Publication Date:
2005-11-08
Description:
Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (T(H)1) cytokines. N-(3,4,-Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating T(H)1-mediated autoimmune diseases such as MS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Platten, Michael -- Ho, Peggy P -- Youssef, Sawsan -- Fontoura, Paulo -- Garren, Hideki -- Hur, Eun Mi -- Gupta, Rohit -- Lee, Lowen Y -- Kidd, Brian A -- Robinson, William H -- Sobel, Raymond A -- Selley, Michael L -- Steinman, Lawrence -- New York, N.Y. -- Science. 2005 Nov 4;310(5749):850-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA. michael.platten@uni-tuebingen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16272121" target="_blank"〉PubMed〈/a〉
Keywords:
Adoptive Transfer
;
Animals
;
Anti-Inflammatory Agents, Non-Steroidal/administration &
;
dosage/pharmacology/*therapeutic use
;
Antigen-Presenting Cells/drug effects/immunology
;
Brain/pathology
;
Cell Line
;
Cytokines/biosynthesis
;
Disease Models, Animal
;
Encephalomyelitis, Autoimmune, Experimental/*drug therapy/immunology
;
Female
;
Histocompatibility Antigens Class II/immunology/metabolism
;
Immune Tolerance
;
Immunosuppressive Agents/pharmacology/therapeutic use
;
Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism
;
Interferon-gamma/immunology
;
Lymphocyte Activation
;
Mice
;
Mice, Transgenic
;
Microglia/drug effects/immunology
;
Multiple Sclerosis/drug therapy/immunology/pathology
;
Myelin Proteins/immunology
;
Signal Transduction
;
Spinal Cord/pathology
;
T-Lymphocytes/immunology
;
Th1 Cells/immunology
;
Th2 Cells/immunology
;
Tryptophan/*metabolism
;
ortho-Aminobenzoates/administration & dosage/pharmacology/*therapeutic use
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
