Eupatolide inhibits lipopolysaccharide-induced COX-2 and iNOS expression in RAW264.7 cells by inducing proteasomal degradation of TRAF6

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dc.contributor.authorJ Lee-
dc.contributor.authorN Tae-
dc.contributor.authorJung Joon Lee-
dc.contributor.authorT Kim-
dc.contributor.authorJ H Lee-
dc.date.accessioned2017-04-19T09:18:47Z-
dc.date.available2017-04-19T09:18:47Z-
dc.date.issued2010-
dc.identifier.issn0014-2999-
dc.identifier.uri10.1016/j.ejphar.2010.03.021ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/9557-
dc.description.abstractInula britannica is a traditional medicinal plant used to treat bronchitis, digestive disorders, and inflammation in Eastern Asia. Here, we identified eupatolide, a sesquiterpene lactone from I. britannica, as an inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Eupatolide inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) as well as iNOS and COX-2 protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Eupatolide dose-dependently decreased the mRNA levels and the promoter activities of COX-2 and iNOS in LPS-stimulated RAW264.7 cells. Moreover, eupatolide significantly suppressed the LPS-induced expression of nuclear factor-κappa B (NF-κB) and activator protein-1 (AP-1) reporter genes. Pretreatment of eupatolide inhibited LPS-induced phosphorylation and degradation of IκBα, and phosphorylation of RelA/p65 on Ser-536 as well as the activation of mitogen-activated protein kinases (MAPKs) and Akt in LPS-stimulated RAW264.7 cells. Eupatolide induced proteasomal degradation of tumor necrosis factor receptor-associated factor-6 (TRAF6), and subsequently inhibited LPS-induced TRAF6 polyubiquitination. These results suggest that eupatolide blocks LPS-induced COX-2 and iNOS expression at the transcriptional level through inhibiting the signaling pathways such as NF-κB and MAPKs via proteasomal degradation of TRAF6. Taken together, eupatolide may be a novel anti-inflammatory agent that induces proteasomal degradation of TRAF6, and a valuable compound for modulating inflammatory conditions.-
dc.publisherElsevier-
dc.titleEupatolide inhibits lipopolysaccharide-induced COX-2 and iNOS expression in RAW264.7 cells by inducing proteasomal degradation of TRAF6-
dc.title.alternativeEupatolide inhibits lipopolysaccharide-induced COX-2 and iNOS expression in RAW264.7 cells by inducing proteasomal degradation of TRAF6-
dc.typeArticle-
dc.citation.titleEuropean Journal of Pharmacology-
dc.citation.number1-
dc.citation.endPage180-
dc.citation.startPage173-
dc.citation.volume636-
dc.contributor.affiliatedAuthorJung Joon Lee-
dc.contributor.alternativeName이종규-
dc.contributor.alternativeName태나라-
dc.contributor.alternativeName이정준-
dc.contributor.alternativeName김태호-
dc.contributor.alternativeName이정형-
dc.identifier.bibliographicCitationEuropean Journal of Pharmacology, vol. 636, no. 1, pp. 173-180-
dc.identifier.doi10.1016/j.ejphar.2010.03.021-
dc.subject.keywordCOX-2-
dc.subject.keywordEupatolide-
dc.subject.keywordINOS-
dc.subject.keywordMAPKs-
dc.subject.keywordNF-κB-
dc.subject.keywordTRAF6 degradation-
dc.subject.localCOX-2-
dc.subject.localCox-2-
dc.subject.localEupatolide-
dc.subject.localInducible nitric oxide synthase (iNOS)-
dc.subject.localInducible nitric oxide synthase-
dc.subject.localinducible nnitric oxide synthase-
dc.subject.localiNOS-
dc.subject.localInducible nitric oxide synthease (iNOS)-
dc.subject.localINOS-
dc.subject.localinducible nitric oxide synthase-
dc.subject.localMAPK-
dc.subject.localMAPKs-
dc.subject.localNuclear factor-kappa B-
dc.subject.localnuclear factor κB-
dc.subject.localNf-κb-
dc.subject.localNF-kB-
dc.subject.localnuclear factor kappa B-
dc.subject.localNF-κB (nuclear factor kappa-B)-
dc.subject.localNF-kappaB-
dc.subject.localNuclear factor-κb-
dc.subject.localNF-κ B-
dc.subject.localNF-κB-
dc.subject.localNF-kappa B-
dc.subject.localNuclear factor κB (NF-κB)-
dc.subject.localNuclear factor κB-
dc.subject.localNFκB-
dc.subject.localNf-κB-
dc.subject.localNuclear factor-κB-
dc.subject.localnuclear factorκB-
dc.subject.localNuclear factor (NF)-κB-
dc.subject.localNuclear factor kappa B-
dc.subject.localnuclear factor-κB-
dc.subject.localNF-ΚB-
dc.subject.localNuclear factor-kappa B (NF-κB)-
dc.subject.localNuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB (NF-κB)-
dc.subject.localNFkappaB-
dc.subject.localNuclear factor kappaB-
dc.subject.localTRAF6 degradation-
dc.description.journalClassY-
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