0 263

Cited 12 times in

Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

DC FieldValueLanguage
dc.contributor.author구본녀-
dc.date.accessioned2016-02-04T11:40:31Z-
dc.date.available2016-02-04T11:40:31Z-
dc.date.issued2015-
dc.identifier.issn0006-291X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140948-
dc.description.abstractSuppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration.-
dc.description.statementOfResponsibilityopen-
dc.format.extent711~717-
dc.relation.isPartOfBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCells, Cultured-
dc.subject.MESHCytokines/antagonists & inhibitors-
dc.subject.MESHCytokines/biosynthesis-
dc.subject.MESHFemale-
dc.subject.MESHHEK293 Cells-
dc.subject.MESHHeLa Cells-
dc.subject.MESHHumans-
dc.subject.MESHJurkat Cells-
dc.subject.MESHLipopolysaccharides/toxicity-
dc.subject.MESHLymphocyte Activation-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHNF-kappa B/antagonists & inhibitors*-
dc.subject.MESHNF-kappa B/genetics-
dc.subject.MESHNF-kappa B/immunology-
dc.subject.MESHProtein Structure, Tertiary/genetics-
dc.subject.MESHRecombinant Proteins/genetics-
dc.subject.MESHRecombinant Proteins/immunology-
dc.subject.MESHRecombinant Proteins/pharmacology-
dc.subject.MESHSepsis/etiology-
dc.subject.MESHSepsis/metabolism-
dc.subject.MESHSepsis/therapy*-
dc.subject.MESHT-Lymphocytes/immunology-
dc.subject.MESHT-Lymphocytes/metabolism-
dc.subject.MESHTranscription Factor RelA/antagonists & inhibitors-
dc.subject.MESHTranscription Factor RelA/genetics-
dc.subject.MESHTranscription Factor RelA/immunology-
dc.subject.MESHTranscription, Genetic-
dc.subject.MESHTransduction, Genetic-
dc.titleIntranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Anesthesiology (마취통증의학)-
dc.contributor.googleauthorSung-Dong Park-
dc.contributor.googleauthorSo Yeong Cheon-
dc.contributor.googleauthorTae-Yoon Park-
dc.contributor.googleauthorBo-Young Shin-
dc.contributor.googleauthorHyunju Oh-
dc.contributor.googleauthorSankar Ghosh-
dc.contributor.googleauthorBon-Nyeo Koo-
dc.contributor.googleauthorSang-Kyou Lee-
dc.identifier.doi10.1016/j.bbrc.2015.07.008-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00193-
dc.relation.journalcodeJ00281-
dc.identifier.eissn1090-2104-
dc.identifier.pmid26159927-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0006291X15302400-
dc.subject.keywordInflammation-
dc.subject.keywordIntra-nucleus delivery-
dc.subject.keywordNF-κB-
dc.subject.keywordRelA (p65)-
dc.subject.keywordSepsis-
dc.contributor.alternativeNameKu, Bon Nyo-
dc.contributor.affiliatedAuthorKu, Bon Nyo-
dc.rights.accessRightsnot free-
dc.citation.volume464-
dc.citation.number3-
dc.citation.startPage711-
dc.citation.endPage717-
dc.identifier.bibliographicCitationBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.464(3) : 711-717, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.