Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa

Helicobacter pylori (Hp)-associated gastritis is characterized by an increa sed 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 inflammato ry response. Factors/mechanisms that regulate IL-8 induction are, however, not fully understood. In the present study we investigated whether Hp infec tion is associated vith an increased production of IL-17,a T cell-derived c ytokine 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 whol e gastric mucosal and lamina propria mononuclear cell samples from Hp-infec ted patients than in those from uninfected subjects. Hp eradication was ass ociated 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-g secretion, indicatin g 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 polymorphonucl ear leukocyte migration, This effect was inhibitable by a neutralizing IL-8 but not IL-17 Ab, Together, these data indicate that biologically active I L-17 production is increased during Hp infection, suggesting the possibilit y that this cytokine may play an important role in the inflammatory respons e to the Ag colonization.