{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:45:21Z","timestamp":1791297921207,"version":"4.1.0"},"reference-count":48,"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":2495,"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":[[2008,11]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      <jats:bold>The farnesoid X receptor (FXR) is a nuclear receptor that plays key roles in hepatoprotection by maintaining the homeostasis of liver metabolism. FXR null mice display strong hepatic inflammation and develop spontaneous liver tumors. In this report, we demonstrate that FXR is a negative modulator of nuclear factor \u03baB (NF-\u03baB)\u2013mediated hepatic inflammation. Activation of FXR by its agonist ligands inhibited the expression of inflammatory mediators in response to NF-\u03baB activation in both HepG2 cells and primary hepatocytes cultured<\/jats:bold>\n                      <jats:bold>in vitro<\/jats:bold>\n                      <jats:bold>.<\/jats:bold>\n                      <jats:bold>In vivo<\/jats:bold>\n                      <jats:bold>, compared with wild-type controls, FXR\u2212\/\u2212 mice displayed elevated messenger RNA (mRNA) levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-inducible protein 10, and interferon-\u03b3 in response to lipopolysaccharide (LPS). Examination of FXR\u2212\/\u2212 livers showed massive necroses and inflammation after treatment with LPS at a dose that does not induce significant liver damage or inflammation in wild-type mice. Moreover, transfection of a constitutively active FXR expression construct repressed the iNOS, COX-2, interferon-inducible protein 10 and interferon-\u03b3 mRNA levels induced by LPS administration. FXR activation had no negative effects on NF-\u03baB-activated antiapoptotic genes, suggesting that FXR selectively inhibits the NF-\u03baB-mediated hepatic inflammatory response but maintains or even enhances the cell survival response. On the other hand, NF-\u03baB activation suppressed FXR-mediated gene expression both<\/jats:bold>\n                      <jats:bold>in vitro<\/jats:bold>\n                      <jats:bold>and<\/jats:bold>\n                      <jats:bold>in vivo<\/jats:bold>\n                      <jats:bold>, indicating a negative crosstalk between the FXR and NF-\u03baB signaling pathways. Our findings reveal that FXR is a negative mediator of hepatic inflammation, which may contribute to the critical roles of FXR in hepatoprotection and suppression of hepatocarcinogenesis. (Hepatology 2008;48:1632\u20131643.)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.22519","type":"journal-article","created":{"date-parts":[[2008,7,10]],"date-time":"2008-07-10T10:59:14Z","timestamp":1215687554000},"page":"1632-1643","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":604,"title":["Farnesoid X receptor antagonizes nuclear factor \u03baB in hepatic inflammatory 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