title: Enhanced expression of indoleamine 2,3-dioxygenase in Helicobacter pylori-infected human gastric mucosa modulates Th1/Th2 pathway and interleukin 17 production.
abstract: BACKGROUND
  Indoleamine 2,3 dioxygenase (IDO) interferes with immune responses. Host immune response against Helicobacter pylori is involved in the persistence of the infection and its related diseases.
  
  
  OBJECTIVE
  To investigate the role of IDO in the regulation of Th1/Th2 and Th17 pathways in H. pylori infection.
  
  
  METHODS
  Gastric biopsy samples were taken from 42 patients who underwent endoscopy and evaluated for the expression of IDO by Western blotting. Gastritis was assessed by the Sydney system score. In a subgroup of patients, biopsies were treated with the IDO inhibitor 1-methyl-L-tryptophan and the expression of interferon-γ (IFN-γ) mRNA and that of T-bet, interleukin-17 (IL-17), and IL-4 determined by real-time PCR and Western blotting, respectively.
  
  
  RESULTS
  IDO expression was found to be enhanced (p = .001) in gastric biopsies from H. pylori-infected (n = 18) compared with uninfected (n = 24) patients. Levels of IDO expression were inversely related to the gastritis score (r = -.684, p = .002) in H. pylori-infected gastric mucosa, but not in uninfected mucosa. In gastric biopsy cultures, IDO inhibition increased the expression of IFN-γ mRNA (p = .014), T-bet (p = .045), and IL-17 (p = .02) while decreasing that of IL-4 (p = .048).
  
  
  CONCLUSIONS
  In H. pylori-infected human gastric mucosa, an enhanced expression of IDO is capable of modulating Th1/Th2 and Th17 pathways. This mechanism lowers gastric inflammation, possibly contributing to the persistence of H. pylori. Targeting the IDO pathway may be a new strategy for modulating H. pylori-induced mucosal immune response.
authors.affiliation: Department of Health Science, University of Catanzaro "Magna Graecia", Catanzaro, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Larussa
authors.forename: Isabella
authors.initials: I
authors.lastname: Leone
authors.forename: Evelina
authors.initials: E
authors.lastname: Suraci
authors.forename: Immacolata
authors.initials: I
authors.lastname: Nazionale
authors.forename: Teresa
authors.initials: T
authors.lastname: Procopio
authors.forename: Francesco
authors.initials: F
authors.lastname: Conforti
authors.forename: Ludovico
authors.initials: L
authors.lastname: Abenavoli
authors.forename: Marta L
authors.initials: ML
authors.lastname: Hribal
authors.forename: Maria
authors.initials: M
authors.lastname: Imeneo
authors.forename: Francesco
authors.initials: F
authors.lastname: Luzza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D015153:Blotting, Western; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000378:metabolism*; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: C508598:IL4 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020381:Interleukin-17; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: H. pylori-associated gastritis; Indoleamine 2,3-dioxygenase; Interferon-γ; Interleukin-4; Mucosal immunity