Interleukin-23A is associated with tumor growth in Helicobacter-pylori-related human gastric cancer

Background: Interleukin (IL)-23 is one of the newly identified inflammatory cytokines, and inflammation is also known to be related to the development of gastric cancer (GC). The role of IL-23 in gastric cancer, however, is largely unknown. In the present study, we investigated the expression and possible role of IL-23A in human GC. Methods: The expression of IL-23A and IL-17A in human GC tissues was determined by immunohistochemistry, and the relationship between IL-23A expression and clinical characteristics of GC was investigated. The serum concentration of IL-23A and IL-17A was also tested by ELISA. The source and role of IL-23A in GC were studied in vitro by Flowcytometry, MTS (Owen's reagent) assay and Western blot. Results: IL-23A, IL-23 receptor (IL-23R) and IL-17A were all overexpressed in human GC tissues, and the level of IL-23A was well correlated with IL-17A in GC tissues as well as in patient's serum. Macrophages and GC cells were the main source of IL-23A secretion upon stimulation of H. pylori lysate. Furthermore, we found that IL-23A promoted proliferation of GC cell lines via IL-17A/IL-17 receptor antagonist (IL-17RA)/nuclear factor-kappa B (NF-kappa B) signaling. Conclusions: The high expression of IL-23A is associated with GC. IL-23A can promoted GC cells growth by inducing the secretion of IL-17A in tumor microenvironment. Our results suggest that the serum concentration of IL-23A is a good biomarker of poor clinical prognosis in GC patients.