The molecular basis for the immunomodulatory activities of unconjugated bilirubin

International Journal of Biochemistry and Cell Biology

Volumn 45, Issue 12, 2013, Pages 2843-2851

  Jangi, Sushrut ^a,b   Otterbein, Leo ^a,b   Robson, Simon ^a,b  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Autoimmune disease; Bilirubin; Immunology; Immunomodulation; Lymphocytes

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; AROMATIC HYDROCARBON RECEPTOR; ASCORBIC ACID; BILIRUBIN; BILIRUBIN GLUCURONIDE; BILIVERDIN; CARBON MONOXIDE; COLCHICINE; CORTISONE; FREE RADICAL; GLUCURONIC ACID; HEME; HEME OXYGENASE; HEME OXYGENASE 1; HYDROCORTISONE; HYPOXIA INDUCIBLE FACTOR; IMMUNOGLOBULIN A; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IMMUNOGLOBULIN M; INTERLEUKIN 1; INTERLEUKIN 2; LOW DENSITY LIPOPROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; NICOTINIC ACID; OXIDOREDUCTASE; SUPEROXIDE; UNINDEXED DRUG; UROBILIN; UROBILINOGEN;

ADAPTIVE IMMUNITY; ALLERGY; ANTIOXIDANT ACTIVITY; ASTHMA; BILIRUBIN METABOLISM; CORONARY ARTERY DISEASE; CYTOTOXICITY; ENTERITIS; HUMAN; HYPERBILIRUBINEMIA; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOPATHOLOGY; METABOLISM; MOLECULAR BIOLOGY; MOLECULE; MULTIPLE SCLEROSIS; NONHUMAN; REMISSION; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS;

AUTOIMMUNE DISEASE; BILIRUBIN; IMMUNOLOGY; IMMUNOMODULATION; LYMPHOCYTES;

ANIMALS; AUTOIMMUNE DISEASES; BILIRUBIN; HUMANS; IMMUNOMODULATION; SIGNAL TRANSDUCTION;

EID: 84886745461     PISSN: 13572725     EISSN: 18785875     Source Type: Journal    
DOI: 10.1016/j.biocel.2013.09.014     Document Type: Review

References (86)

