title: Suppression of experimental autoimmune glomerulonephritis by tryptophan.
abstract: BACKGROUND
  Indoleamine 2, 3-dioxygenase (IDO), a heme-containing dioxygenase, can catalyze tryptophan degradation and produce a local microenvironment with tryptophan depletion and tryptophan metabolites accumulation, which may suppress T cell-mediated immunity and play an important immunosuppressive role in many diseases. Previous studies suggested that tryptophan depletion is an important immunosuppressive mechanism of IDO, while recent evidence shows that tryptophan metabolites may also be useful for inducing the T cell immune tolerance. However, it remains unclear whether tryptophan catabolites play a protective role in anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN), which is a type 1 T-helper (Th1)-mediated autoimmune disease.
  
  
  METHODS
  We examined the effect of tryptophan catabolites, 3-hydroxykynurenine acid and 3-hydroxyanthranilic acid, on renal injury in experimental autoimmune glomerulonephritis (EAG) of Wistar-Kyoto rats and explored their protective mechanism.
  
  
  RESULTS
  Treatment by either 3-hydroxyanthranilic acid or 3-hydroxykynurenic acid attenuated the kidney disease of EAG rats, with decreased glomerular histological injury and inflammatory cell infiltration, lightened urinary protein, and improved renal function compared to phosphate buffered saline-treated EAG rats. This was associated with significantly increased apoptosis and decreased proliferation of splenic activated T cells in vivo, inducing the deviation of cytokines of antigen-special T cells from Th1 to Th2.
  
  
  CONCLUSIONS
  Tryptophan metabolites play an important immunosuppressive role in the development of anti-GBM GN and might offer a new strategy for treating this disease.
authors: Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University Chongqing, Chongqing, China, hwp0518@aliyun.com.
authors: Weiping
authors: W
authors: Hou
authors: Gang
authors: G
authors: Huang
authors: Xuejiao
authors: X
authors: Cao
authors: Yuanyuan
authors: Y
authors: Zhang
authors: Jinbo
authors: J
authors: Zhang
authors: Yan
authors: Y
authors: Li
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology*; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005919:Glomerular Filtration Rate; D007108:Immune Tolerance / Q000187:drug effects*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011921:Rats, Inbred WKY; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan