{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:46:31Z","timestamp":1791071191232,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"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":[[2002,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intrinsic defects in macrophage (M\u03c6) cytokine production characterize many autoimmune-prone mouse strains. Aberrant levels of IL-12, for example, are produced by M\u03c6 isolated from young mice prone to lupus (MRL and NZB\/W) and diabetes (nonobese diabetic (NOD)) well before the appearance of disease signs. Evaluation of the possible mechanism(s) underlying the abnormal regulation of IL-12 in these strains revealed novel patterns of Rel family protein binding to the unique p40 NF-\u03baB site in the IL-12 p40 promoter, whereas binding patterns to Ets and CCAAT enhancer binding protein\/\u03b2 sites were normal. In particular, the heightened production of IL-12 by NOD M\u03c6 is associated with elevated levels of the trans-activating p50\/c-Rel (p65) complex compared with the nonfunctional p50\/p50 dimer. Conversely, the dramatically impaired production of IL-12 by both NZB\/W and MRL\/+ M\u03c6 is associated with a predominance of p50\/p50 and reduced p50\/c-Rel(p65) binding. Mechanistically, the unique pattern seen in the lupus strains reflects elevated p50 and reduced c-Rel nuclear protein levels. In NOD extracts, the level of c-Rel is elevated compared with that in lupus strains, but not when compared with that in normal A\/J. However, the extent of c-Rel tyrosine phosphorylation noted in NOD extracts is more than double that seen in any other strain. Levels of p65 were similar in all strains tested. These findings reveal that a common mechanism, involving dysregulation of c-Rel and p50, may be used to determine the aberrant IL-12 levels that have the potential to predispose specific mouse strains to systemic or organ-specific autoimmunity.<\/jats:p>","DOI":"10.4049\/jimmunol.169.1.581","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:33:01Z","timestamp":1398025981000},"page":"581-586","source":"Crossref","is-referenced-by-count":45,"title":["Aberrant Production of IL-12 by Macrophages from Several Autoimmune-Prone Mouse Strains Is Characterized by Intrinsic and Unique Patterns of NF-\u03baB Expression and Binding to the IL-12 p40 Promoter"],"prefix":"10.1093","volume":"169","author":[{"given":"Jiajian","family":"Liu","sequence":"first","affiliation":[{"name":"Arthritis Section, Department of Medicine, Boston University Medical Center , Boston MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Beller","sequence":"additional","affiliation":[{"name":"Arthritis Section, Department of Medicine, Boston University Medical Center , Boston MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,7,1]]},"reference":[{"key":"2026020208203990300_R1","first-page":"275","volume-title":"Immunity","year":"1998"},{"key":"2026020208203990300_R2","first-page":"495","volume-title":"Annu. Rev. Immunol.","year":"1998"},{"key":"2026020208203990300_R3","first-page":"243","volume-title":"Ann, Rheum. Dis.","year":"2000"},{"key":"2026020208203990300_R4","first-page":"356","volume-title":"Nature","year":"1988"},{"key":"2026020208203990300_R5","first-page":"2534","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020208203990300_R6","first-page":"5610","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020208203990300_R7","first-page":"6878","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020208203990300_R8","first-page":"440","volume-title":"J. Leukocyte Biol.","year":"2001"},{"key":"2026020208203990300_R9","first-page":"1106","volume-title":"Diabetes","year":"2000"},{"key":"2026020208203990300_R10","first-page":"2951","volume-title":"Eur. J. Immunol.","year":"1993"},{"key":"2026020208203990300_R11","first-page":"208","volume-title":"Ann. NY Acad. Sci.","year":"1996"},{"key":"2026020208203990300_R12","first-page":"118","volume-title":"Clin. Exp. Immunol.","year":"2001"},{"key":"2026020208203990300_R13","first-page":"1483","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020208203990300_R14","first-page":"743","volume-title":"Mol. Immunol.","year":"1995"},{"key":"2026020208203990300_R15","first-page":"5258","volume-title":"Mol. Cell. Biol.","year":"1995"},{"key":"2026020208203990300_R16","first-page":"4572","volume-title":"Mol. Cell. Biol.","year":"1997"},{"key":"2026020208203990300_R17","first-page":"10389","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2026020208203990300_R18","first-page":"26790","volume-title":"J. Biol. Chem.","year":"1993"},{"key":"2026020208203990300_R19","first-page":"23","volume-title":"Autoimmunity.","year":"1995"},{"key":"2026020208203990300_R20","first-page":"1273","volume-title":"Diabetes","year":"1990"},{"key":"2026020208203990300_R21","first-page":"1682","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020208203990300_R22","first-page":"1461","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020208203990300_R23","first-page":"12705","volume-title":"Proc. Nat. Acad. Sci. USA","year":"2000"},{"key":"2026020208203990300_R24","first-page":"295","volume-title":"J. Interferon Cytokine Res.","year":"1997"},{"key":"2026020208203990300_R25","first-page":"302","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020208203990300_R26","first-page":"2881","volume-title":"Oncogene","year":"1997"},{"key":"2026020208203990300_R27","first-page":"5678","volume-title":"Mol. Cell. Biol.","year":"1998"},{"key":"2026020208203990300_R28","first-page":"279","volume-title":"Nat. Med.","year":"2001"},{"key":"2026020208203990300_R29","first-page":"2095","volume-title":"Oncogene","year":"1992"},{"key":"2026020208203990300_R30","first-page":"583","volume-title":"Biochem. J.","year":"2000"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/169\/1\/581\/62556894\/581.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/169\/1\/581\/62556894\/581.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:35:02Z","timestamp":1770039302000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/169\/1\/581\/8024737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7,1]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2002,7,1]]},"published-print":{"date-parts":[[2002,7,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.169.1.581","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2002,7]]},"published":{"date-parts":[[2002,7,1]]}}}