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

Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts

Yamashita, Kenichiro, McDaid, James, Öllinger, Robert, Tsui, Tung‐Yu, Berberat, Pascal O., Usheva, Anny, Csizmadia, Eva, Smith, R. Neal +2 more·2004·The FASEB Journal
DOI 10.1096/fj.03-0839fje
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1096/fj.03-0839fje

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • Biliverdin induces tolerance to cardiac allografts by interfering with activation of NFAT and NF-κB, two transcription factors involved in IL-2 transcription and T cell activation and expansion.

    “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

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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
DOI
10.1096/fj.03-0839fje
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
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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