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 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.
Luzza
F
F
Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro Magna Graecia, Catanzaro, Italy. luzza@unicz.it
Parrello
T
T
Monteleone
G
G
Sebkova
L
L
Romano
M
M
Zarrilli
R
R
Imeneo
M
M
Pallone
F
F
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000502:physiology; D000328:Adult; D000368:Aged; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000502:physiology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D000276:Adjuvants, Immunologic; D020381:Interleukin-17; D016209:Interleukin-8