Anti-inflammatory effects of dabrafenib in vitro and in vivo
DC Field | Value | Language |
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dc.contributor.author | Lee, In-Chul | - |
dc.contributor.author | Kim, Jongdoo | - |
dc.contributor.author | Bae, Jong-Sup | - |
dc.date.available | 2020-02-27T18:42:42Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-06 | - |
dc.identifier.issn | 0008-4212 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6074 | - |
dc.description.abstract | The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases (drug repositioning). Drug repositioning refers to the development of existing drugs for new indications. Dabrafenib (DAB) is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Here, we tested the possible use of DAB in the treatment of lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The anti-inflammatory activities of DAB were determined by measuring permeability, neutrophils adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and mice. We found that DAB inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion and transendothelial migration of neutrophils to human endothelial cells. DAB also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore, DAB suppressed the production of tumor necrosis factor-alpha (TNF-alpha) or interleukin (IL)-6 and the activation of nuclear factor-kappa B (NF-kappa B) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with DAB resulted in reduced LPS-induced lethal endotoxemia. These results suggest that DAB possesses anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS | - |
dc.relation.isPartOf | CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY | - |
dc.subject | NF-KAPPA-B | - |
dc.subject | HUMAN ENDOTHELIAL-CELLS | - |
dc.subject | ACTIVATED PROTEIN-KINASE | - |
dc.subject | ADHESION MOLECULE EXPRESSION | - |
dc.subject | TNF-ALPHA | - |
dc.subject | BARRIER DYSFUNCTION | - |
dc.subject | INFLAMMATORY RESPONSES | - |
dc.subject | IMMUNE-RESPONSES | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | EXISTING DRUGS | - |
dc.title | Anti-inflammatory effects of dabrafenib in vitro and in vivo | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000402318700011 | - |
dc.identifier.doi | 10.1139/cjpp-2016-0519 | - |
dc.identifier.bibliographicCitation | CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, v.95, no.6, pp.697 - 707 | - |
dc.identifier.scopusid | 2-s2.0-85020081703 | - |
dc.citation.endPage | 707 | - |
dc.citation.startPage | 697 | - |
dc.citation.title | CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY | - |
dc.citation.volume | 95 | - |
dc.citation.number | 6 | - |
dc.contributor.affiliatedAuthor | Kim, Jongdoo | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | drug repositioning | - |
dc.subject.keywordAuthor | dabrafenib | - |
dc.subject.keywordAuthor | lipopolysaccharide | - |
dc.subject.keywordAuthor | inflammation | - |
dc.subject.keywordAuthor | barrier integrity | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | HUMAN ENDOTHELIAL-CELLS | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | ADHESION MOLECULE EXPRESSION | - |
dc.subject.keywordPlus | TNF-ALPHA | - |
dc.subject.keywordPlus | BARRIER DYSFUNCTION | - |
dc.subject.keywordPlus | INFLAMMATORY RESPONSES | - |
dc.subject.keywordPlus | IMMUNE-RESPONSES | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | EXISTING DRUGS | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Physiology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Physiology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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