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Within the liver, they have been linked to several inflammatory diseases including nonalcoholic fatty liver disease (NAFLD). In this study, we found that inflammatory macrophages cause injury to hepatocytes, in part by a cell\u2013cell crosstalk phenomenon involving the secretion of EVs containing pro-inflammatory cargo. Incorporation of these inflammatory signals into EV requires the cleavage of the trafficking adaptor protein RILP, which, as previously shown, results from inflammasome-mediated caspase-1 activation. RILP cleavage can be blocked by overexpressing a dominant negative, non-cleavable form of RILP (ncRILP). EV preparations from ncRILP-expressing cells are, by themselves, sufficient to suppress inflammatory effects in hepatocytes. These results suggest that both direct RILP manipulation and\/or supplying ncRILP-modified EVs could be used as a novel therapy for the treatment of inflammatory liver diseases.<\/jats:p>","DOI":"10.1242\/jcs.260691","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T08:31:10Z","timestamp":1681374670000},"source":"Crossref","is-referenced-by-count":13,"title":["Inflammatory macrophage to hepatocyte signals can be prevented by extracellular vesicle reprogramming"],"prefix":"10.1242","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-7420","authenticated-orcid":false,"given":"Priyanka","family":"Ghosh","sequence":"first","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Internal Medicine , , Kansas City, KS 66160 , USA"},{"name":"Liver Center, University of Kansas Medical Center 2 , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyo","family":"Sasaki","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Internal Medicine , , Kansas City, KS 66160 , USA"},{"name":"Liver Center, University of Kansas Medical Center 2 , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel Aranzazu","family":"Pulido Ruiz","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Internal Medicine , , Kansas City, KS 66160 , USA"},{"name":"Liver Center, University of Kansas Medical Center 2 , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla E.","family":"King","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Internal Medicine , , Kansas City, KS 66160 , USA"},{"name":"Liver Center, University of Kansas Medical Center 2 , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8744-8873","authenticated-orcid":false,"given":"Steven A.","family":"Weinman","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Internal Medicine , , Kansas City, KS 66160 , USA"},{"name":"Liver Center, University of Kansas Medical Center 2 , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-6661","authenticated-orcid":false,"given":"Ann L.","family":"Wozniak","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center 1 Department of Internal Medicine , , Kansas City, KS 66160 , USA"},{"name":"Liver Center, University of Kansas Medical Center 2 , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"2023051211441677900_JCS260691C1","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1016\/j.bbrc.2018.08.013","article-title":"Caspase-1 regulates cellular trafficking via cleavage of the Rab7 adaptor protein RILP","volume":"503","author":"Adams","year":"2018","journal-title":"Biochem. 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