{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:55:49Z","timestamp":1773291349856,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,2,20]],"date-time":"2004-02-20T00:00:00Z","timestamp":1077235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL58688"],"award-info":[{"award-number":["HL58688"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL67040"],"award-info":[{"award-number":["HL67040"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:p>Biliverdin, a product of heme oxygenase\u20101 (HO\u20101) enzymatic action, is converted into bilirubin, which has been considered a waste product in the past. We now show that administration of biliverdin has a salutary effect in organ transplantation. A brief course of treatment with biliverdin leads to long\u2010term survival of H\u20102 incompatible heart allografts. Furthermore, those recipients harboring long\u2010surviving (&gt;100 days) allografts were tolerant to donor antigens indicated by the acceptance of second donor strain hearts but not third\u2010party grafts. Treatment with biliverdin decreased intragraft leukocyte infiltration and inhibited T cell proliferation. Likely related to tolerance induction, biliverdin interferes with T cell signaling by inhibiting activation of nuclear factor of activated T cells (NFAT) and nuclear factor \u03baB (NF\u2010\u03baB), two transcription factors involved in interleukin\u20102 (IL\u20102) transcription and T cell proliferation, as well as suppressing Th1 interferon\u2010\u03b3 (IFN\u2010\u03b3) production in vitro. These findings support the potential use of biliverdin, a natural product, in transplantation and other T cell mediated immune disorders.<\/jats:p>","DOI":"10.1096\/fj.03-0839fje","type":"journal-article","created":{"date-parts":[[2004,2,23]],"date-time":"2004-02-23T20:53:43Z","timestamp":1077569623000},"page":"765-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts"],"prefix":"10.1096","volume":"18","author":[{"given":"Kenichiro","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Surgery Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"}]},{"given":"James","family":"McDaid","sequence":"additional","affiliation":[{"name":"Department of Surgery Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"}]},{"given":"Robert","family":"\u00d6llinger","sequence":"additional","affiliation":[{"name":"Department of Surgery Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"}]},{"given":"Tung\u2010Yu","family":"Tsui","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Hong Kong Medical Center Queen Mary Hospital 102 Pokfulam Road Hong Kong"}]},{"given":"Pascal O.","family":"Berberat","sequence":"additional","affiliation":[{"name":"Department of Surgery Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"}]},{"given":"Anny","family":"Usheva","sequence":"additional","affiliation":[{"name":"Department of Medicine Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"}]},{"given":"Eva","family":"Csizmadia","sequence":"additional","affiliation":[{"name":"Department of Surgery Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"}]},{"given":"R. Neal","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital Harvard Medical School Boston Massachussetts"}]},{"given":"Miguel P.","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Surgery Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"},{"name":"Instituto Gulbenkian de Ci\u00eancia Apartado 14 2781\u2013901 Oeiras Portugal"}]},{"given":"Fritz H.","family":"Bach","sequence":"additional","affiliation":[{"name":"Department of Surgery Immunobiology Research Center, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachussetts"}]}],"member":"311","published-online":{"date-parts":[[2004,2,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/40.1.18"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(01)01494-1"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00601-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3029864"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252626999"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108239200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.2.H643"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2445"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.5.H1613"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.37.1.517"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0196-87"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/2063"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/11072"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/89068"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10925"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-196"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065x.2001.1840124.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200002270-00026"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-197310000-00010"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199104000-00031"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4185"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/15256"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1988.7.47"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13571"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.2.973"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000084381.86567.08"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02088574"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(96)00039-7"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198506000-00017"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199606000-00023"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5994"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/89731"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198406000-00014"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(85)90397-1"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2274"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.03-0839fje","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.03-0839fje","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.03-0839fje","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:32:40Z","timestamp":1761676360000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.03-0839fje"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,20]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1096\/fj.03-0839fje"],"URL":"https:\/\/doi.org\/10.1096\/fj.03-0839fje","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,20]]},"assertion":[{"value":"2003-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}