title: IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa.
abstract: Helicobacter pylori (Hp) infection is associated with a marked infiltration of the gastric mucosa by inflammatory cells. The molecular pathways that control Hp-associated inflammatory reaction are complex, but locally induced cytokines seem to contribute to maintaining the ongoing inflammation. We have previously shown that IL-17 is over-produced in Hp-infected gastric mucosa, and that IL-17 stimulates the synthesis of IL-8, the major neutrophil chemoattractant. Factors/mechanisms that regulate IL-17 expression remain, however, unknown. In this study, we initially expanded our previous data, showing that CD4(+) and CD8(+) T cells are a source of IL-17 in Hp-infected samples. Since IL-23 enhances T cell-derived IL-17 during bacterial infections, we then assessed the role of IL-23 in controlling IL-17 expression in Hp-colonized stomach. Using real-time PCR and ELISA, IL-23 was detected in all gastric biopsies, but its expression was more pronounced in Hp-infected samples in comparison to controls. Treatment of normal gastric lamina propria mononuclear cells (LPMC) with IL-23 enhanced Stat3 activation and IL-17 secretion, and pharmacological inhibition of Stat3 prevented IL-23-driven IL-17 synthesis. Consistently, blockade of IL-23 in cultures of LPMC from Hp-infected patients reduced Stat3 activation and IL-17 production. Data show that IL-23 is overexpressed in Hp-infected gastric mucosa where it could contribute to sustaining IL-17 production.
authors.affiliation: Department of Internal Medicine and Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, University Tor Vergata of Rome, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.forename: Daniele
authors.initials: D
authors.lastname: Fina
authors.forename: Omero Alessandro
authors.initials: OA
authors.lastname: Paoluzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Vecchio Blanco
authors.forename: Carmine
authors.initials: C
authors.lastname: Stolfi
authors.forename: Angelamaria
authors.initials: A
authors.lastname: Rizzo
authors.forename: Flavio
authors.initials: F
authors.lastname: Caprioli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Sarra
authors.forename: Fabio
authors.initials: F
authors.lastname: Andrei
authors.forename: Massimo Claudio
authors.initials: MC
authors.lastname: Fantini
authors.forename: Thomas T
authors.initials: TT
authors.lastname: MacDonald
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D053759:Interleukin-23 / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23