Interleukin-17C in Human Helicobacter pylori Gastritis

Abstract

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 of <i>Helicobacter pylori</i>-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in <i>H. pylori</i>-infected and uninfected gastric biopsy specimens. <i>IL-17C</i> mRNA was upregulated approximately 4.5-fold in <i>H. pylori</i>-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 in <i>H. pylori</i>-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. <i>IL-17C</i> mRNA levels were also significantly greater among <i>cagA</i>-positive than <i>cagA</i>-negative <i>H. pylori</i> infections (<i>P</i> = 0.012). <i>In vitro</i> studies confirmed an increase in <i>IL-17C</i> mRNA and protein levels in cells infected with <i>cagA</i>-positive infections compared to cells infected with either <i>cagA</i>-negative or <i>cag</i> pathogenicity 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, <i>H. pylori</i> infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of <i>H. pylori</i>-induced diseases remains to be determined.