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Overexpression of Interleukin-1β Induces Gastric Inflammation and Cancer and Mobilizes Myeloid-Derived Suppressor Cells in Mice

2008; Cell Press; Volume: 14; Issue: 5 Linguagem: Inglês

10.1016/j.ccr.2008.10.011

1878-3686

Shuiping Tu, Govind Bhagat, Guanglin Cui, Shigeo Takaishi, Evelyn A. Kurt‐Jones, Barry Rickman, Kelly S. Betz, Melitta Penz-Oesterreicher, Olle Björkdahl, James G. Fox, Timothy C. Wang,

Immune cells in cancer

Polymorphisms of interleukin-1β (IL-1β) are associated with an increased risk of solid malignancies. Here, we show that stomach-specific expression of human IL-1β in transgenic mice leads to spontaneous gastric inflammation and cancer that correlate with early recruitment of myeloid-derived suppressor cells (MDSCs) to the stomach. IL-1β activates MDSCs in vitro and in vivo through an IL-1RI/NF-κB pathway. IL-1β transgenic mice deficient in T and B lymphocytes develop gastric dysplasia accompanied by a marked increase in MDSCs in the stomach. Antagonism of IL-1 receptor signaling inhibits the development of gastric preneoplasia and suppresses MDSC mobilization. These results demonstrate that pathologic elevation of a single proinflammatory cytokine may be sufficient to induce neoplasia and provide a direct link between IL-1β, MDSCs, and carcinogenesis.