Cited 19 times in
Novel Histone Deacetylase 6 Inhibitor CKD-506 Inhibits NF-κB Signaling in Intestinal Epithelial Cells and Macrophages and Ameliorates Acute and Chronic Murine Colitis
DC Field | Value | Language |
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dc.contributor.author | 천재영 | - |
dc.date.accessioned | 2020-12-01T16:52:02Z | - |
dc.date.available | 2020-12-01T16:52:02Z | - |
dc.date.issued | 2020-05 | - |
dc.identifier.issn | 1078-0998 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/180016 | - |
dc.description.abstract | Background: Selective blocking of HDAC6 has become a promising strategy in treating inflammatory bowel disease. CKD-506 is a novel isoform-selective inhibitor of histone deacetylase 6. The present study was performed to evaluate the effect of CKD-506 on the NF-κB signaling pathway in intestinal epithelial cells (IECs) and macrophages and on murine models of acute and chronic colitis. Methods: RAW264RAW264.7 murine macrophages and COLO 205 human IECs were pretreated with CKD-506 and then stimulated with lipopolysaccharides (LPS). Cytokine expression of TNF-α, interleukin (IL)-6, IL-8, and IL-10 was measured by ELISA. The effect of CKD-506 on NF-κB signaling was evaluated by Western blotting of IκBα phosphorylation/degradation and electrophoretic mobility shift assay. In vivo studies were performed using a dextran sulfate sodium (DSS)-induced acute colitis model, a chronic colitis model in IL-10 knockout mice, and an adoptive transfer model. Colitis was quantified by the disease activity index, colon length, and histopathologic evaluation. Results: CKD-506 suppressed the expression of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α in IECs and macrophages. CKD-506 strongly inhibited IκBα phosphorylation/degradation and the DNA-binding activity of NF-κB. Oral administration of CKD-506 attenuated DSS-induced acute colitis and chronic colitis in IL-10-/- and adoptive transfer models. CKD-506 ameliorated weight loss, disease activity, and histopathologic score in colitis mice and downregulated IκBα phosphorylation and pro-inflammatory cytokine production significantly. Conclusions: CKD-506 blocked NF-κB signaling in IECs and macrophages and ameliorated experimental acute and chronic murine colitis models, which suggests that CKD-506 is a promising candidate for inflammatory bowel disease treatment as a small molecular medicine. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Lippincott Williams & Wilkins | - |
dc.relation.isPartOf | INFLAMMATORY BOWEL DISEASES | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Novel Histone Deacetylase 6 Inhibitor CKD-506 Inhibits NF-κB Signaling in Intestinal Epithelial Cells and Macrophages and Ameliorates Acute and Chronic Murine Colitis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Jung Won Lee | - |
dc.contributor.googleauthor | Soung-Min Lee | - |
dc.contributor.googleauthor | Jaeyoung Chun | - |
dc.contributor.googleauthor | Jong Pil Im | - |
dc.contributor.googleauthor | Su-Kil Seo | - |
dc.contributor.googleauthor | Nina Ha | - |
dc.contributor.googleauthor | Young Il Choi | - |
dc.contributor.googleauthor | Joo Sung Kim | - |
dc.identifier.doi | 10.1093/ibd/izz317 | - |
dc.contributor.localId | A05701 | - |
dc.relation.journalcode | J01060 | - |
dc.identifier.eissn | 1536-4844 | - |
dc.identifier.pmid | 31895948 | - |
dc.identifier.url | https://academic.oup.com/ibdjournal/article/26/6/852/5694342 | - |
dc.subject.keyword | histone deacetylase 6 inhibitor | - |
dc.subject.keyword | NF-κB | - |
dc.subject.keyword | acute colitis | - |
dc.subject.keyword | chronic colitis | - |
dc.subject.keyword | inflammatory bowel diseases | - |
dc.contributor.alternativeName | Cheon, Jae Young | - |
dc.contributor.affiliatedAuthor | 천재영 | - |
dc.citation.volume | 26 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 852 | - |
dc.citation.endPage | 862 | - |
dc.identifier.bibliographicCitation | INFLAMMATORY BOWEL DISEASES, Vol.26(6) : 852-862, 2020-05 | - |
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