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Thalidomide has been used to reduce liver inflammation and fibrosis in HCV\u2010infected patients, but its impact on HCV replication remains unclear. This study examined the effect of thalidomide on HCV replication in vitro. Results revealed that while thalidomide reduced IL\u20108 and nuclear factor kappa B (NF\u2010\u03baB) activity by 95% and 46% in Huh\u20107 cells, increasing concentrations of thalidomide correlated with a linear rise in HCV replication (17\u2010fold at 200\u2003\u03bc<jats:sc>m<\/jats:sc>). The NF\u2010\u03baB inhibitors, wedelolactone and NF\u2010\u03baB activation inhibitor\u20101, which mimic the actions of thalidomide by preventing phosphorylation and activation of I\u03baB kinase (IKK) and hence block NF\u2010\u03baB activity, increased HCV RNA by 18\u2010 and 19\u2010fold, respectively. During in vitro HCV replication in Huh\u20107 cells, we observed a 30% increase in IKK\u03b1 protein and 55% decrease in NF\u2010\u03baB(p65)\/RelA protein relative to cellular \u03b2\u2010actin. Ectopic expression of IKK\u03b1 to enhance the inactive form of IKK in cells undergoing virus replication led to a 13\u2010fold increase in HCV RNA. Conversely, enhanced expression of NF\u2010\u03baB(p65)\/RelA in infected cells resulted in a 17\u2010fold reduction in HCV RNA. In conclusion, HCV RNA replication was significantly augmented by the inhibition of IKK activation and subsequent NF\u2010\u03baB signalling, whereas a restoration of NF\u2010\u03baB activity by the addition of NF\u2010\u03baB\/RelA markedly reduced HCV replication. This study lends added importance to the role of the NF\u2010\u03baB signalling pathway in controlling HCV replication.<\/jats:p>","DOI":"10.1111\/j.1365-2893.2011.01505.x","type":"journal-article","created":{"date-parts":[[2011,8,16]],"date-time":"2011-08-16T14:36:39Z","timestamp":1313505399000},"source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of I\u03baB kinase by thalidomide increases hepatitis C virus RNA replication"],"prefix":"10.1111","volume":"19","author":[{"given":"E.","family":"Rance","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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