{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:26:48Z","timestamp":1770100008559,"version":"3.49.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"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":[[2000,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nonobese diabetic (NOD\/LtJ or NOD) mice are resistant to doses of LPS and d-galactosamine that uniformly produce lethality in C57BL\/6J (B6) mice (p &amp;lt; 0.01). Liver caspase-3-like activity, serum transaminase levels (both p &amp;lt; 0.05), and the numbers of apoptotic liver nuclei were also reduced in NOD compared with B6 mice treated with LPS (100 ng) and d-galactosamine (8 mg). NOD mice were also at least 100-fold more resistant to recombinant human TNF-\u03b1 and d-galactosamine treatment than B6 mice (p &amp;lt; 0.001). Binding of recombinant human TNF-\u03b1 to splenocytes from NOD mice was similar to that seen in B6 mice, suggesting that the defect in responsiveness was not due to an inability of recombinant human TNF-\u03b1 to bind the NOD TNF type 1 (p55) receptor. Because the TNF type 1 (p55) receptor shares a common signaling pathway with Fas (CD95), NOD and B6 mice were treated with the Fas agonist antibody, Jo-2. Surprisingly, NOD mice were as sensitive as B6 mice to Fas-induced lethality and hepatic injury. In addition, primary hepatocytes isolated from NOD mice and cultured in vitro in the presence of d-galactosamine with or without TNF-\u03b1 were found to be resistant to apoptosis and cytotoxicity when compared with B6 mice. In contrast, Jo-2 treatment produced similar increases in caspase-3 activity and cytotoxicity in primary hepatocytes from NOD and B6 mice. The resistance to LPS- and TNF-\u03b1-mediated lethality and hepatic injury in d-galactosamine-sensitized NOD mice is apparently due to a post-TNFR binding defect, and independent of signaling pathways shared with Fas.<\/jats:p>","DOI":"10.4049\/jimmunol.165.11.6559","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T22:44:50Z","timestamp":1398120290000},"page":"6559-6567","source":"Crossref","is-referenced-by-count":25,"title":["Reduced Susceptibility of Nonobese Diabetic Mice to TNF-\u03b1 and\n                    <scp>d<\/scp>\n                    -Galactosamine-Mediated Hepatocellular Apoptosis and Lethality"],"prefix":"10.1093","volume":"165","author":[{"given":"Frances R","family":"Bahjat","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine , Gainesville, FL 32610"},{"name":"Department of Pathology, University of Florida College of Medicine , Gainesville, FL 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikas R","family":"Dharnidharka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine , Gainesville, FL 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunitaro","family":"Fukuzuka","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine , Gainesville, FL 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Florida College of Medicine , Gainesville, FL 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Florida College of Medicine , Gainesville, FL 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Clare-Salzler","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine , Gainesville, FL 32610"},{"name":"Department of Pathology, University of Florida College of Medicine , Gainesville, FL 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyle L","family":"Moldawer","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine , Gainesville, FL 32610"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,12,1]]},"reference":[{"key":"2026020213104750400_R1","volume-title":"NOD Mice and Related Strains: Research Applications in Diabetes, AIDS, Cancer and Other Diseases","year":"1998"},{"key":"2026020213104750400_R2","first-page":"5567","volume-title":"J. 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