IFNγ-INDUCED KINURENINE PRODUCTION AND INDOLAMINE 2,3-DIOXYGENASE GENE EXPRESSION IN PSORIASIS
https://doi.org/10.15789/1563-0625-2009-2-3-147-152
Abstract
Abstract. An alternative pathway of L-tryptophan biotransformation is provided by the indolamine 2,3-dioxygenase (INDO), and it results into synthesis of kynurenine and other «distal» metabolites, playing a pivotal role in immunoregulation and down-regulation of immune inflammation. PBMCs from healthy volunteers, patients with progressive vulgar psoriasis (PASI (M±SD) = 25.6±16.6), or patients with psoriatic arthropathy (PASI = 40.3±24.5). The cells were incubated for 24 hrs with IFNγ (500 IU/ml, stimulated cultures) or without cytokine (control cultures). Distinct abnormalities in spontaneous and induced kynurenine production (colorimetric method) and INDO expression (semi-quantitative RT-PCR) were observed in psoriasis and psoriatic arthritis. PBMCs from psoriatic patients, in comparison with healthy donors, were characterized with slightly increased spontaneous kynurenine production, spontaneous and IFNγ-induced INDO expression, while IFNγ-induced kynurenine levels were approximately two times higher. In psoriatic arthritis, spontaneous kynurenine production and INDO expression were significantly lower than in donor’s PBMC, whereas IFNγ-induced kynurenine production were the same as for the donors, while IFNγ – induced INDO expression was markedly increased.
About the Authors
D. A. Kaut
Институт биохимии и генетики Уфимского научного центра РАН, г. Уфа;
Институт иммунологии и физиологии УрО РАН, г. Екатеринбург
Russian Federation
Russian Federation
R. S. Yamidanov
Институт биохимии и генетики Уфимского научного центра РАН, г. Уфа
Russian Federation
Russian Federation
S. V. Sadovnikov
Институт биохимии и генетики Уфимского научного центра РАН, г. Уфа
Russian Federation
Russian Federation
O. M. Kapuler
Институт иммунологии и физиологии УрО РАН, г. Екатеринбург
Russian Federation
Russian Federation
V. A. Vakhitov
Институт биохимии и генетики Уфимского научного центра РАН, г. Уфа
Russian Federation
Russian Federation
S. V. Sibiryak
Институт биохимии и генетики Уфимского научного центра РАН, г. Уфа;
Институт иммунологии и физиологии УрО РАН, г. Екатеринбург
Russian Federation
Russian Federation
References
1. Boasso A., Herbeuval J.-Ph., Hardy A., Winkler C., Shearer G. Regulation of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA-synthetase by CTLA-4-Fc in human CD4+ T cells // Blood. – 2005. – Vol. 105. – P. 1574-1581.
2. Brusko T., Wasserfall C., Agarwal A., Kapturczak M., Atkinson M. An Integral Role for Heme Oxygenase-1 and Carbon Monoxide in Maintaining Peripheral Tolerance by CD4+CD25+ Regulatory T Cells // J. Immunol. – 2005. – Vol. 174. – P. 5181 - 5186.
3. Däiubener W., Wanagat N., Pilz K., Seghrouchni S., Fischer H., Hadding U. A new, simple, bioassay for human IFN-γ // J. Immuno. Meth. – 1994. – Vol. 168. – P. 39-47.
4. Fallarino F., Grohmann U., You S., McGrath B., Cavener D., Vacca C., Orabona C., Bianchi R., Belladonna M., Volpi C., Santamaria P., Fioretti M., Puccetti P.. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells // J. Immunol. – 2006. – Vol. 176. – P. 6752-6761.
5. Frumento G., Rotondo R., Tonetti M., Damonte G., Benatti U., Ferrara G-B. Tryptophanderived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase // J. Exp. Med. – 2002. – Vol. 196. – P. 459-463.
6. Ito M., Ogawa K., Takeuchi K., Nakada A., Heishi M., Suto H., Mitsuishi K., Sugita Y., Ogawa H., Ra C. Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis // J. Dermatol. Sci. – 2004. – Vol. 36. – P. 157-164.
7. Jacob S., Nassiri M., Kerdel F., Vincek V. Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity // Mediators Inflamm. – 2003. – Vol. 12. – P. 309-13.
8. Kaper T., Looger L., Takanaga H., Platten M., Steinman L., Frommer W. Nanosensor detection of an immunoregulatory tryptophan influx/kynurenine efflux cycle // PLoS Biol. – 2007. – Vol. 5 – P. 257.
9. Maes M., Mihaylova I., Ruyter M., Kubera M., Bosmans E. The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression – and other conditions characterized by tryptophan depletion induced by inflammation // Endocrinol Lett. – 2007. – Vol. 28. – P. 826-831.
10. Mellor A., Munn D. Tryptophan catabolism and T cell tolerance: immunosuppression by starvation? // Immunol. Today - 1999. – Vol. 20. – P. 469-473.
11. Mellor A., Munn D. Tryptophan Catabolism and Regulation of Adaptive Immunity // J. Immunol. – 2003. – Vol. 170. – P. 5809-5813.
12. Metzler M., Herrmann H., Rauh M.R., Wassmuth R., Rascher W., Haas J. Intraarticular alteration of tryptophan metabolism in juvenile idiopathic arthritis // Ann Rheum Dis. – 2001. – Vol. 60. - P. 7-17.
13. Tas S., Vervoordeldonk M., Hajji N., Schuitemaker J., Van de Sluijts K., May M., Ghos S., Kapsenberg M., Tak P., De Jong E. Noncanonical NF-kB signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation // Blood. – 2007. – Vol. 110. – P. 1540-1549.
14. Taylor M., Feng G. Relationship between interferon-γ, indoleamine 2,3-dioxygenase, and tryptophan catabolism // FASEB J. - 1991. – Vol. 5. – P. 2516-2522.
15. Torres M., Lopez-Casado M., Lorite P., Rios A. Tryptophan metabolism and indoleamine 2,3-dioxygenase expression in coeliac disease // Clin. Exp. Immunol. – 2007. – Vol. 148. – P. 419-424.
16. Wolf A., Wolf D., Rumpold H., Moschen A., Kaser A., Obrist P., Fuchs D., Brandacher G., Winkler C., Geboes K., Rutgeerts P., Tilg H. Overexpression of Indoleamine 2,3-dioxygenase in human inflammatory bowel disease // Clin. Immunol. – 2004. – Vol. 113. – P. 47-55.
17. Zhu L., Ji F., Wang Y., Zhang Y., Liu Q., Zhang J., Matsushima K., Cao Q., Zhang Y. Synovial Autoreactive T Cells in Rheumatoid Arthritis Resist IDO-Mediated Inhibition // J. Immunol. – 2006. – Vol. 177. – P. 8226-8233.
Review
For citations:
Kaut D.A., Yamidanov R.S., Sadovnikov S.V., Kapuler O.M., Vakhitov V.A., Sibiryak S.V. IFNγ-INDUCED KINURENINE PRODUCTION AND INDOLAMINE 2,3-DIOXYGENASE GENE EXPRESSION IN PSORIASIS. Medical Immunology (Russia). 2009;11(2-3):147-152. (In Russ.) https://doi.org/10.15789/1563-0625-2009-2-3-147-152
Views:
927
Email this article 