IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa |
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Authors: | Caruso Roberta Fina Daniele Paoluzi Omero Alessandro Del Vecchio Blanco Giovanna Stolfi Carmine Rizzo Angelamaria Caprioli Flavio Sarra Massimiliano Andrei Fabio Fantini Massimo Claudio MacDonald Thomas T Pallone Francesco Monteleone Giovanni |
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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. |
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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. |
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Keywords: | Helicobacter pylori IL‐17 IL‐23 |
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