Cited 25 times in
Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 구본녀 | - |
dc.date.accessioned | 2016-02-04T11:40:31Z | - |
dc.date.available | 2016-02-04T11:40:31Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/140948 | - |
dc.description.abstract | Suppression 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.statementOfResponsibility | open | - |
dc.format.extent | 711~717 | - |
dc.relation.isPartOf | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Cytokines/antagonists & inhibitors | - |
dc.subject.MESH | Cytokines/biosynthesis | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | HEK293 Cells | - |
dc.subject.MESH | HeLa Cells | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Jurkat Cells | - |
dc.subject.MESH | Lipopolysaccharides/toxicity | - |
dc.subject.MESH | Lymphocyte Activation | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred BALB C | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | NF-kappa B/antagonists & inhibitors* | - |
dc.subject.MESH | NF-kappa B/genetics | - |
dc.subject.MESH | NF-kappa B/immunology | - |
dc.subject.MESH | Protein Structure, Tertiary/genetics | - |
dc.subject.MESH | Recombinant Proteins/genetics | - |
dc.subject.MESH | Recombinant Proteins/immunology | - |
dc.subject.MESH | Recombinant Proteins/pharmacology | - |
dc.subject.MESH | Sepsis/etiology | - |
dc.subject.MESH | Sepsis/metabolism | - |
dc.subject.MESH | Sepsis/therapy* | - |
dc.subject.MESH | T-Lymphocytes/immunology | - |
dc.subject.MESH | T-Lymphocytes/metabolism | - |
dc.subject.MESH | Transcription Factor RelA/antagonists & inhibitors | - |
dc.subject.MESH | Transcription Factor RelA/genetics | - |
dc.subject.MESH | Transcription Factor RelA/immunology | - |
dc.subject.MESH | Transcription, Genetic | - |
dc.subject.MESH | Transduction, Genetic | - |
dc.title | Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Anesthesiology (마취통증의학) | - |
dc.contributor.googleauthor | Sung-Dong Park | - |
dc.contributor.googleauthor | So Yeong Cheon | - |
dc.contributor.googleauthor | Tae-Yoon Park | - |
dc.contributor.googleauthor | Bo-Young Shin | - |
dc.contributor.googleauthor | Hyunju Oh | - |
dc.contributor.googleauthor | Sankar Ghosh | - |
dc.contributor.googleauthor | Bon-Nyeo Koo | - |
dc.contributor.googleauthor | Sang-Kyou Lee | - |
dc.identifier.doi | 10.1016/j.bbrc.2015.07.008 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00193 | - |
dc.relation.journalcode | J00281 | - |
dc.identifier.eissn | 1090-2104 | - |
dc.identifier.pmid | 26159927 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0006291X15302400 | - |
dc.subject.keyword | Inflammation | - |
dc.subject.keyword | Intra-nucleus delivery | - |
dc.subject.keyword | NF-κB | - |
dc.subject.keyword | RelA (p65) | - |
dc.subject.keyword | Sepsis | - |
dc.contributor.alternativeName | Ku, Bon Nyo | - |
dc.contributor.affiliatedAuthor | Ku, Bon Nyo | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 464 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 711 | - |
dc.citation.endPage | 717 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.464(3) : 711-717, 2015 | - |
dc.identifier.rimsid | 30411 | - |
dc.type.rims | ART | - |
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