1. C.L. Basiglio Protective role of unconjugated bilirubin on complement-mediated hepatocytolysis Biochimica et Biophysica Acta 1770 7 2007 1003 1010 (Pubitemid 46678614)
2. D.A. Benaron, and F.W. Bowen Variation of initial serum bilirubin rise in newborn infants with type of illness Lancet 338 8759 1991 78 81
3. M. Biburger Pivotal advance: heme oxygenase 1 expression by human CD4+ T cells is not sufficient for their development of immunoregulatory capacity Journal of Leukocyte Biology 87 2 2010 193 202
4. K.W. Bock, and C. Kohle Contributions of the Ah receptor to bilirubin homeostasis and its antioxidative and atheroprotective functions Biological Chemistry 391 6 2010 645 653
5. M. Bonelli Heme oxygenase-1 end-products carbon monoxide and biliverdin ameliorate murine collagen induced arthritis Clinical and Experimental Rheumatology 30 1 2012 73 78
6. M. Cainzos Hyperbilirubinemia: jaundice and anergy Hepato- gastroenterology 39 4 1992 330 332
7. D.M. Capuzzi, J.R. Guyton, J.M. Morgan, A.C. Goldberg, R.A. Kreisberg, and O.A. Brusco Efficacy and safety of an extended-release niacin (niaspan): a long-term study American Journal of Cardiology 82 1998 74 81
8. B.M. Choi, and H.O. Pae Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression Biochemical and Biophysical Research Communications 327 4 2005 1066 1071
9. A.A. Chora Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation The Journal of Clinical Investigation 117 2 2007 438 447 (Pubitemid 46203972)
10. C. De Sanctis Neonatal hyperbilirubinemia and response of lymphocytes to phytohemagglutinin Minerva Pediatrica 20 38 1968 2010 2013
11. H.S. de Vries A functional polymorphism in UGT1A1 related to hyperbilirubinemia is associated with a decreased risk for Crohn's disease Journal of Crohn's & Colitis 6 5 2011 597 602
12. E. Diaz del Casrillo Neonatal hyperbilirubinemia. Its relation to the immunological response capacity of the newborn infant Gaceta Medica de Mexico 105 2 1973 185 207
13. G. Endler Is low serum bilirubin an independent risk factor for coronary artery disease in men but not in women? Clinical Chemistry 49 7 2003 1201 1204 (Pubitemid 36751115)
14. L. Ernster, and R. Zetterstrom Bilirubin an uncoupler of oxidative phosphorylation in isolated mitochondria Nature 178 4546 1956 1335 1337
15. A. Fernandes Inflammatory signalling pathways involved in astroglial activation by unconjugated bilirubin Journal of Neurochemistry 96 6 2006 1667 1679 (Pubitemid 43351625)
16. A. Fernandes, and A. Barateiro Astrocyte reactivity to unconjugated bilirubin requires TNF-α and IL-1β receptor signaling pathways Glia 59 1 2011 14 25
17. D. Fischman Bilirubin as a protective factor for rheumatoid arthritis: an NHANES study of 2003-2006 data Journal of Clinical Medicine Research 2 6 2010 256 260
18. V.L. Fromke, and D. Miller Constitutional hepatic dysfunction (CHD Gilbert's disease): a review with special reference to a characteristic increase and prolongation of the hyperbilirubinemic response to nicotinic acid Medicine 51 1972 451 464
19. C. Ghem Serum bilirubin concentration in patients with an established coronary artery disease International Heart Journal 51 2 2010 86 91
20. R. Gold, and L.N. Kappos Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis New England Journal of Medicine 367 September (1) 2012 1098 1107
21. A.C. Gordo Unconjugated bilirubin activates and damages microglia Journal of Neuroscience Research 84 1 2006 194 201 (Pubitemid 44023074)
22. N. Gorin Temporary relief of asthma by jaundice; report of three cases Journal of the American Medical Association 141 1 1949 24
23. D.H. Gregory 2nd, and R.D. Strickland Solubilization and characterization of hepatic bilirubin UDP-glucuronyltransferase Biochimica et Biophysica Acta 327 1 1973 36 45
24. N. Grosser Rosuvastatin upregulates the antioxidant defense protein heme oxygenase-1 Biochemical and Biophysical Research Communications 325 3 2004 871 876 (Pubitemid 39487953)
25. N. Grosser The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells Free Radical Biology & Medicine 37 12 2004 2064 2071 (Pubitemid 39491325)
26. Y. Haga Changes in production of interleukin-1 and interleukin-2 associated with obstructive jaundice and biliary drainage in patients with gastrointestinal cancer Surgery 106 5 1989 842 848 (Pubitemid 19283377)
27. Y. Haga Intracellular accumulation of unconjugated bilirubin inhibits phytohemagglutin-induced proliferation and interleukin-2 production of human lymphocytes Digestive Diseases and Sciences 41 7 1996 1468 1474 (Pubitemid 26245930)
28. Y. Haga, M.A. Tempero, and R.K. Zetterman Unconjugated bilirubin inhibits in vitro cytotoxic T lymphocyte activity of human lymphocytes Biochimica et Biophysica Acta 1317 1 1996 65 70 (Pubitemid 26336596)
29. T.W. Hansen, S.B. Mathiesen, and S.I. Walaas Bilirubin has widespread inhibitory effects on protein phosphorylation Pediatric Research 39 6 1996 1072 1077 (Pubitemid 26170989)
