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During sepsis, secreted extracellular cold\u2010inducible RNA\u2010binding protein (eCIRP) acts as a damage\u2010associated molecular pattern (DAMP), inducing tissue damage by elevating inflammatory cytokines and chemokines. Here, we report that the circulating microRNA 130b\u20103p inhibits eCIRP\u2010mediated sterile and cecal ligation and puncture (CLP)\u2010induced non\u2010sterile inflammation. We find that levels of miR\u2010130b\u20103p are increased in the serum of septic mice and patients and that it strongly interacts with recombinant murine (rm) CIRP\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    and with eCIRP in the serum of septic mice\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    . Combining a miR\u2010130b\u20103p mimic with rmCIRP significantly decreases TNF\u2010\u03b1 release by macrophages compared to only rmCIRP\u2010treated cells. This combined treatment also dose\u2010dependently decreases the affinity of rmCIRP with its receptor TLR4\/MD2. Finally, injection of a miR\u2010130b\u20103p mimic significantly reduces rmCIRP\u2010 or CLP\u2010induced systemic inflammation and acute lung injury in mice. These data show that extracellular miR\u2010130b\u20103p functions as a novel endogenous inhibitor of eCIRP and point to an innovative therapeutic approach to treat inflammatory diseases.\n                  <\/jats:p>","DOI":"10.15252\/embr.201948075","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T02:33:36Z","timestamp":1574908416000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Extracellular microRNA 130b\u20103p inhibits eCIRP\u2010induced inflammation"],"prefix":"10.1038","volume":"21","author":[{"given":"Steven D","family":"Gurien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monowar","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Al\u2010Abed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Nicastro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene F","family":"Coppa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1557-0394","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"BFEMBR201948075_CR1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1189\/jlb.0306164","volume":"81","author":"ME Bianchi","year":"2007","unstructured":"Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. 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