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001-es BibID:BIBFORM007092
Első szerző:Szántó Sándor (belgyógyász, reumatológus)
Cím:Inhibition of indoleamine 2,3-dioxygenase-mediated tryptophan catabolism accelerates collagen-induced arthritis in mice / Szanto, S., Koreny, T., Mikecz, K., Glant, T. T., Szekanecz, Z., Varga, J.
ISSN:1478-6362 (Electronic)
Megjegyzések:Indoleamine 2,3-dioxygenase (IDO) is one of the initial and rate-limiting enzymes involved in the catabolism of the essential amino acid tryptophan. In cultured cells, the induction of IDO leads to depletion of tryptophan and tryptophan starvation. Recent studies suggest that modulation of tryptophan concentration via IDO plays a fundamental role in innate immune responses. Induction of IDO by interferon-gamma in macrophages and dendritic cells results in tryptophan depletion and suppresses the immune-mediated activation of fibroblasts and T, B, and natural killer cells. To assess the role of IDO in collagen-induced arthritis (CIA), a model of rheumatoid arthritis characterized by a primarily Th1-like immune response, activity of IDO was inhibited by 1-methyl-tryptophan (1-MT) in vivo. The results showed significantly increased incidence and severity of CIA in mice treated with 1-MT. Activity of IDO, as determined by measuring the levels of kynurenine/tryptophan ratio in the sera, was increased in the acute phase of arthritis and was higher in collagen-immunized mice that did not develop arthritis. Treatment with 1-MT resulted in an enhanced cellular and humoral immune response and a more dominant polarization to Th1 in mice with arthritis compared with vehicle-treated arthritic mice. The results demonstrated that development of CIA was associated with increased IDO activity and enhanced tryptophan catabolism in mice. Blocking IDO with 1-MT aggravated the severity of arthritis and enhanced the immune responses. These findings suggest that IDO may play an important and novel role in the negative feedback of CIA and possibly in the pathogenesis of rheumatoid arthritis.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Arthritis, Experimental
Chromatography, High Pressure Liquid
Feedback, Biochemical
Indoleamine-Pyrrole 2,3,-Dioxygenase
Mice, Inbred DBA
Tryptophan/analogs and derivatives
Megjelenés:Arthritis Research and Therapy. - 9 : 3 (2007), p. R50. -
További szerzők:Koreny Tamás Mikecz Katalin Glant Tibor T. Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Varga John
Internet cím:elektronikus változat
elektronikus változat
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