30. P.S. Hench Effect of jaundice on rheumatoid arthritis British Medical Journal 2 4050 1938 394 398
31. P.S. Hench Potential reversibility of rheumatoid arthritis Annals of the Rheumatic Diseases 8 2 1949 90 96
32. P.S. Hench, and E.C. Kendall The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone; compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis Proceedings of the Staff Meetings. Mayo Clinic 24 8 1949 181 197
33. P.N. Hopkins Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease Arteriosclerosis, Thrombosis, and Vascular Biology 16 2 1996 250 255 (Pubitemid 26056243)
34. S.C. Hunt Evidence for a major gene elevating serum bilirubin concentration in Utah pedigrees Arteriosclerosis, Thrombosis, and Vascular Biology 16 8 1996 912 917 (Pubitemid 26266887)
35. J. Kapitulnik Bilirubin: an endogenous product of heme degradation with both cytotoxic and cytoprotective properties Molecular Pharmacology 66 4 2004 773 779 (Pubitemid 39319447)
36. P. Keshavan, and S.J. Schwemberger Unconjugated bilirubin induces apoptosis in colon cancer cells by triggering mitochondrial depolarization International Journal of Cancer 112 3 2004 433 445 (Pubitemid 39390608)
37. F. Kimura Anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy Journal of Gastroenterology and Hepatology 16 4 2001 467 472 (Pubitemid 32397661)
38. A. Kitamura Increased level of heme oxygenase-1 in rheumatoid arthritis synovial fluid Modern Rheumatology/the Japan Rheumatism Association 21 2 2011 150 157
39. F. Kronenberg A genome scan for loci influencing anti-atherogenic serum bilirubin levels European Journal of Human Genetics: EJHG 10 9 2002 539 546 (Pubitemid 35012308)
40. G. Kronke Expression of heme oxygenase-1 in human vascular cells is regulated by peroxisome proliferator-activated receptors Arteriosclerosis, Thrombosis, and Vascular Biology 27 6 2007 1276 1282 (Pubitemid 46809415)
41. B.J. Lauer, and N.D. Spector Hyperbilirubinemia in the newborn Pediatrics in Review/American Academy of Pediatrics 32 8 2011 341 349
42. S.S. Lee Heme oxygenase-1: carbon monoxide, and bilirubin induce tolerance in recipients toward islet allografts by modulating T regulatory cells FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 21 13 2007 3450 3457 (Pubitemid 350075135)
43. S. Leipe, W. Mohrig, and P. Meisel Bilirubin-induced cytomorphological changes in guinea-pig leucocytes Biomedica Biochimica Acta 42 5 1983 503 510 (Pubitemid 14238015)
44. Y. Liu Heme oxygenase-1 plays an important protective role in experimental autoimmune encephalomyelitis Neuroreport 12 9 2001 1841 1845 (Pubitemid 32553694)
45. Y. Liu Bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis Journal of Immunology 181 3 2008 1887 1897
46. Z. Ma, Q. Hong, and Y. Wang Ferulic acid induces heme oxygenase-1 via activation of ERK and Nrf2 Drug Discoveries & Therapeutics 5 6 2011 299 305
47. M.D. Maines The heme oxygenase system: a regulator of second messenger gases Annual Review of Pharmacology and Toxicology 37 1997 517 554 (Pubitemid 27238886)
48. G.L. Mazzone Bilirubin effect on endothelial adhesion molecules expression is mediated by the Nf-κB signaling pathway Bioscience Trends 3 4 2009 151 157
49. I. Miler, J. Vondracek, and L. Hromadkova Bilirubin inhibits the chemotactic activity of human polymorphonuclear leukocytes in vitro Folia Microbiologica 26 5 1981 413 416 (Pubitemid 12170017)
50. R. Motterlini, R. Foresti, R. Bassi, and C.J. Green Curcumin an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress Free Radical Biology and Medicine 28 8 2000 1303 1312 (Pubitemid 30417475)
51. H. Nakamura Inhibitory action of bilirubin on superoxide production by polymorphonuclear leukocytes Biology of the Neonate 52 5 1987 273 278
52. M.S. Nash, J.E. Lewis, T.A. Dyson-Hudson, Y. Szlachcic, F. Yee, and A.J. Mendez Safety, tolerance, and efficacy of extended-release niacin monotherapy for treating dyslipidemia risks in persons with chronic tetraplegia: a randomized multicenter controlled trial Archives of Physical Medicine and Rehabilitation 92 2011 399 410
53. Z. Nejedla The development of immunological factors in infants with hyperbilirubinemia Pediatrics 45 1 1970 102 104
54. W.M. Newberry Depression of lymphocyte reactivity to phytohemagglutinin by serum from patients with liver disease Cellular Immunology 6 1 1973 87 97
55. T. Ohrui Transient relief of asthma symptoms during jaundice: a possible beneficial role of bilirubin Tohoku Journal of Experimental Medicine 199 3 2003 193 196 (Pubitemid 36519472)
56. G.V. Papatheodoridis Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis Gut 43 5 1998 639 644 (Pubitemid 28520097)
57. F. Peng Serum bilirubin concentrations and multiple sclerosis Journal of Clinical Neuroscience 18 10 2011 1355 1359
58. F. Peng Low antioxidant status of serum uric acid: bilirubin and albumin in patients with neuromyelitis optica European Journal of Neurology: The Official Journal of the European Federation of Neurological Societies 19 2 2012 277 283
