کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2107688 | 1083694 | 2008 | 12 صفحه PDF | دانلود رایگان |
SummaryPolymorphisms 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.
Journal: - Volume 14, Issue 5, 4 November 2008, Pages 408–419