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

Changming Liu,Wei Zhu,Jie Zhan,Qijun Wan,Ying Zhang,Yuanyuan Zhao,Huiping Peng

doi:10.1186/s12935-014-0104-x

Abstract

BackgroundInterleukin (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.MethodsThe 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.ResultsIL-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-κB (NF-κB) signaling.ConclusionsThe 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.

Highlights

Interleukin (IL)-23 is one of the newly identified inflammatory cytokines, and inflammation is known to be related to the development of gastric cancer (GC)
IL-23A, IL-23 receptor (IL-23R) and IL-17A are excessive in human GC To investigate the expression of IL-23A and the related molecules in human GC, 141 paraffin-embedded tissues were studied for the expression and distribution of IL23A, IL-23R and IL-17A using immunohistochemistry
We observed that IL-23A, IL-23R and IL-17A were all significantly overexpressed in human GC compared to normal controls

Summary

Introduction

Interleukin (IL)-23 is one of the newly identified inflammatory cytokines, and inflammation is known to be related to the development of gastric cancer (GC). IL-23A is involved in the inflammatory response through promoting matrix metalloprotease 9, increasing angiogenesis and reducing CD8+ T cells infiltration [3,4]. Th17 cells secrete proinflammatory cytokine IL-17A that can induce Th17 response by stimulating the production of other proinflammatory molecules such as IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and chemokines, resulting in inflammation. A genome-wide association study has revealed that −197G > A polymorphism at position −197 in the IL-17 promoter region significantly increased GC risk in the general population [10,11], while increased expression of IL-17 was found in patients with GC. Persistent inflammation induced in part by IL-17 may contribute to gastric mucosal pathology, thereby increase the risk of GC [9,11,13]

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