IL-1β mediates MCP-1 induction by Wnt5a in gastric cancer cells

BACKGROUND: Both Wnt5a overexpression and macrophage infiltration have been implicated in inflammation and cancer. The aim of this study is to reveal the involvement of Wnt5a in macrophage recruitment in gastric cancer. METHODS: mRNA expression in gastric cancer tissues and cells was investigated by real-time PCR. Protein secretion by gastric cancer cells was determined by ELISA. PcDNA3.1-Wnt5a expression vector and Wnt5a siRNA vector were used to overexpress and silence Wnt5a expression in gastric cells, respectively. Macrophage migration was analyzed by transwell, and macrophage cytoskeleton was stained with FITC-phalloidin. RESULTS: Wnt5a was overexpressed in gastric cancer tissues, and correlated with monocyte chemotactic protein 1 (MCP-1) and interleukin 1β (IL-1β), respectively. In gastric cancer cells, Wnt5a induced MCP-1 expression, which was mediated by IL-1β. Conditioned medium from gastric cancer cells transfected with Wnt5a stimulated macrophage chemotaxis and cytoskeletal changes via MCP-1, which were suppressed by recombinant IL-1 receptor antagonist (rIL-1Ra). CONCLUSIONS: These results suggest that Wnt5a is involved in macrophage recruitment by upregulating MCP-1, and IL-1Ra may be used to inhibit macrophage recruitment in gastric cancer.