ORIGINAL ARTICLE

Distribution of constitutive (COX-1) and inducible (COX-2) cyclooxygenase in postviral human liver cirrhosis: a possible role for COX-2 in the pathogenesis of liver cirrhosis

N A Mohammed¹, S A El-Aleem², H A El-Hafiz¹, R F T McMahon³

¹ Departments of Tropical Medicine and General Medicine, Minia University, Minia, Egypt
² Department of Physiology, University of Bristol, University Walk, Bristol BS8 1TD, UK
³ Laboratory Medicine Academic Group, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK

Correspondence to:
Correspondence to:
R F T McMahon
Laboratory Medicine Academic Group, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK and Department of Histopathology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK; ray.mcmahon{at}man.ac.uk

Aims: Prostaglandins produced by the action of cyclooxygenases (COX) are important mediators of systemic vasodilatation and inflammation in liver cirrhosis. The aim of this study was to investigate the distribution of COX-1 and COX–2 in postviral cirrhosis.

Methods: The immunohistochemical expression of the constitutive (COX-1) and the inducible (COX-2) isoenzymes was investigated in 15 patients with cirrhosis after hepatitis B and C infection; three normal control livers were also analysed.

Results: COX-2 was absent from normal liver but was highly expressed in cirrhosis, mainly in the inflammatory, sinusoidal, vascular endothelial, and biliary epithelial cells. Low amounts of COX-1 were expressed in both normal and cirrhotic livers, exclusively in sinusoidal and vascular endothelial cells, with no differences seen between normal and cirrhotic livers.

Conclusions: COX-2 is overexpressed in liver cirrhosis, and possibly contributes to prostaglandin overproduction, which may be a major component of the inflammation and hyperdynamic circulation associated with cirrhosis. Because COX-2 is thought to contribute to tumour development, high COX-2 production could be a contributor to hepatocellular carcinoma development in cirrhosis. The finding of COX-2 and not COX-1 upregulation in cirrhosis could provide a possible new role for selective COX-2 inhibitors in reducing inflammation and minimising the occurrence of hepatocellular carcinoma in patients with cirrhosis.

Keywords: liver cirrhosis; viral hepatitis; portal hypertension; prostaglandins; cyclooxygenase

Abbreviations: COX, cyclooxygenases; HCC, hepatocellular carcinoma; NSAID, non-steroidal anti-inflammatory drug; PG, prostaglandin; TBS, Tris buffered saline

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