El enzima indoleamina 2,3 dioxigenasa ((IDO) y la tolerancia inmune

  1. María Jesús Coma-del-Corral 1
  2. Pilar Muñiz Rodríguez 2
  3. Joaquín Terán Santos 3
  1. 1 Unidad de Investigación del Hospital Universitario de Burgos
  2. 2 Departamento de Biología y Bioquímica molecular de la Universidad de Burgos
  3. 3 Unidad de Sueño del Hospital Universitario de Burgos.
Revista:
Revista Electrónica de Biomedicina

ISSN: 1697-090X

Año de publicación: 2013

Número: 3

Páginas: 47-58

Tipo: Artículo

Otras publicaciones en: Revista Electrónica de Biomedicina

Resumen

La indolamina 2,3-dioxigenasa (IDO) es un enzima predominante extrahepática intracelular y se encuentra en numerosas células, principalmente macrófagos. La degradación del triptófano genera quinurenina, y esta vía del metabolismo del triptófano, constituye un mecanismo eficaz de modulación de la respuesta inmune. La IDO facilita la tolerancia inmunológica, y es uno de los principales actores implicados en la inhibición de la proliferación celular, incluyendo las células T activadas. La IDO induce la producción de especies reactivas de oxígeno (ROS) y radicales de óxido nítrico (NO). Varias vías implicadas en la regulación de respuesta inmunológica se regulan por mecanismos redox. Las especies reactivas del oxígeno y nitrógeno (ROS-RNS) y otras moléculas activas redox cumplen funciones clave en la inmunidad

Referencias bibliográficas

  • Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med. 2006;8:1-27
  • Salter M, Pogson CI. The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes. Biochem J. 1985;229:499-504.
  • Chen Y, Guillemin GJ. Kynurenine pathway metabolites in humans: disease and healthy States. Int J Tryptophan Res. 2009;2:1-19.
  • Takikawa O. Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated L-tryptophan metabolism. Biochem Biophys Res Commun. 2005;338:12-19.
  • Ball HJ, Sanchez-Perez A, Weiser S, et al. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene. 2007;396:203-213.
  • Metz R, Duhadaway JB, Kamasani U, Laury-kleintop L, Muller AJ, Prendergast GC. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D1-methyl-tryptophan. Cancer Res. 2007;67:7082-7087.
  • Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Wachter H. Characteristics of interferon induced tryptophan metabolism in human cells in vitro. Biochim Biophys Acta.1989;1012:140-147.
  • Werner ER, Bitterlich G, Fuchs D, Hausen A, Reibnegger G, Szabo G, et al. Human macrophages degrade tryptophan upon induction by interferon-gamma. Life Sci. 1987; 41:273-280.
  • Carlin JM, Borden EC, Sondel PM, Byrne GI. Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. J Leukoc Biol.1989; 45:29-34.
  • Brown RR, Ozaki Y, Datta SP, Borden EC, Sondel PM, Malone DG. Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. Adv Exp Med Biol.1991;94:425-35
  • Cozzi A, Zignego AL, Carpendo R, Biagiotti T, Aldinucci A, Monti M, Giannini C, Rosselli M, Laffi G, Moroni F. Low serum tryptophan levels, reduced macrophage IDO activity and high frequency of psychopathology in HCV patients. J Viral Hepat. 2006;13(6):402-408.
  • van der Sluijs KF, Nijhuis M, Levels JH, Florquin S, Mellor AL, Jansen HM, van der Poll T, Lutter R. Influenzainduced expression of indoleamine 2,3-dioxygenase enhances interleukin-10 production and bacterial outgrowth during secondary pneumococcal pneumonia. J Infect Dis. 2006;193(2):214-222.
  • Koenig P, Nagl C, Neurauter G, Schennach H, Brandacher G, Fuchs D. Enhanced degradation of tryptophan in patients on hemodialysis. Clin Nephrol. 2010;74(6):465-470.
  • Müller N, Schwarz MJ. COX-2 inhibition in schizophrenia and major depression. Curr Pharm Des. 2008;14(14):1452-1465.
  • Capuron L, Schroecksnadel S, Féart C, Aubert A, Higueret D, Barberger-Gateau P, Layé S, Fuchs D. Chronic lowgrade inflammation in elderly persons is associated with altered tryptophan and tyrosine metabolism: role in neuropsychiatric symptoms. Biol Psychiatry. 2011;70(2):175-182.
  • López AS, Alegre E, Díaz-Lagares A, García-Girón C, Coma MJ, González A. Effect of 3-hydroxyanthranilic acid in the immunosuppressive molecules indoleamine dioxygenase and HLA-G in macrophages. Immunol Lett. 2008;117(1):91- 95.
  • Cavia-Saiz M, Muñiz P, De Santiago R, Herreros-Villanueva M, Garcia-Giron C, Lopez AS, Coma-Del Corral MJ. Changes in the levels of thioredoxin and indoleamine-2,3-dioxygenase activity in plasma of patients with colorectal cancer treated with chemotherapy. Biochem Cell Biol. 2012;90(2):173-178
  • Palamares T, De Lecea M, Armesto D, Cavia M, Al Kassam D, Alonso-Varona A. Relevance of indoleamine 2, 3-dioxygenase as prognostic biomarker in melanoma patients. In Eur J Cancer. 2013; 49: S863-S863.
  • Song H, Park H, Kim YS, Kim KD, Lee HK, Cho DH, Yang JW, Hur DY. L-kynurenine-induced apoptosis in human NK cells is mediated by reactive oxygen species. Int Immunopharmacol. 2011;11(8):932-938.
  • Curti A, Trabanelli S, Salvestrini V, Baccarani M, Lemoli RM. The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology. Blood 2009; 113:2394-2401.
  • Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281(5380):1191-1193.
  • Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol. 2013;34(3):137-143.
  • Pfefferkorn ER. Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc Natl Acad Sci U S A. 1984; 81:908-912.
  • Taylor MW, Feng GS. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991; 5: 2516-2522.
  • Mándi Y, Vécsei L. The kynurenine system and immunoregulation. J Neural Transm. 2012;119(2):197-209.
  • Gostner JM1, Becker K, Fuchs D, Sucher R. Redox regulation of the immune response. Redox Rep. 2013;18(3):88- 94.
  • Thomas SR, Terentis AC, Cai H, Takikawa O, Levina A, Lay PA, Freewan M, Stocker R. Post-translational regulation of human indoleamine 2,3-dioxygenase activity by nitric oxide. J Biol Chem. 2007;282:23778-23787.
  • Alberati-Giani D, Malherbe P, Ricciardi-Castagnoli P, Köhler C, Denis-Donini S, Cesura AM. Differential regulation of indoleamine 2,3-dioxygenase expression by nitric oxide and inflammatory mediators in IFN-gammaactivated murine macrophages and microglial cells. J Immunol. 1997;159:419-442.
  • Coma-del-Corral MJ, Muniz P, Terán-Santos J. Indoleamine-2,3-dioxygenase activity in plasma of patients with sleep apnea. Unpublished observations, 2013.