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

Abstract

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.

Assessment of Cox2 and CMV in patients with chronic HCV infection

“…Cheng and Hada 27 was proved that up-regulation of COX-2 expression was present in cirrhotic tissues relative to HCC as well as in well-differentiated HCC. over-expression of COX-2 in cirrhosis was apparent in a study that assess in patients with cirrhosis due to HBV and HCV infection while our series inclusive HCV infection patients Mohamed et al 28 Another study, we were able to express a significant relation found between overall COX-2 expression and viral load of the HCV-RNA. 29 while Waris and Siddiqui 30 was found the increase in Cox-2 mRNA expression in cells containing the HCV replicon, indicate that HCV gene expression control Cox-2 activity at the stage of transcription.…”

HBx targeting to mitochondria and ROS generation are necessary but insufficient for HBV-induced cyclooxygenase-2 expression

“…The COX-2 expression triggers the conversion of arachidonic acid to prostanoids, initiating many of the prostanoid-mediated pathological aspects of inflammation [14]. Significantly, increased expression of COX-2 has been documented in cirrhotic livers from patients with HCV or HBV infections [15] and in various cancers [4]. In cirrhotic livers, COX-2 expression has been shown to increase significantly with inflammation and the progression of liver fibrosis, suggesting a role for COX-2 as a mediator of the transition from inflammation to cancer [15,16].…”

“…Significantly, increased expression of COX-2 has been documented in cirrhotic livers from patients with HCV or HBV infections [15] and in various cancers [4]. In cirrhotic livers, COX-2 expression has been shown to increase significantly with inflammation and the progression of liver fibrosis, suggesting a role for COX-2 as a mediator of the transition from inflammation to cancer [15,16]. Furthermore, a study demonstrated that HBx-induced COX-2 expression contributes to tumor cell invasion [17].…”

Hepatitis B Virus Induces a Novel Inflammation Network Involving Three Inflammatory Factors, IL-29, IL-8, and Cyclooxygenase-2

“…Accumulated evidence has shown that viral proteins can stimulate COX-2 expression; for example, latent membrane protein 1 of the EBV (17), core and NS5A proteins of HCV (18), and HBx (19). COX-2 is overexpressed in liver cirrhosis, contributing to PG overproduction, which may be a major component of the inflammation and hyperdynamic circulation associated with HCC development in cirrhosis (20). Moreover, COX-2 and its downstream PG receptor EP1-mediated signaling pathway accelerate LPS-induced liver injury (21).…”