The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts
Abstract
Biliverdin, a product of heme oxygenase-1 (HO-1) 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-term survival of H-2 incompatible heart allografts. Furthermore, those recipients harboring long-surviving (>100 days) allografts were tolerant to donor antigens indicated by the acceptance of second donor strain hearts but not third-party 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 kappaB (NF-kappaB), two transcription factors involved in interleukin-2 (IL-2) transcription and T cell proliferation, as well as suppressing Th1 interferon-gamma (IFN-gamma) production in vitro. These findings support the potential use of biliverdin, a natural product, in transplantation and other T cell mediated immune disorders.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“whereas biliverdin induces tolerance to cardiac allografts by interfering with activation of nuclear factor of activated T cells (NFAT) and nuclear factor-κB (NF-κB), two transcription factors involved in interleukin-2 (IL-2) transcription and T cell activation and expansion (Yamashita et al., 2004).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Yamashita et al., 2004
Citations
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104
Bilirubin Is an Antioxidant of Possible Physiological Importance
Stocker, R., Yamamoto, Y., McDonagh, A. F., Glazer, A. N., & Ames, B. N. (1987) · Science · doi:10.1126/science.3029864 · Cited by 3,502
THE HEME OXYGENASE SYSTEM:A Regulator of Second Messenger Gases
Maines, M. D. (1997) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.37.1.517 · Cited by 2,489
Reduced stress defense in heme oxygenase 1-deficient cells
Poss, K. D., & Tonegawa, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10925 · Cited by 1,294
Biliverdin reductase: A major physiologic cytoprotectant
Barañano, D. E., Rao, M., Ferris, C. D., & Snyder, S. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252626999 · Cited by 1,091
Li, Y.-S., Li, X.-C., Zheng, X., Wells, A., Turka, L., & Strom, T. (1999) · Nature Medicine · doi:10.1038/15256 · Cited by 830
PRIMARILY VASCULARIZED ALLOGRAFTS OF HEARTS IN MICE
Corry, R. J., Winn, H. J., & Russell, P. S. (1973) · Transplantation · doi:10.1097/00007890-197310000-00010 · Cited by 788
Heme oxygenase: A novel target for the modulation of inflammatory response
Willis, D., Moore, A., Frederick, R., & Willoughby, D. A. (1996) · Nature Medicine · doi:10.1038/nm0196-87 · Cited by 782
Doré, S., Takahashi, M., Ferris, C. D., Hester, L. D., Guastella, D. B., & Snyder, S. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2445 · Cited by 699
Cardioprotective Actions by a Water-Soluble Carbon Monoxide–Releasing Molecule
Clark, J., NAUGHTON, P. J., Shurey, S., Green, C. J., Johnson, T. R., Mann, B. E., Foresti, R., & Motterlini, R. (2003) · Circulation Research · doi:10.1161/01.res.0000084381.86567.08 · Cited by 676
Expression of heme oxygenase-1 can determine cardiac xenograft survival
Soares, M. P., Lin, Y., Anrather, J., Csizmadia, E., Takigami, K., Sato, K., Grey, S. T., Colvin, R. B., Choi, A. M. K., Poss, K. D., et al. (1998) · Nature Medicine · doi:10.1038/2063 · Cited by 613
Self-citationA High-Efficiency HeLa Cell Nuclear Transcription Extract
Shapiro, D. J., Sharp, P. A., Wahli, W., & KELLER, M. J. (1988) · DNA · doi:10.1089/dna.1988.7.47 · Cited by 577
Heme oxygenase-1 protects against vascular constriction and proliferation
Duckers, H. J., Boehm, M., True, A. L., Yet, S., San, H., Park, J. L., Webb, R. C., Lee, M.-E., Nabel, G. J., & Nabel, E. G. (2001) · Nature Medicine · doi:10.1038/89068 · Cited by 524
Quantifying the Frequency of Alloreactive T Cells In Vivo: New Answers to an Old Question
Suchin, E. J., Langmuir, P. B., Palmer, E., Sayegh, M. H., Wells, A. D., & Turka, L. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.2.973 · Cited by 517
Haem oxygenase-1 prevents cell death by regulating cellular iron
Ferris, C. D., Jaffrey, S. R., Sawa, A., Takahashi, M., Brady, S. D., Barrow, R. K., Tysoe, S. A., Wolosker, H., Barañano, D. E., Doré, S., et al. (1999) · Nature Cell Biology · doi:10.1038/11072 · Cited by 513
Association of low serum concentration of bilirubin with increased risk of coronary artery disease
Schwertner, H. A., Jackson, W. G., & Tolan, G. D. (1994) · Clinical Chemistry · doi:10.1093/clinchem/40.1.18 · Cited by 472
Sato, K., Balla, J., Otterbein, L. E., Smith, R. N., Brouard, S., Lin, Y., Csizmadia, E., Sévigny, J., Robson, S. C., Vercellotti, G. M., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.6.4185 · Cited by 462
Self-citationGilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels
Vı́tek, L., Jirsa, M., Brodanová, M., Kaláb, M., Marecek, Z., Danzig, V., Novotný, L., & Kotal, P. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(01)00601-3 · Cited by 430
Bach, F. H., Ferran, C. J., Hechenleitner, P., Mark, W., Koyamada, N., Miyatake, T., Winkler, H. J. S., Badrichant, A., Candinas, D., & Ww, H. (1997) · Nature Medicine · doi:10.1038/nm0297-196 · Cited by 419
Self-citationHeme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction
Clark, J., Foresti, R., Sarathchandra, P., Kaur, H., Green, C. J., & Motterlini, R. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.278.2.h643 · Cited by 392
Importance of ICOS–B7RP-1 costimulation in acute and chronic allograft rejection
