Source:http://linkedlifedata.com/resource/pubmed/id/21444704
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2011-5-19
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pubmed:abstractText |
A lack of patient response to alpha interferon (?-IFN) plus ribavirin (RBV) treatment is a major problem in eliminating hepatitis C virus (HCV). We screened chemical libraries for compounds that enhanced cellular responses to ?-IFN and identified a triterpenoid, toosendanin (TSN). Here, we studied the effects and mechanisms of action of TSN on HCV replication and its effect on ?-IFN signaling. We treated HCV genotype 1b replicon-expressing cells and HCV-J6/JFH-infected cells with TSN, with or without ?-IFN, and the level of HCV replication was quantified. To study the effects of TSN on ?-IFN signaling, we detected components of the interferon-stimulated gene factor 3 (ISGF3), phosphorylated signal transducer and activator of transcription 1 (STAT1), and STAT2 by Western blotting analysis; expression levels of mRNA of interferon regulatory factor 9 using real-time reverse transcription-PCR (RT-PCR); and interferon-stimulated response element reporter activity and measured the expression levels of interferon-inducible genes for 2',5'-oligoadenylate synthetase, MxA, protein kinase R, and p56 using real-time RT-PCR. TSN alone specifically inhibited expression of the HCV replicon (50% effective concentration = 20.6 nM, 50% cytotoxic concentration > 3 ?M, selectivity index > 146). Pretreatment with TSN prior to ?-IFN treatment was more effective in suppressing HCV replication than treatment with either drug alone. Although TSN alone did not activate the ?-IFN pathway, it significantly enhanced the ?-IFN-induced increase of phosphorylated STATs, interferon-stimulated response element activation, and interferon-stimulated gene expression. TSN significantly increased baseline expression of interferon regulatory factor 9, a component of interferon-stimulated gene factor 3. Antiviral effects of treatment with ?-IFN can be enhanced by pretreatment with TSN. Its mechanisms of action could potentially be important to identify novel molecular targets to treat HCV infection.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Drugs, Chinese Herbal,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/toosendanin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1098-6596
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pubmed:author |
pubmed-author:AzumaSeishinS,
pubmed-author:FunaokaYusukeY,
pubmed-author:ItsuiYasuhiroY,
pubmed-author:KakinumaSeiS,
pubmed-author:KitazumeAkikoA,
pubmed-author:KiyohashiKeiK,
pubmed-author:MurakawaMiyakoM,
pubmed-author:NakagawaMinaM,
pubmed-author:Nishimura-SakuraiYukiY,
pubmed-author:NittaSayuriS,
pubmed-author:OookaShinyaS,
pubmed-author:SakamotoNaoyaN,
pubmed-author:TsuchiyaKiichiroK,
pubmed-author:UeyamaMayumiM,
pubmed-author:WatanabeMamoruM,
pubmed-author:WatanabeTakakoT
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pubmed:issnType |
Electronic
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pubmed:volume |
55
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2537-45
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pubmed:meshHeading |
pubmed-meshheading:21444704-Antiviral Agents,
pubmed-meshheading:21444704-Cell Line, Tumor,
pubmed-meshheading:21444704-Drug Therapy, Combination,
pubmed-meshheading:21444704-Drugs, Chinese Herbal,
pubmed-meshheading:21444704-Hepacivirus,
pubmed-meshheading:21444704-Hepatitis C,
pubmed-meshheading:21444704-Humans,
pubmed-meshheading:21444704-Interferon-alpha,
pubmed-meshheading:21444704-RNA, Viral,
pubmed-meshheading:21444704-Virus Replication
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pubmed:year |
2011
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pubmed:articleTitle |
Inhibitory effect of a triterpenoid compound, with or without alpha interferon, on hepatitis C virus infection.
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pubmed:affiliation |
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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