Exosomal delivery of NF-kappa B inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models

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dc.contributor.authorSheller-Miller, Samanthako
dc.contributor.authorRadnaa, Enkhtuyako
dc.contributor.authorYoo, Jae-Kwangko
dc.contributor.authorKim, Eunsooko
dc.contributor.authorChoi, Kyungsunko
dc.contributor.authorKim, Youngeunko
dc.contributor.authorKim, Yunako
dc.contributor.authorRichardson, Laurenko
dc.contributor.authorChoi, Chulheeko
dc.contributor.authorMenon, Ramkumarko
dc.date.accessioned2021-03-02T08:50:05Z-
dc.date.available2021-03-02T08:50:05Z-
dc.date.created2021-02-23-
dc.date.created2021-02-23-
dc.date.issued2021-01-
dc.identifier.citationSCIENCE ADVANCES, v.7, no.4, pp.eabd3865-
dc.identifier.issn2375-2548-
dc.identifier.urihttp://hdl.handle.net/10203/281117-
dc.description.abstractAccumulation of immune cells and activation of the pro-inflammatory transcription factor NF-kappa B in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-kappa B activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-kappa B inhibitor, termed super-repressor (SR) I kappa B alpha. Treatment with SR exosomes (1 x 10(10 )per intraperitoneal injection) after lipopolysaccharide (LPS) challenge on gestation day 15 (E15) prolonged gestation by over 24 hours (PTB <= E18.5) and reduced maternal inflammation (n >= 4). Furthermore, using a transgenic model in which fetal tissues express the red fluorescent protein tdTomato while maternal tissues do not, we report that LPS-induced PTB in mice is associated with influx of fetal innate immune cells, not maternal, into feto-maternal uterine tissues. SR packaged in exosomes provides a stable and specific intervention for reducing the inflammatory response associated with PTB.-
dc.languageEnglish-
dc.publisherAMER ASSOC ADVANCEMENT SCIENCE-
dc.titleExosomal delivery of NF-kappa B inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models-
dc.typeArticle-
dc.identifier.wosid000610099000018-
dc.identifier.scopusid2-s2.0-85099903157-
dc.type.rimsART-
dc.citation.volume7-
dc.citation.issue4-
dc.citation.beginningpageeabd3865-
dc.citation.publicationnameSCIENCE ADVANCES-
dc.identifier.doi10.1126/sciadv.abd3865-
dc.contributor.localauthorChoi, Chulhee-
dc.contributor.nonIdAuthorSheller-Miller, Samantha-
dc.contributor.nonIdAuthorRadnaa, Enkhtuya-
dc.contributor.nonIdAuthorYoo, Jae-Kwang-
dc.contributor.nonIdAuthorKim, Eunsoo-
dc.contributor.nonIdAuthorChoi, Kyungsun-
dc.contributor.nonIdAuthorKim, Youngeun-
dc.contributor.nonIdAuthorKim, Yuna-
dc.contributor.nonIdAuthorRichardson, Lauren-
dc.contributor.nonIdAuthorMenon, Ramkumar-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusTRANSFORMING-GROWTH-FACTOR-
dc.subject.keywordPlusINTERLEUKIN-10 INHIBITION-
dc.subject.keywordPlusTHERAPEUTIC IMPLICATIONS-
dc.subject.keywordPlusLABOR-
dc.subject.keywordPlusINFECTION-
dc.subject.keywordPlusPREGNANCY-
dc.subject.keywordPlusMEMBRANES-
dc.subject.keywordPlusCERVIX-
dc.subject.keywordPlusDRUGS-
dc.subject.keywordPlusPROSTAGLANDINS-
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