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Cancer Cell. 2008 Nov 4;14(5):408-19. doi: 10.1016/j.ccr.2008.10.011.

Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice.

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1
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Erratum in

  • Cancer Cell. 2008 Dec 9;14(6):494.
  • Cancer Cell. 2011 Jan 18;19(1):154.

Abstract

Polymorphisms of interleukin-1beta (IL-1beta) are associated with an increased risk of solid malignancies. Here, we show that stomach-specific expression of human IL-1beta 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-1beta activates MDSCs in vitro and in vivo through an IL-1RI/NF-kappaB pathway. IL-1beta 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-1beta, MDSCs, and carcinogenesis.

PMID:
18977329
PMCID:
PMC2586894
DOI:
10.1016/j.ccr.2008.10.011
[Indexed for MEDLINE]
Free PMC Article

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