{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T22:23:25Z","timestamp":1759530205604,"version":"3.30.0"},"reference-count":38,"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":3956,"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":[[2004,11]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Nuclear factor \u03baB (NF-\u03baB) has a central role in coordinating the expression of a wide variety of genes that control immune responses and is also recognized as an antiapoptotic transcription factor. Here, we focused on the role of the NF-\u03baB signaling pathway in the interaction between inflammatory cells and hepatocytes in liver inflammation. We found that pretreatment of mice with adenoviruses expressing a mutant form of the inhibitor \u03baB superrepressor (Ad5I\u03baB), a NF-\u03baB inhibitor, reduced the migration of inflammatory cells and cytokine and chemokine expression in the liver 12 hours after a single intravenous injection of an anti-CD40 antibody (\u03b1CD40) compared with mice infected with control adenoviruses (Ad5LacZ). We also confirmed reductions in cytokine production by macrophages, T cells, and natural killer (NK) cells in the liver of Ad5I\u03baB-treated mice by FACS analysis. However, \u03b1CD40 treatment in Ad5I\u03baB-infected mice induced elevation of serum alanine aminotransferase at 24 hours, and the liver injury was associated with massive hepatocyte apoptosis. Furthermore, interferon gamma (IFN-\u03b3) production by NK cells and T cells was increased and stimulated tumor necrosis factor alpha (TNF-\u03b1) production by macrophages in the Ad5I\u03baB-infected liver. Moreover, the liver injury was completely suppressed by the administration of anti-IFN-\u03b3 and anti-TNF-\u03b1. These results suggest that inhibition of NF-\u03baB activity suppressed \u03b1CD40-induced liver inflammation at an early phase, resulting in a reduction in cytokine and chemokine production, whereas it sensitized hepatocytes to TNF-\u03b1-induced apoptosis and exacerbated liver injury at the late phase. <jats:underline>In conclusion<\/jats:underline>, NF-\u03baB exerts pivotal activities at inflammatory sites, and caution should be exercised in NF-\u03baB-targeted therapy of liver disease. (Hepatology 2004;40:1180-1189.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20432","type":"journal-article","created":{"date-parts":[[2004,10,15]],"date-time":"2004-10-15T07:02:25Z","timestamp":1097823745000},"page":"1180-1189","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":20,"title":["Pivotal role of nuclear factor \u03baB signaling in anti-CD40-induced liver injury in 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