{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:09:38Z","timestamp":1791086978109,"version":"4.1.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2013,9,15]]},"abstract":"<jats:p>Although ursodeoxycholic acid (UDCA) has long been used for patients with chronic cholestatic liver diseases, particularly primary biliary cirrhosis, it may modulate the host immune response. This study investigated the effect of UDCA feeding on experimental hepatitis, endotoxin shock, and bacterial infection in mice. C57BL\/6 mice were fed a diet supplemented with or without 0.3% (wt\/vol) UDCA for 4 wk. UDCA improved hepatocyte injury and survival in concanavalin-A (Con-A)-induced hepatitis by suppressing IFN-\u03b3 production by liver mononuclear cells (MNC), especially NK and NKT cells. UDCA also increased survival after lipopolysaccharide (LPS)-challenge; however, it increased mortality of mice following Escherichia coli infection due to the worsening of infection. UDCA-fed mice showed suppressed serum IL-18 levels and production of IL-18 from liver Kupffer cells, which together with IL-12 potently induce IFN-\u03b3 production. However, unlike normal mice, exogenous IL-18 pretreatment did not increase the serum IFN-\u03b3 levels after E. coli, LPS, or Con-A challenge in the UDCA-fed mice. Interestingly, however, glucocorticoid receptor (GR) expression was significantly upregulated in the liver MNC of the UDCA-fed mice but not in their whole liver tissue homogenates. Silencing GR in the liver MNC abrogated the suppressive effect of UDCA on LPS- or Con-A-induced IFN-\u03b3 production. Furthermore, RU486, a GR antagonist, restored the serum IFN-\u03b3 level in UDCA-fed mice after E. coli, LPS, or Con-A challenge. Taken together, these results suggest that IFN-\u03b3-reducing immunomodulatory property of UDCA is mediated by elevated GR in the liver lymphocytes in an IL-12\/18-independent manner.<\/jats:p>","DOI":"10.1152\/ajpgi.00205.2012","type":"journal-article","created":{"date-parts":[[2013,7,19]],"date-time":"2013-07-19T04:53:31Z","timestamp":1374209611000},"page":"G427-G438","source":"Crossref","is-referenced-by-count":30,"title":["Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid on liver lymphocytes in mice"],"prefix":"10.1152","volume":"305","author":[{"given":"Toshimichi","family":"Takigawa","sequence":"first","affiliation":[{"name":"Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Division of Traumatology, Research Institute, National Defense Medical College, Tokorozawa, Saitama, 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