Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts.
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Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts. / Yamashita, Kenichiro; McDaid, James; Ollinger, Robert; Tsui, Tung Yu; Berberat, Pascal O; Usheva, Anny; Csizmadia, Eva; Smith, R Neal; Soares, Miguel P; Bach, Fritz H.
In: FASEB J, Vol. 18, No. 6, 6, 2004, p. 765-767.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts.
AU - Yamashita, Kenichiro
AU - McDaid, James
AU - Ollinger, Robert
AU - Tsui, Tung Yu
AU - Berberat, Pascal O
AU - Usheva, Anny
AU - Csizmadia, Eva
AU - Smith, R Neal
AU - Soares, Miguel P
AU - Bach, Fritz H
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 18
SP - 765
EP - 767
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 6
M1 - 6
ER -