59. F. Rocuts Bilirubin promotes de novo generation of T regulatory cells Cell Transplantation 19 4 2010 443 451
60. M. Rola-Plezczynski Inhibitory effects of bilirubin on cellular immune responses in man Journal of Pediatrics 86 5 1975 690 696
61. L. Ross, and H. Fremland Myocardial hyperbilirubinemia in a premature infant American Journal of Diseases of Children 115 3 1968 358 361
62. P.T. Roughneen Impaired specific cell-mediated immunity in experimental biliary obstruction and its reversibility by internal biliary drainage The Journal of Surgical Research 41 2 1986 113 125 (Pubitemid 16032188)
63. F.F. Rubaltelli Inhibitory effects of bilirubin and photobilirubin on neonatal and adult T lymphocytes and granulocytes Biology of the Neonate 42 3-4 1982 152 158 (Pubitemid 12018990)
64. H.A. Schwertner, W.G. Jackson, and G. Tolan Association of low serum concentration of bilirubin with increased risk of coronary artery disease Clinical Chemistry 40 1 1994 18 23 (Pubitemid 24050206)
65. S.L. Silva, and A.R. Vaz Features of bilirubin-induced reactive microglia: from phagocytosis to inflammation Neurobiology of Disease 40 December (3) 2010 663 675
66. P. Sima The suppressive effect of continuous infusion of bilirubin on the immune response in mice Folia Microbiologica 25 6 1980 483 490 (Pubitemid 11166010)
67. L. Sirota Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells European Journal of Pediatrics 158 11 1999 910 913 (Pubitemid 29482513)
68. R. Stocker Bilirubin is an antioxidant of possible physiological importance Science 235 4792 1987 1043 1046 (Pubitemid 17049750)
69. J. Svejcar, I. Miler, and J. Pekarek Effect of bilirubin on an in vitro correlate of cell-mediated immunity - the migration inhibition test Journal of Clinical & Laboratory Immunology 13 3 1984 145 149 (Pubitemid 14155954)
70. A. Takahashi The role of heme oxygenase-1 in systemic-onset juvenile idiopathic arthritis Modern Rheumatology/the Japan Rheumatism Association 19 3 2009 302 308
71. R. Tenhunen, H.S. Marver, and R. Schmid The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase Proceedings of the National Academy of Sciences of the United States of America 61 2 1968 748 755
72. Y.H. Thong, A. Ferrante, and D. Ness Neutrophil phagocytic and bactericidal dysfunction induced by bilirubin Australian Paediatric Journal 13 4 1977 287 289 (Pubitemid 8281452)
73. D.W. Vane Impaired immune function in obstructive jaundice Journal of Surgical Research 45 3 1988 287 293
74. V. Vetvicka, L. Fornusek, and J. Zidkova The expression of Fc and complement receptors in young: adult and aged mice Immunology 56 1 1985 73 80 (Pubitemid 16252414)
75. V. Vetvicka The effect of bilirubin on the Fc receptor expression and phagocytic activity of mouse peritoneal macrophages Folia Microbiologica 30 4 1985 373 380 (Pubitemid 15000007)
76. V. Vetvicka The immunosuppressive effects of bilirubin Folia Microbiologica 36 2 1991 112 119
77. L. Vitek Association of systemic lupus erythematosus with low serum bilirubin levels Scandinavian Journal of Rheumatology 39 6 2010 480 484
78. R.L. Walsky, and J.N. Bauman Optimized assays for human UDP-glucuronosyltransferase (UGT) activities: altered alamethicin concentration and utility to screen for UGT inhibitors Drug Metabolism and Disposition 40 5 2012 1051 1065
79. C. Wang, Z. Wang, and S. Tao Preconditioning donor liver with Nodosin perfusion lessens rat ischemia reperfusion injury via heme oxygenase-1 upregulation Journal of Gastroenterology and Hepatology 27 2012 832 840
80. B. Wegiel Biliverdin inhibits Toll-like receptor-4 (TLR4) expression through nitric oxide-dependent nuclear translocation of biliverdin reductase Proceedings of the National Academy of Sciences of the United States of America 108 46 2011 18849 18854
81. T.W. Wu, K.P. Fung, and C.C. Yang Unconjugated bilirubin inhibits the oxidation of human low density lipoprotein better than Trolox Life Sciences 54 25 1994 477 481
82. J. Wu Bilirubin derived from heme degradation suppresses MHC class II expression in endothelial cells Biochemical and Biophysical Research Communications 338 2 2005 890 896 (Pubitemid 41597726)
83. B.J. Wu Niacin inhibits vascular inflammation via the induction of heme oxygenase-1 Circulation 125 1 2012 150 158
84. B.J. Wu, K. Chen, P.J. Barter, and K.-A. Rye Niacin inhibits vascular inflammation via the induction of heme oxygenase Circulation 125 2012 150 158
85. Z. Yang Bilirubin levels in patients with systemic lupus erythematosus: increased or decreased? Rheumatology International 32 8 2011 2423 2430
86. S.D. Zucker, W. Goessling, and A.G. Hoppin Unconjugated bilirubin exhibits spontaneous diffusion through model lipid bilayers and native hepatocyte membranes Journal of Biological Chemistry 274 16 1999 10852 10862 (Pubitemid 29191067)