Interleukin-17C in Human Helicobacter pylori Gastritis

The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology ofHelicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed inH. pylori-infected and uninfected gastric biopsy specimens.IL-17CmRNA was upregulated approximately 4.5-fold inH. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression inH. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells.IL-17CmRNA levels were also significantly greater amongcagA-positive thancagA-negativeH. pyloriinfections (P= 0.012).In vitrostudies confirmed an increase inIL-17CmRNA and protein levels in cells infected withcagA-positive infections compared to cells infected with eithercagA-negative orcagpathogenicity island (PAI) mutant. Chemical inhibition of IκB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion,H. pyloriinfection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis ofH. pylori-induced diseases remains to be determined.