Author/Authors :
Tu، نويسنده , , Shuiping and Bhagat، نويسنده , , Govind and Cui، نويسنده , , Guanglin and Takaishi، نويسنده , , Shigeo and Kurt-Jones، نويسنده , , Evelyn A. and Rickman، نويسنده , , Barry and Betz، نويسنده , , Kelly S. and Penz-Oesterreicher، نويسنده , , Melitta and Bjorkdahl، نويسنده , , Olle and Fox، نويسنده , , James G. and Wang، نويسنده , , Timothy C.، نويسنده ,
Abstract :
Summary
rphisms 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.
