Abstract | OBJECTIVE: METHODS:
Arthritis was induced by immunization with type II collagen. After induction of arthritis, the expression of IDO was analyzed by quantitative reverse transcription-polymerase chain reaction. The effect of IDO deficiency on collagen-induced arthritis was assessed in vivo by administration of 1-methyltryptophan and clinical and histologic evaluation of IDO-deficient mice. The requirement for IDO activation was bypassed by administration of L- kynurenine. RESULTS: IDO was induced in lymph node dendritic cells after collagen immunization. Systemic inhibition of tryptophan catabolism during active arthritis increased disease severity. Conversely, bypassing the requirement for tryptophan degradation by the administration of L- kynurenine resulted in amelioration of arthritis. Furthermore, IDO-deficient mice showed a higher incidence of arthritis and exacerbated disease severity compared with IDO-competent mice. Such increased disease activity in IDO-deficient mice correlated early with increased production of the proinflammatory cytokines interferon-gamma and interleukin-17 by lymph node T cells and later with increased infiltration of Th1 and Th17 cells in the inflamed joints. CONCLUSION:
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Authors | Gabriel Criado, Egle Simelyte, Julia J Inglis, David Essex, Richard O Williams |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 60
Issue 5
Pg. 1342-51
(May 2009)
ISSN: 0004-3591 [Print] United States |
PMID | 19404944
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Indoleamine-Pyrrole 2,3,-Dioxygenase
- Interleukin-17
- Peptide Fragments
- interferon gamma (1-39)
- Kynurenine
- Interferon-gamma
- Tryptophan
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Topics |
- Animals
- Arthritis, Experimental
(physiopathology)
- Indoleamine-Pyrrole 2,3,-Dioxygenase
(analysis, physiology)
- Interferon-gamma
(biosynthesis)
- Interleukin-17
(biosynthesis)
- Kynurenine
(blood, pharmacology)
- Mice
- Mice, Inbred DBA
- Peptide Fragments
(biosynthesis)
- Th1 Cells
(physiology)
- Tryptophan
(metabolism)
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