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Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro Magna Graecia, Catanzaro, Italy;
Department of Pediatric Gastroenterology, St. Bartholomews and Royal London School of Medicine and Dentistry, London, United Kingdom;
Cattedra di Gastroenterologia, Seconda Università di Napoli, Naples, Italy;
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Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy; and
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Università di Roma Tor Vergata, Rome, Italy
Helicobacter pylori (Hp)-associated gastritis is characterized by an increased number of acute and chronic inflammatory cells secreting cytokines that contribute to maintain and expand the local inflammation. Locally induced IL-8 is believed to play a major role in the Hp-associated acute inflammatory response. Factors/mechanisms that regulate IL-8 induction are, however, not fully understood. In the present study we investigated whether Hp infection is associated with an increased production of IL-17, a T cell-derived cytokine capable of modulating IL-8 gene expression. We showed that both IL-17 RNA transcripts and protein were expressed at a higher level in the whole gastric mucosal and lamina propria mononuclear cell samples from Hp-infected patients than in those from uninfected subjects. Hp eradication was associated with a marked down-regulation of IL-17 expression. The addition of a neutralizing anti-IL-17 Ab to the gastric lamina propria mononuclear cell cultures resulted in a significant inhibition of IL-8 secretion, indicating that IL-17 contributes to enhance IL-8 in the Hp-colonized gastric mucosa. Consistently, stimulation of MKN 28 cells, a gastric epithelial cell line, with IL-17 increased IL-8 secretion. Finally, conditioned medium from the IL-17-stimulated MKN 28 cell cultures promoted the in vitro polymorphonuclear leukocyte migration. This effect was inhibitable by a neutralizing IL-8 but not IL-17 Ab. Together, these data indicate that biologically active IL-17 production is increased during Hp infection, suggesting the possibility that this cytokine may play an important role in the inflammatory response to the Hp colonization.
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