations. The elevation was probably not due to the enzyme induction effect of phenobarbital. In this experimental model, serum DPP IV seems to be an indicator for chronic liver injury.