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dc.contributor.authorXu, J.
dc.contributor.authorFeng, Y.
dc.contributor.authorJeyaram, A.
dc.date.accessioned2019-05-17T13:21:11Z
dc.date.available2019-05-17T13:21:11Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85056710002&doi=10.4049%2fjimmunol.1801008&partnerID=40&md5=57ef1e3cba0f191f29fbece7f6176ab3
dc.identifier.urihttp://hdl.handle.net/10713/9128
dc.description.abstractWe have previously reported that a group of host cellular microRNAs (miRNAs; miR-34a-5p, miR-122-5p, miR-145-5p, miR-146a-5p, miR-210-3p) are released into the blood during sepsis, some of which are capable of inducing complement activation, cytokine production, and leukocyte migration. Extracellular vesicles (EVs) have been proposed as vehicles for extracellular miRNA-mediated intercellular communication. However, the biological function of plasma EVs and the associated miRNAs in sepsis are largely unknown. In this study, we tested the hypothesis that plasma EVs in sepsis are proinflammatory and EV-associated miRNAs are responsible for EV-induced cytokine production. Compared with those of sham mice, the plasma EVs from septic mice were slightly smaller (157 ± 2 versus 191 ± 6 nm, p < 0.0001), but more abundant [(1.6 ± 0.14) × 1010 versus (0.93 ± 0.14) × 1010/ml plasma, p < 0.003]. miRNA array revealed that among 65 miRNAs, 8 miRNAs exhibited >1.5-fold increase in septic EVs compared with sham EVs, including miR-126-3p, miR-122-5p, miR-146a-5p, miR-145-5p, miR-26a-5p, miR-150-5p, miR-222-3p, and miR-181a-5p. Septic but not sham EVs were proinflammatory, promoting IL-6, TNF-α, IL-1β, and MIP-2 production. The effects of EVs were resistant to polymyxin B (an endotoxin inhibitor) but significantly inhibited by anti-miR inhibitors against miR-34a, miR-122, and miR-146a. Moreover, the septic EV-induced cytokine production was attenuated in TLR7−/− or MyD88−/− cells but remained the same in TLR3−/− or Trif−/− cells. In vivo, mice i.p. injected with septic EVs had marked peritoneal neutrophil migration, which was significantly attenuated in MyD88−/− mice. Taken together, these data demonstrate that plasma EVs of septic animals play an important role in inflammation, and EV-associated miRNAs likely mediate the cytokine production via TLR7-MyD88 signaling. Copyright 2018 by The American Association of Immunologists, Inc.en_US
dc.description.urihttps://dx.doi.org/10.4049/jimmunol.1801008en_US
dc.language.isoen_USen_US
dc.publisherAmerican Association of Immunologistsen_US
dc.relation.ispartofJournal of Immunology
dc.subject.meshExtracellular Vesiclesen_US
dc.subject.meshInflammationen_US
dc.subject.meshSepsisen_US
dc.titleCirculating plasma extracellular vesicles from septic mice induce inflammation via microRNA- And TLR7-dependent mechanismsen_US
dc.typeArticleen_US
dc.identifier.doi10.4049/jimmunol.1801008
dc.identifier.pmid30355788


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