A novel synthetic derivative of melatonin, 5-hydroxy-2 '-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation SCIE SCOPUS

DC Field Value Language
dc.contributor.author Shim, Do-Wan -
dc.contributor.author Shin, Hee Jae -
dc.contributor.author Han, Ji-Won -
dc.contributor.author Ji, Young-Eun -
dc.contributor.author Jang, Cheol-Hun -
dc.contributor.author Koppula, Sushruta -
dc.contributor.author Kang, Tae-Bong -
dc.contributor.author Lee, Kwang-Ho -
dc.date.accessioned 2020-04-20T03:40:34Z -
dc.date.available 2020-04-20T03:40:34Z -
dc.date.created 2020-01-28 -
dc.date.issued 2015-04 -
dc.identifier.issn 0041-008X -
dc.identifier.uri https://sciwatch.kiost.ac.kr/handle/2020.kiost/2503 -
dc.description.abstract Melatonin is substantially reported to possess anti-inflammatory properties. In the present study, we synthesized a novel melatonin derivative, 5-hydroxy-2'-isobutyl-streptochlorin (HIS), which displayed superior anti-inflammatory properties to its parent compound. Further, we explored its underlying mechanisms in cellular and experimental animal models. Lipopolysaccharide was used to induce in vitro inflammatory responses in RAW 264.7 macrophages. LPS-primed macrophages were pulsed with biologically unrelated toxic molecules to evaluate the role of HIS on inflammasome activation. In vivo verifications were carried out using acute lung injury (All) and Escherichia coli-induced septic shock mouse models. HIS inhibited the production of proinflammatory mediators and cytokines such as nitric oxide, cyclooxygenase 2, IL-1 beta, IL-6 and TNF-alpha in LPS-stimulated RAW 264.7 macrophages. HIS suppressed the infiltration of immune cells into the lung and the production of proinflammatory cytokines such as IL-6 and TNF-alpha in broncho-alveolar lavage fluid in the ALI mouse model. Mechanistic studies revealed that the inhibitory effects of HIS were mediated through the regulation of the TIR domain-containing, adaptor-inducing, interferon-beta (TRIF)-dependent signaling pathway from toll-like receptors. Further, HIS attenuated IL-1 beta secretion via the inhibition of NLRP3 inflammasome activation independent of mitochondrial ROS production. Furthermore, HIS suppressed IL-1 beta, IL-6 and interferon-beta production in peritoneal lavage in the Escherichia coli-induced sepsis mouse model. In conclusion, HIS exerted potent anti-inflammatory effects via the regulation of TRIF-dependent signaling and inflammasome activation. Notably, the superior anti-inflammatory properties of this derivative compared with its parent compound could be a promising lead for treating various inflammatory-mediated diseases. (C) 2015 Elsevier Inc. All rights reserved. -
dc.description.uri 1 -
dc.language English -
dc.publisher ACADEMIC PRESS INC ELSEVIER SCIENCE -
dc.title A novel synthetic derivative of melatonin, 5-hydroxy-2 '-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation -
dc.type Article -
dc.citation.endPage 235 -
dc.citation.startPage 227 -
dc.citation.title TOXICOLOGY AND APPLIED PHARMACOLOGY -
dc.citation.volume 284 -
dc.citation.number 2 -
dc.contributor.alternativeName 신희재 -
dc.identifier.bibliographicCitation TOXICOLOGY AND APPLIED PHARMACOLOGY, v.284, no.2, pp.227 - 235 -
dc.identifier.doi 10.1016/j.taap.2015.02.006 -
dc.identifier.scopusid 2-s2.0-84932119293 -
dc.identifier.wosid 000353864000013 -
dc.type.docType Article -
dc.description.journalClass 1 -
dc.description.isOpenAccess N -
dc.subject.keywordPlus NF-KAPPA-B -
dc.subject.keywordPlus NITRIC-OXIDE-SYNTHASE -
dc.subject.keywordPlus ULCERATIVE-COLITIS -
dc.subject.keywordPlus NALP3 INFLAMMASOME -
dc.subject.keywordPlus ESCHERICHIA-COLI -
dc.subject.keywordPlus INTERFERON-BETA -
dc.subject.keywordPlus LIPOPOLYSACCHARIDE -
dc.subject.keywordPlus MACROPHAGES -
dc.subject.keywordPlus EXPRESSION -
dc.subject.keywordPlus PATHWAY -
dc.subject.keywordAuthor Streptochlorin -
dc.subject.keywordAuthor Melatonin -
dc.subject.keywordAuthor Anti-inflammation -
dc.subject.keywordAuthor Inflammasome -
dc.subject.keywordAuthor Sepsis -
dc.subject.keywordAuthor ALI -
dc.relation.journalWebOfScienceCategory Pharmacology & Pharmacy -
dc.relation.journalWebOfScienceCategory Toxicology -
dc.description.journalRegisteredClass scie -
dc.description.journalRegisteredClass scopus -
dc.relation.journalResearchArea Pharmacology & Pharmacy -
dc.relation.journalResearchArea Toxicology -
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Marine Resources & Environment Research Division > Marine Biotechnology &Bioresource Research Department > 1. Journal Articles
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