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
Department of Surgery, Immunobiology Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Ave., Boston, MA 02215, USA.
FASEB J. 2004 Apr;18(6):765-7. doi: 10.1096/fj.03-0839fje. Epub 2004 Feb 20.
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.
胆红素是血红素加氧酶-1（HO-1）酶促作用的产物，可转化为胆红素，胆红素在过去一直被视为一种废物。我们现在表明，给予胆红素在器官移植中具有有益作用。用胆红素进行短期治疗可使H-2不相容的心脏同种异体移植物长期存活。此外，那些携带长期存活（>100天）同种异体移植物的受者对供体抗原具有耐受性，这通过接受第二个供体品系心脏而非第三方移植物来表明。胆红素治疗减少了移植物内白细胞浸润并抑制了T细胞增殖。可能与耐受性诱导有关，胆红素通过抑制活化T细胞核因子（NFAT）和核因子κB（NF-κB）的活化来干扰T细胞信号传导，这两种转录因子参与白细胞介素-2（IL-2）转录和T细胞增殖，并且在体外抑制Th1干扰素-γ（IFN-γ）的产生。这些发现支持了天然产物胆红素在移植和其他T细胞介导的免疫疾病中的潜在用途。
