Expression of cyclooxygenase 2 and cytosolic phospholipase A(2) in the liver tissue of patients with chronic hepatitis and liver cirrhosis

Hepatol Res. 2002 Jul;23(3):185-195. doi: 10.1016/s1386-6346(01)00177-2.


Cyclooxgenase (COX) and phospholipase A(2) (PLA(2)) are crucial rate-limiting enzymes involved in the conversion of arachidonic acid to prostaglandin H(2), the precursor of various compounds including prostaglandins (PGs), prostacyclin, and thromboxanes in the process of PGs' synthesis. Recent studies have shown increased levels of COX(2) in adjacent cirrhotic tissue of hepatocellular carcinoma. The relationship between the expression of COX(2) or cytosolicPLA(2) (cPLA(2)) and liver fibrosis has not been described previously. We used 45 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsies from patients with chronic hepatitis, consisting of 7 cases of F(0), 10 cases of F(1), 10 cases of F(2), 9 cases of F(3) and 9 cases of liver cirrhosis (LC) according to the New Inuyama Classification of the staging of liver fibrosis. The expression of COX(2) and cPLA(2) was investigated by immunohistochemistry, western blotting and image analysis. The positive signals for COX(2) and cPLA(2) were observed in the cytoplasm of hepatocytes. The signal intensity of COX(2) increased significantly with the progression of liver fibrosis (P<0.001) and no significant difference was observed in the relative amount of cPLA(2) from group F(0) to group LC. According to the New Inuyama Classification of hepatitis activity grading, 45 samples were classified as group A(1) (23 cases), group A(2) (19 cases) and group A(3) (3 cases). No significant differences were found in the relative amount of COX(2) and cPLA(2) between group A(1) and group A(2-3). Significant correlation was observed between the relative amount of COX(2) and hyaluronan (P<0.01). Our findings suggested that COX(2) may be involved in liver fibrogenesis.