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NS3 protein of hepatitis C virus regulates cyclooxygenase-2 expression through multiple signaling pathways.

Abstract：

:Hepatitis C virus (HCV) causes chronic hepatitis, which often results in the development of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. In this study, we demonstrated that the non-structural protein NS3 of HCV enhances cyclooxygenase-2 (COX-2) gene promoter activity, COX-2 mRNA expression, COX-2 protein production, and prostaglandin E2 (PGE2) release in HepG2 cells in a concentration-dependent fashion. We also showed that transcription factor NF-kappaB is required for the activation of COX-2 regulated by NS3. In addition, multiple signaling pathways are involved cooperatively in the expression of COX-2 activated by the viral protein in a calcium-independent manner, which requires signaling components including JNK, ERK, and PKD2. A thorough investigation of mechanism involved in the activation of COX-2 regulated by HCV would provide insights into our understanding the processes of liver inflammatory response and hepatocellular carcinoma development caused by the viral infection and also into the development of novel therapeutics against HCV infection.

journal_name

Virology

journal_title

Virology

authors

Lu L,Wei L,Peng G,Mu Y,Wu K,Kang L,Yan X,Zhu Y,Wu J

doi

10.1016/j.virol.2007.09.025

subject

Has Abstract

pub_date

2008-02-05 00:00:00

pages

61-70

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(07)00592-2

journal_volume

371

pub_type

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