Cited by 180Heme Oxygenase-1 and Carbon MonoxideTransplantation: Methods and OutcomesT-cell and B-cell Immunology

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.

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Crossref · 10.1096/fj.03-0839fje

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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
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

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