Özkaynak, E., Gao, W., Shemmeri, N., Wang, C., Gutierrez-Ramos, J.-C., Amaral, J., Qin, S., Rottman, J. B., Coyle, A. J., & Hancock, W. W. (2001) · Nature Immunology · doi:10.1038/89731 · Cited by 314
Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study
Djoussé, L., Levy, D. A., Cupples, L. A., Evans, J. C., D’Agostino, R. B., & Ellison, R. C. (2001) · The American Journal of Cardiology · doi:10.1016/s0002-9149(01)01494-1 · Cited by 262
Tracking the Immunoregulatory Mechanisms Active During Allograft Tolerance
Fueyo, A. S., Weber, M., Domenig, C. M., Strom, T. B., & Zheng, X. X. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.5.2274 · Cited by 173
Heme oxygenase modulates selectin expression in different regional vascular beds
Vachharajani, T. J., Work, J., Issekutz, A. C., & Granger, D. N. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.278.5.h1613 · Cited by 154
SIMPLIFIED MOUSE CERVICAL HEART TRANSPLANTATION USING A CUFF TECHNIQUE
Yasuura, K. (1991) · Transplantation · doi:10.1097/00007890-199104000-00031 · Cited by 119
Usheva, A., & Shenk, T. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13571 · Cited by 106
Self-citationAhmad, Z., Salim, M., & Maines, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108239200 · Cited by 106
Bilirubin Has Widespread Inhibitory Effects on Protein Phosphorylation
Hansen, T. W. R., Mathiesen, S. B. W., & Walaas, S. I. (1996) · Pediatric Research · doi:10.1203/00006450-199606000-00023 · Cited by 102
Mode of Inhibitory Action of Bilirubin on Protein Kinase C
Sano, K., Nakamura, H., & Matsuo, T. (1985) · Pediatric Research · doi:10.1203/00006450-198506000-00017 · Cited by 94
Heme oxygenase‐1, a protective gene that prevents the rejection of transplanted organs
Soares, M. P., Brouard, S., Smith, R. N., & Bach, F. H. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1840124.x · Cited by 84
Self-citationHall, B. M., Jelbart, M., & Dorsch, S. E. (1984) · Transplantation · doi:10.1097/00007890-198406000-00014 · Cited by 83
Inhibition of NF-κB-Dependent T Cell Activation Abrogates Acute Allograft Rejection
Finn, P. W., Stone, J. R., Boothby, M. R., & Perkins, D. L. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5994 · Cited by 64
Haga, Y., Tempero, M. A., Kay, D., & Zetterman, R. K. (1996) · Digestive Diseases and Sciences · doi:10.1007/bf02088574 · Cited by 64
Unconjugated bilirubin inhibits in vitro cytotoxic T lymphocyte activity of human lymphocytes
Haga, Y., Tempero, M. A., & Zetterman, R. K. (1996) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(96)00039-7 · Cited by 44
Woo, J., Iyer, S., Mori, N., & Buelow, R. (2000) · Transplantation · doi:10.1097/00007890-200002270-00026 · Cited by 43
Behavior of helper T lymphocytes in cyclosporine-mediated long-term graft acceptance in the rat
Kupiec‐Weglinski, J. W., Heidecke, C.-D., Araujo, J. L., Abbud‐Filho, M., Towpik, E., ARANEDA, D., Strom, T. B., & Tilney, N. L. (1985) · Cellular Immunology · doi:10.1016/0008-8749(85)90397-1 · Cited by 7
Flagged first, then by citations
Cited by
Sorted by citations
Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications
Ryter, S. W., Alam, J., & Choi, A. M. K. (2006) · Physiological Reviews · doi:10.1152/physrev.00011.2005 · Cited by 2,342
Mechanisms of Cell Protection by Heme Oxygenase-1
Gozzelino, R., Jeney, V., & Soares, M. P. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105600 · Cited by 1,241
Self-citationHeme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria
Pamplona, A., Ferreira, A., Balla, J., Jeney, V., Balla, G., Epiphanio, S., Chora, Â., Rodrigues, C. D., Gregoire, I. P., Cunha-Rodrigues, M., et al. (2007) · Nature Medicine · doi:10.1038/nm1586 · Cited by 560
Self-citationHeme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes
Chiabrando, D., Vinchi, F., Fiorito, V., Mercurio, S., & Tolosano, E. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00061 · Cited by 467
Heme oxygenase–1, oxidation, inflammation, and atherosclerosis
Araujo, J. A., Zhang, M., & Yin, F. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00119 · Cited by 443
Metadata
- Authors
- Yamashita, K., McDaid, J., Öllinger, R., Tsui, T., Berberat, P. O., Usheva, A., Csizmadia, E., Smith, R. N., Soares, M. P., & Bach, F. H.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Queen Mary Hospital (CN)
- Harvard University (US)
- Corresponding author
- Yamashita, Kenichiro
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2004-02-20
- Volume
- 18
- Issue
- 6
- Pages
- 765-767
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2002874458
- Cited by
- 180
- References
- 36
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 15
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Institutes of Health (HL58688, HL67040)
- Pfizer
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- biliverdin, heme oxygenase-1, heart transplantation, allograft tolerance, T cell proliferation, NFAT, NF-κB, interleukin-2 transcription, interferon-gamma, Th1 response, heme degradation
- MeSH terms
- Animals, Biliverdine, Cell Movement, DNA-Binding Proteins, Graft Survival, Heme, Interleukin-2, Isoantigens, Lymphocyte Activation, Nuclear Proteins, T-Lymphocytes, Transcription Factors, Heart Transplantation, NF-kappa B, Transplantation Tolerance, NFATC Transcription Factors, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
