{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:09:45Z","timestamp":1790892585841,"version":"4.1.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Cholestatic liver injury leads to cell death and subsequent inflammation and fibrosis. As shown for primary biliary cholangitis (PBC), the mechanisms and circuits between different cell death pathways leading to disease progression are incompletely defined. Common bile duct ligation (BDL) is a well\u2010established murine model to mimic cholestatic liver injury. Here, we hypothesized that pyroptotic cell death by the Nucleotide\u2010Binding Domain, Leucine\u2010Rich\u2010Containing Family, Pyrin Domain\u2010Containing\u20103 (Nlrp3) inflammasome plays an essential role during human and murine cholestasis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>NLRP3 activation was analyzed in humans with cholestatic liver injury. Wild\u2010type (WT) and <jats:italic toggle=\"yes\">Nlrp3\u2212\/\u2212\n                                 <\/jats:italic> mice were subjected to BDL for 2 or 28\u00a0days. Chronic cholestasis in humans and mice is associated with NLRP3 activation and correlates with disease activity. Acute BDL in Nlrp3\u2010deficient mice triggered increased inflammation as well as liver injury, associated with stronger apoptotic and necroptotic cell death. In contrast, NLRP3 deletion led to decreased liver injury and inflammation in chronic cholestasis. Moreover, bridging fibrosis was observed in WT, but not in NLRP3 knockout, mice 28\u00a0days after BDL. In contrast, lack of NLRP3 expression attenuated kidney injury and fibrosis after acute and chronic BDL. Importantly, administration of MCC950, an NLRP3 small molecule inhibitor, reduced BDL\u2010induced disease progression in WT mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>NLRP3 activation correlates with disease activity in patients with PBC. NLRP3 has a differential role during acute and chronic cholestatic liver injury in contrast to kidney injury. Disease progression during chronic cholestasis can be targeted through small molecules and thus suggests a potential clinical benefit for humans, attenuating liver and kidney injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31494","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T04:14:34Z","timestamp":1596514474000},"page":"1836-1854","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":88,"title":["Bidirectional Role of NLRP3 During Acute and Chronic Cholestatic Liver Injury"],"prefix":"10.1097","volume":"73","author":[{"given":"Mick","family":"Frissen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III,University Hospital RWTH Aachen,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3698-5636","authenticated-orcid":false,"given":"Lijun","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III,University Hospital RWTH Aachen,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Markus","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III,University Hospital RWTH Aachen,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Djudjaj","sequence":"additional","affiliation":[{"name":"Institute of Pathology,RWTH Aachen University,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Haybaeck","sequence":"additional","affiliation":[{"name":"Diagnostic & Research Center for Molecular BioMedicine,Institute of Pathology,Medical University of Graz,Graz,Austria"},{"name":"Department of Pathology,Medical Faculty,Otto\u2010von\u2010Guericke University Magdeburg,Magdeburg,Germany"},{"name":"Department of Pathology, Neuropathology, and Molecular Pathology,Medical University of Innsbruck,Innsbruck,Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wree","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III,University Hospital RWTH Aachen,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Rolle\u2010Kampczyk","sequence":"additional","affiliation":[{"name":"Department of Molecular Systems Biology,Helmholtz Centre for Environmental Research,Leipzig,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"von Bergen","sequence":"additional","affiliation":[{"name":"Department of Molecular Systems Biology,Helmholtz Centre for Environmental 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