{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:41:16Z","timestamp":1792269676623,"version":"4.4.0"},"reference-count":22,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T00:00:00Z","timestamp":1595808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inflammatory diseases of the bile ducts like primary sclerosing colangitis (PSC) are characterized by a robust cellular response targeting the biliary epithelium leading to chronic inflammation and fibrosis. Driving fibro-inflammatory diseases, NOD-like receptors such as NLRP3 have been identified as a central component to immune-mediated pathology. However, to date the role of NLRP3 in biliary diseases has been poorly explored. Here, we addressed the role of NLRP3 in the OVAbil mouse model of antigen-mediated cholangitis. As obesity continues to spread worldwide, we also evaluated the NLRP3 response in experimental cholangitis after high-fat diet exposure. We compared the extent of histopathological liver damage between OVAbil and OVAbilxNLRP3\u2212\/\u2212 mice after either a standard chow or a high-fat diet. Infiltrating immune cells were characterized by flow cytometry and levels of cytokines, chemokines and liver enzymes in blood samples were analyzed at the end of the experiment. We observed a more severe histopathological phenotype of cholangitis in absence of NLRP3, characterized by loss of bile ducts and larger inflammatory foci and higher levels of IL- 6 and CXCL10 as compared with NLRP3 sufficient mice. This phenotype was further exaggerated in the context of obesity, where cholangitis induced in NLRP3-deficient obese mice resulted in further exacerbated histopathology and increased levels of IL-13 and TNF\u03b1, suggesting a diet-specific profile. The absence of NLRP3 caused a supressed IL-17 response. In summary, our data suggest that activation of NLRP3 attenuates this antigen-mediated OVAbil model of cholangitis.<\/jats:p>","DOI":"10.1042\/bsr20200689","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T10:46:17Z","timestamp":1595846777000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["NLRP3 receptor contributes to protection against experimental antigen-mediated cholangitis"],"prefix":"10.1042","volume":"40","author":[{"given":"Marisol\u00a0Ibet","family":"Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Experimental y Regulaci\u00f3n de la Inflamaci\u00f3n Hepato-Intestinal, UBIMED, FES Iztacala, UNAM. Tlalnepantla de Baz, Estado de M\u00e9xico, C.P. 54090, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Vannan","sequence":"additional","affiliation":[{"name":"Boston Scientific 300 Boston Scientific Way Marlborough, MA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertus","family":"Eksteen","sequence":"additional","affiliation":[{"name":"Aspen Woods Clinic, 8561 8A Ave SW Calgary AB T3H 0V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-0261","authenticated-orcid":false,"given":"Jos\u00e9\u00a0Luis","family":"Reyes","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Experimental y Regulaci\u00f3n de la Inflamaci\u00f3n Hepato-Intestinal, UBIMED, FES Iztacala, UNAM. Tlalnepantla de Baz, Estado de M\u00e9xico, C.P. 54090, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"2021111620230617500_B1","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1016\/j.jhep.2017.07.022","article-title":"Primary sclerosing cholangitis - a comprehensive review","volume":"67","author":"Karlsen","year":"2017","journal-title":"J. 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Pharmacol."},{"key":"2021111620230617500_B6","first-page":"3048532","article-title":"Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway","volume":"2018","author":"Wu","year":"2018","journal-title":"Mediators Inflamm."},{"key":"2021111620230617500_B7","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1177\/1753425919826367","article-title":"The NLRP3 inflammasome mediates DSS-induced intestinal inflammation in Nod2 knockout mice","volume":"25","author":"Umiker","year":"2019","journal-title":"Innate Immun"},{"key":"2021111620230617500_B8","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1136\/gut.2009.197822","article-title":"Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome","volume":"59","author":"Bauer","year":"2010","journal-title":"Gut"},{"key":"2021111620230617500_B9","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1002\/ibd.21478","article-title":"NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis","volume":"17","author":"Hirota","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"2021111620230617500_B10","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.immuni.2010.03.003","article-title":"The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis","volume":"32","author":"Zaki","year":"2010","journal-title":"Immunity"},{"key":"2021111620230617500_B11","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1159\/000341681","article-title":"Protective and aggravating effects of Nlrp3 inflammasome activation in IBD models: influence of genetic and environmental factors","volume":"30","author":"Bauer","year":"2012","journal-title":"Dig. Dis."},{"key":"2021111620230617500_B12","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.ajpath.2016.10.010","article-title":"Nlrp3 Activation Induces Il-18 Synthesis and Affects the Epithelial Barrier Function in Reactive Cholangiocytes","volume":"187","author":"Maroni","year":"2017","journal-title":"Am. J. Pathol."},{"key":"2021111620230617500_B13","doi-asserted-by":"publisher","first-page":"536","DOI":"10.3389\/fimmu.2016.00536","article-title":"Deoxycholic Acid Triggers NLRP3 Inflammasome Activation and Aggravates DSS-Induced Colitis in Mice","volume":"7","author":"Zhao","year":"2016","journal-title":"Front. Immunol."},{"key":"2021111620230617500_B14","doi-asserted-by":"publisher","first-page":"83951","DOI":"10.18632\/oncotarget.13796","article-title":"Chenodeoxycholic acid activates NLRP3 inflammasome and contributes to cholestatic liver fibrosis","volume":"7","author":"Gong","year":"2016","journal-title":"Oncotarget"},{"key":"2021111620230617500_B15","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1053\/j.gastro.2006.10.020","article-title":"Novel model of antigen-specific induction of bile duct injury","volume":"131","author":"Buxbaum","year":"2006","journal-title":"Gastroenterology"},{"key":"2021111620230617500_B16","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1038\/s41598-018-21112-7","article-title":"Neutralization of IL-15 abrogates experimental immune-mediated cholangitis in diet-induced obese mice","volume":"8","author":"Reyes","year":"2018","journal-title":"Sci. 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Immunol."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20200689\/889784\/bsr-2020-0689.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20200689\/889784\/bsr-2020-0689.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:53:02Z","timestamp":1637095982000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/40\/8\/BSR20200689\/225894\/NLRP3-receptor-contributes-to-protection-against"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":22,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8,28]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20200689","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,8]]},"published":{"date-parts":[[2020,8]]},"article-number":"BSR20200689"}}