IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa.
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.
Caruso
Roberta
R
Department of Internal Medicine and Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, University Tor Vergata of Rome, Rome, Italy.
Fina
Daniele
D
Paoluzi
Omero Alessandro
OA
Del Vecchio Blanco
Giovanna
G
Stolfi
Carmine
C
Rizzo
Angelamaria
A
Caprioli
Flavio
F
Sarra
Massimiliano
M
Andrei
Fabio
F
Fantini
Massimo Claudio
MC
MacDonald
Thomas T
TT
Pallone
Francesco
F
Monteleone
Giovanni
G
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
D020381:Interleukin-17; D053759:Interleukin-23