title: Helicobacter pylori infection associates with a mucosal downregulation of ghrelin, negative regulator of Th1-cell responses.
abstract: BACKGROUND
  Helicobacter pylori (Hp)-related gastritis is characterized by a predominant T helper (Th)1/Th17 cell immunity. Ghrelin (GR) has immunoregulatory properties and inhibits experimental Th cell-dependent pathology.
  
  
  OBJECTIVE
  To evaluate whether Hp infection associates with changes in GR expression and whether GR negatively regulates Th1/Th17 cytokines during Hp infection.
  
  
  METHODS
  GR expression was evaluated by real-time PCR in gastric biopsies taken from Hp-infected and Hp-uninfected patients and in gastric biopsies of Hp-negative subjects cultured with or without H. pylori culture supernatant. To examine whether GR regulates Hp-induced cytokine production, H. pylori-infected gastric biopsies were stimulated with GR, and interleukin (IL)-12, interferon (IFN)-γ and IL-4 transcripts were evaluated by real-time PCR. IL-12 and IFN-γ were also analyzed in lamina propria mononuclear cells (LPMCs) extracted from Hp-infected gastric biopsies and cultured with GR.
  
  
  RESULTS
  GR RNA transcripts were reduced in biopsies from Hp-infected patients. Treatment of Hp-negative gastric biopsies with Hp culture supernatant reduced GR RNA expression. GR dose-dependently inhibited RNA expression of IL-12 and IFN-γ but not IL-4 in ex vivo cultures of mucosal explants and in cultures of gastric LPMCs from Hp-positive patients.
  
  
  CONCLUSIONS
  GR is downregulated in the gastric mucosa of H. pylori-infected patients. Such a defect could contribute to sustain the ongoing Th1-cell response.
authors.affiliation: Department of System Medicine, University of Rome "Tor Vergata", Viale Oxford 81, Rome, 00133, Italy.
authors.forename: Omero Alessandro
authors.initials: OA
authors.lastname: Paoluzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Vecchio Blanco
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.forename: Ivan
authors.initials: I
authors.lastname: Monteleone
authors.forename: Flavio
authors.initials: F
authors.lastname: Caprioli
authors.forename: Manfredi
authors.initials: M
authors.lastname: Tesauro
authors.forename: Mario
authors.initials: M
authors.lastname: Turriziani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallone
mesh_terms: D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology*; D054439:Ghrelin / Q000235:genetics* / Q000276:immunology; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D054439:Ghrelin; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: Gastritis; Helicobacter pylori; Th1 cells; ghrelin