Histone deacetylase inhibitor KBH-A42 inhibits cytokine production in RAW 264.7 macrophage cells and in vivo endotoxemia model

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dc.contributor.authorYongseok Choi-
dc.contributor.authorSong Kyu Park-
dc.contributor.authorHwan Mook Kim-
dc.contributor.authorJong Soon Kang-
dc.contributor.authorYeo Dae Yoon-
dc.contributor.authorS B Han-
dc.contributor.authorJ W Han-
dc.contributor.authorJ S Yang-
dc.contributor.authorG Han-
dc.date.accessioned2017-04-19T09:12:13Z-
dc.date.available2017-04-19T09:12:13Z-
dc.date.issued2008-
dc.identifier.issnI000-0028-
dc.identifier.uri10.3858/emm.2008.40.5.574ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/8707-
dc.description.abstractIn light of the anti-inflammatory properties of histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), we examined a new HDAC inhibitor KBH-A42 for its anti-inflammatory activities. KBH-A42 showed noteworthy anti-inflammatory properties in vitro via suppression of the production of TNF-α, a proinflammatory cytokine, and nitric oxide (NO), a proinflammatory effector molecule, in LPS-stimulated RAW264.7 cells and peritoneal macrophages. It also inhibited TNF-α production in vivo as demonstrated in a LPS-induced mouse endotoxemia model. The levels of TNF-α, IL-1β, IL-6 and iNOS mRNAs determined by RT-PCR propose that the inhibition of these pro-inflammatory mediators by KBH-A42 resulted from inhibiting expression of these genes. However, the EMSA study to see the effect of KBH-A42 on the binding of NF-κB, a transcription factor, to a specific DNA sequence showed that the binding of NF-κB to DNA was not changed regardless of increasing the concentration of KBH-A42 in the presence and absence of LPS stimulation. Interestingly, DNA binding of another transcription factor AP-1 dose-dependently increased by KBH-A42. KBH-A42 differentially regulated the phosphorylation of MAP kinases. While the phosphprylation of ERK1/2 and SAPK/JNK was not affected by KBH-A42, the phosphorylation of p38 decreased by KBH-A42. These results showed that KBH-A42 inhibits production of proinflammatory cytokines in macrophages by decreasing their mRNA levels, and p38 kinase is involved in the KBH-A42-mediated inhibition.n light of the anti-inflammatory properties of histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), we examined a new HDAC inhibitor KBH-A42 for its anti-inflammatory activities. KBH-A42 showed noteworthy anti-inflammatory properties in vitro via suppression of the production of TNF-α, a proinflammatory cytokine, and nitric oxide (NO), a proinflammatory effector molecule, in LPS-stimulated RAW264.7 cells and peritoneal macrophages. It also inhibited TNF-α production in vivo as demonstrated in a LPS-induced mouse endotoxemia model. The levels of TNF-α, IL-1β, IL-6 and iNOS mRNAs determined by RT-PCR propose that the inhibition of these pro-inflammatory mediators by KBH-A42 resulted from inhibiting expression of these genes. However, the EMSA study to see the effect of KBH-A42 on the binding of NF-κB, a transcription factor, to a specific DNA sequence showed that the binding of NF-κB to DNA was not changed regardless of increasing the concentration of KBH-A42 in the presence and absence of LPS stimulation. Interestingly, DNA binding of another transcription factor AP-1 dose-dependently increased by KBH-A42. KBH-A42 differentially regulated the phosphorylation of MAP kinases. While the phosphprylation of ERK1/2 and SAPK/JNK was not affected by KBH-A42, the phosphorylation of p38 decreased by KBH-A42. These results showed that KBH-A42 inhibits production of proinflammatory cytokines in macrophages by decreasing their mRNA levels, and p38 kinase is involved in the KBH-A42-mediated inhibition.-
dc.publisherSpringer-Nature Pub Group-
dc.titleHistone deacetylase inhibitor KBH-A42 inhibits cytokine production in RAW 264.7 macrophage cells and in vivo endotoxemia model-
dc.title.alternativeHistone deacetylase inhibitor KBH-A42 inhibits cytokine production in RAW 264.7 macrophage cells and in vivo endotoxemia model-
dc.typeArticle-
dc.citation.titleExperimental and Molecular Medicine-
dc.citation.number5-
dc.citation.endPage581-
dc.citation.startPage574-
dc.citation.volume40-
dc.contributor.affiliatedAuthorSong Kyu Park-
dc.contributor.affiliatedAuthorHwan Mook Kim-
dc.contributor.affiliatedAuthorJong Soon Kang-
dc.contributor.affiliatedAuthorYeo Dae Yoon-
dc.contributor.alternativeName최용석-
dc.contributor.alternativeName박성규-
dc.contributor.alternativeName김환묵-
dc.contributor.alternativeName강종순-
dc.contributor.alternativeName윤여대-
dc.contributor.alternativeName한상배-
dc.contributor.alternativeName한증환-
dc.contributor.alternativeName양지선-
dc.contributor.alternativeName한균희-
dc.identifier.bibliographicCitationExperimental and Molecular Medicine, vol. 40, no. 5, pp. 574-581-
dc.identifier.doi10.3858/emm.2008.40.5.574-
dc.subject.keywordAnti-inflammatory agents-
dc.subject.keywordHistone deacetylases-
dc.subject.keywordNF-κ B-
dc.subject.keywordNitric oxide-
dc.subject.keywordTranscription factor AP-1-
dc.subject.keywordTumor necrosis factor-α-
dc.subject.keywordVorinostat-
dc.subject.localAnti-inflammatory agents-
dc.subject.localanti-inflammatory agent-
dc.subject.localHistone deacetylase-
dc.subject.localhistone deacetylase (HDAC)-
dc.subject.localHistone deacetylases-
dc.subject.localhistone deacetylase-
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.localNO-
dc.subject.localnitric oxide-
dc.subject.localnitric oxide (NO)-
dc.subject.localNitric oxide-
dc.subject.localNO (Nitric oxide)-
dc.subject.localnitric oxide.-
dc.subject.localNitric oxid-
dc.subject.localNitric oxide (NO)-
dc.subject.localTranscription factor AP-1-
dc.subject.localTumor necrosis fa tor-α-
dc.subject.localTNFα-
dc.subject.localTumor necrosis factor (TNF)-α-
dc.subject.localTnf-α-
dc.subject.localTNF-a-
dc.subject.localTNF-alpha-
dc.subject.localTumor necrosis factor-α-
dc.subject.localtumor necrosis factor-alpha-
dc.subject.localTNFa-
dc.subject.localTumor necrosis factor alpha-
dc.subject.localTumor necrosis factor-alpha-
dc.subject.localTNF-α-
dc.subject.localtumor necrosis factor-α-
dc.subject.localVorinostat-
dc.description.journalClassY-
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Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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