DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Dong Eon | ko |
dc.contributor.author | Jang, Mi-Jin | ko |
dc.contributor.author | Kim, Young Ran | ko |
dc.contributor.author | Lee, Joo-Young | ko |
dc.contributor.author | Cho, Eun Byul | ko |
dc.contributor.author | Kim, Eunha | ko |
dc.contributor.author | Kim, Ye Ji | ko |
dc.contributor.author | Kim, Mi Young | ko |
dc.contributor.author | Jeong, Won-Il | ko |
dc.contributor.author | Kim, Seyun | ko |
dc.contributor.author | Han, Yong-Mahn | ko |
dc.contributor.author | Lee, Seung-Hyo | ko |
dc.date.accessioned | 2017-09-08T06:01:18Z | - |
dc.date.available | 2017-09-08T06:01:18Z | - |
dc.date.created | 2017-07-04 | - |
dc.date.created | 2017-07-04 | - |
dc.date.created | 2017-07-04 | - |
dc.date.issued | 2017-07 | - |
dc.identifier.citation | TOXICOLOGY, v.387, pp.1 - 9 | - |
dc.identifier.issn | 0300-483X | - |
dc.identifier.uri | http://hdl.handle.net/10203/225839 | - |
dc.description.abstract | Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events. Treatment with acetaminophen significantly elevated the levels of inflammatory cytokines by hES-HLCs. Moreover, three human immune cell lines, Jurkat, THP-1, and NK92MI, were activated when cultured in conditioned medium obtained from acetaminophen-treated hES-HLCs. To further validate, we tested thiazolidinedione (TZD) class, antidiabetic drugs, including troglitazone withdrawn from the market because of severe idiosyncratic drug hepatotoxicity. We found that TZD drug treatment to hES-HLCs resulted in the production of pro-inflammatory cytokines and eventually associated immune cell activation. In summary, our study demonstrates for the first time the potential of hES-HLCs as an in vitro model system for assessment of drug-induced as well as immune-mediated hepatotoxicity. | - |
dc.language | English | - |
dc.publisher | ELSEVIER IRELAND LTD | - |
dc.title | Prediction of drug-induced immune-mediated hepatotoxicity using hepatocyte-like cells derived from human embryonic stem cells | - |
dc.type | Article | - |
dc.identifier.wosid | 000408072000001 | - |
dc.identifier.scopusid | 2-s2.0-85021161095 | - |
dc.type.rims | ART | - |
dc.citation.volume | 387 | - |
dc.citation.beginningpage | 1 | - |
dc.citation.endingpage | 9 | - |
dc.citation.publicationname | TOXICOLOGY | - |
dc.identifier.doi | 10.1016/j.tox.2017.06.005 | - |
dc.contributor.localauthor | Kim, Mi Young | - |
dc.contributor.localauthor | Jeong, Won-Il | - |
dc.contributor.localauthor | Kim, Seyun | - |
dc.contributor.localauthor | Han, Yong-Mahn | - |
dc.contributor.localauthor | Lee, Seung-Hyo | - |
dc.contributor.nonIdAuthor | Jang, Mi-Jin | - |
dc.contributor.nonIdAuthor | Kim, Young Ran | - |
dc.contributor.nonIdAuthor | Lee, Joo-Young | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Drug-induced liver injury | - |
dc.subject.keywordAuthor | Hepatocyte-kike cells derived from human | - |
dc.subject.keywordAuthor | embryonic stem cells | - |
dc.subject.keywordAuthor | Immune cells. drug screening system | - |
dc.subject.keywordAuthor | Pro- and anti- inflammatory cytokines | - |
dc.subject.keywordAuthor | Human primary hepatocytes | - |
dc.subject.keywordPlus | INDUCED LIVER-INJURY | - |
dc.subject.keywordPlus | NECROSIS-FACTOR RECEPTOR-1 | - |
dc.subject.keywordPlus | IN-VITRO MODEL | - |
dc.subject.keywordPlus | INFLAMMATORY RESPONSE | - |
dc.subject.keywordPlus | ACETAMINOPHEN | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | INTERLEUKIN-10 | - |
dc.subject.keywordPlus | ROSIGLITAZONE | - |
dc.subject.keywordPlus | EXPRESSION | - |
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