{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T06:57:52Z","timestamp":1760425072754,"version":"3.40.3"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immune hepatic injury induced by Con A results primarily from IFN-\u03b3\u2013mediated inflammation, followed by hepatic cell death. Glycogen synthase kinase (GSK)-3, which acts proapoptotically and is proinflammatory, is also important for facilitating IFN-\u03b3 signaling. We hypothesized a pathogenic role for GSK-3 in Con A hepatic injury. Con A stimulation caused GSK-3 activation in the livers of C57BL\/6 mice. Inhibiting GSK-3 reduced Con A hepatic injury, including hepatic necrosis and apoptosis, inflammation, infiltration of T cells and granulocytes, and deregulated expression of adhesion molecule CD54. Con A induced hepatic injury in an IFN-\u03b3 receptor 1-dependent manner. Con A\/IFN-\u03b3 induced activation and expression of STAT1 in a GSK-3\u2013dependent manner. GSK-3 facilitated IFN-\u03b3\u2013induced inducible NO synthase, but had limited effects on CD95 upregulation and CD95-mediated hepatocyte apoptosis in vitro. Notably, inhibiting GSK-3 decreased Con A-induced IFN-\u03b3 production in both wild-type and IFN-\u03b3 receptor 1-deficient C57BL\/6 mice. In Con A-activated NKT cells, GSK-3 was also activated and was required for nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-\u03b3, but it was not required for CD95 ligand expression or activation-induced cell death. These results demonstrate the dual and indispensable role of GSK-3 in Con A hepatic injury by facilitating IFN-\u03b3\u2013induced hepatopathy.<\/jats:p>","DOI":"10.4049\/jimmunol.1100770","type":"journal-article","created":{"date-parts":[[2011,8,27]],"date-time":"2011-08-27T05:13:51Z","timestamp":1314422031000},"page":"3867-3877","source":"Crossref","is-referenced-by-count":8,"title":["Glycogen Synthase Kinase-3 Facilitates Con A-Induced IFN-\u03b3\u2013Mediated Immune Hepatic Injury"],"prefix":"10.1093","volume":"187","author":[{"given":"Cheng-Chieh","family":"Tsai","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Institute of Clinical Medicine, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Department of Nursing, Chung Hwa University of Medical Technology , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Institute of Clinical Medicine, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Yuan","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yee-Shin","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Department of Microbiology and Immunology, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Department of Microbiology and Immunology, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kao-Chi","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiou-Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Institute of Clinical Medicine, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Department of Microbiology and Immunology, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University Medical College , Tainan 701 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,10,1]]},"reference":[{"key":"2025032410372446200_r1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jhep.2008.08.009","article-title":"The importance of immune dysfunction in determining outcome in acute liver failure","volume":"49","author":"Antoniades","year":"2008","journal-title":"J. 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