Document Detail


Indoleamine 2,3 dioxygenase in intestinal disease.
MedLine Citation:
PMID:  23283180     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Several gastrointestinal diseases including the inflammatory bowel diseases (IBDs) and malignancy are associated with elevated expression of indoleamine 2,3 dioxygenase-1 (IDO1). IDO1 initiates tryptophan catabolism along a pathway that generates several bioactive kynurenine-based metabolites. Promotion of T-cell-mediated tolerance and antimicrobial effects are among the variety of functions attributed to IDO1 activity. Recent advances addressing the diverse implications of gut-associated IDO1 expression are herein reviewed.
RECENT FINDINGS: In active IBD, IDO1 is highly expressed both in the cells of the lamina propria and epithelium. Experimental models demonstrate that IDO1 promotes gut immune homeostasis by limiting inflammatory responses and protecting the epithelium. In human colon cancer, high expression of IDO1 by the neoplastic epithelium correlates with poor prognosis. The serum kynurenine : tryptophan ratio is elevated in both active Crohn's disease and in colon cancer, suggesting this measurement may prove useful as a disease biomarker. IDO1 inhibitors have moved to clinical trials providing new hope as immunotherapy for advanced malignancy.
SUMMARY: IDO1 activity significantly shapes gastrointestinal disease pathophysiology and severity. Measures of IDO1 activity may be useful as a disease biomarker. Manipulation of IDO1 activity has great potential as a treatment for both inflammatory and malignancy associated gastrointestinal disease.
Authors:
Matthew A Ciorba
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in gastroenterology     Volume:  29     ISSN:  1531-7056     ISO Abbreviation:  Curr. Opin. Gastroenterol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-05     Completed Date:  2013-07-22     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8506887     Medline TA:  Curr Opin Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  146-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers / blood
Colitis / enzymology
Colonic Neoplasms / diagnosis
Gastrointestinal Diseases / diagnosis
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*,  physiology
Inflammatory Bowel Diseases / enzymology
Intestinal Diseases / enzymology*
Mice
Tumor Markers, Biological / metabolism
Grant Support
ID/Acronym/Agency:
DK089016/DK/NIDDK NIH HHS; K08 DK089016/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 0/Tumor Markers, Biological
Comments/Corrections

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