{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T20:47:57Z","timestamp":1781297277030,"version":"3.54.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"The National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL132941"],"award-info":[{"award-number":["R01HL132941"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"K12 Child Health Research grant from the University of Colorado Department of Pediatrics"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,24]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acetaminophen (APAP) overdose results in high morbidity and mortality, with limited treatment options. Increased understanding of the cellular signaling pathways activated in response to toxic APAP exposure is needed to provide insight into novel therapeutic strategies. Toxic APAP exposure induces hepatic nuclear factor kappa B (NF\u03baB) activation. NF\u03baB signaling has been identified to mediate the proinflammatory response but also induces a prosurvival and regenerative response. It is currently unknown whether potentiating NFkB activation would be injurious or advantageous after APAP overdose. The NF\u03baB inhibitory protein beta (I\u03baB\u03b2) dictates the duration and degree of the NF\u03baB response following exposure to oxidative injuries. Thus, we sought to determine whether I\u03baB\u03b2\/NF\u03baB signaling contributes to APAP-induced hepatic injury. At late time points (24\u2009h) following toxic APAP exposures, mice expressing only I\u03baB\u03b2 knock-in mice (AKBI mice) exhibited increased serologic evidence of hepatic injury. This corresponded with increased histologic injury, specifically related to sinusoidal dilatation. When compared with wild type mice, AKBI mice demonstrated sustained hepatic nuclear translocation of the NF\u03baB subunits p65 and p50, and enhanced NF\u03baB target gene expression. This included increased expression of interleukin-6 (Il-6), a known contributor to hepatic sinusoidal dilation. This transcriptional response corresponded with increased plasma protein content of Il-6, as well as increased activation of signal transducer and activator of transcription 3.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab131","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T11:10:55Z","timestamp":1635419455000},"page":"158-169","source":"Crossref","is-referenced-by-count":9,"title":["APAP-Induced I\u03baB\u03b2\/NF\u03baB Signaling Drives Hepatic Il6 Expression and Associated Sinusoidal Dilation"],"prefix":"10.1093","volume":"185","author":[{"given":"Laura G","family":"Sherlock","sequence":"first","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durganili","family":"Balasubramaniyan","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Grayck","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"De Dios","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Zarate","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Orlicky","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"De Dios","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde J","family":"Wright","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"2022042010330011500_kfab131-B1","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1016\/j.jhep.2014.12.016","article-title":"Acute liver failure: A curable disease by 2024?","volume":"62","author":"Bernal","year":"2015","journal-title":"J. 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