{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:54:04Z","timestamp":1791150844734,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4322,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:sec><jats:title\/><jats:p>Breakdown of cellular proteins is a highly regulated process, and the ubiquitin\u2013proteasome pathway is the major proteolytic system in the cell. It regulates the levels of numerous proteins that control gene expression and cell division, as well as responses to stress and inflammation. Recent studies have reported abnormalities in proteasome function in alcoholic liver disease (ALD). Moreover, a direct relation has been reported between impaired proteasome function and oxidative stress in experimental models of ALD. Neutrophil infiltration is a hallmark of ALD, and activated neutrophils are thought to play a role in the pathology of ALD. As a potent neutrophil chemoattractant and activator, interleukin 8 (IL\u20138) likely plays a key mechanistic role in many forms of liver injury. In this study, we evaluated the effects of inhibition of proteasome function on expression and release of IL\u20138 by human fetal hepatocytes and hepatoma cells. Our data demonstrate that inhibition of proteasome function in hepatocytes leads to apoptotic cell death. Decreased hepatocyte survival coincides with enhanced expression of IL\u20138, both at the protein and the messenger RNA (mRNA) levels. This increase in IL\u20138 is independent of nuclear factor \u03baB (NF\u2013\u03baB) activation and is associated with an increase in c\u2013Jun N\u2013terminal kinase (JNK) and activator protein\u20131 (AP\u20131) activity. In conclusion, hepatocytes dying because of inhibition of proteasome function produce massive quantities of the proinflammatory chemokine IL\u20138, possibly resulting in neutrophil infiltration, increased inflammation, and liver injury.<\/jats:p><\/jats:sec>","DOI":"10.1053\/jhep.2003.50470","type":"journal-article","created":{"date-parts":[[2003,10,23]],"date-time":"2003-10-23T14:25:20Z","timestamp":1066919120000},"page":"1178-1187","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":78,"title":["Inhibition of Proteasome Function Leads to Nf\u2013\u03baB\u2013Independent Il\u20138 Expression in Human Hepatocytes"],"prefix":"10.1097","volume":"38","author":[{"given":"Swati","family":"Joshi-Barve","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirish 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