Interleukin 23 and Tumor-Elicited Inflammation in Colitis-Associated and Spontaneous Colon Cancer

Abstract

Colitis associated cancer (CAC) is the most serious complication of inflammatory bowel diseases (IBD) and its pathogenesis is driven by inflammation. Cytokines are molecular mediators of inflammation. Cytokines like IL-6, IL-17 and IL-23 are upregulated not only in CAC tumors, but also in spontaneous colorectal cancer (CRC), where they regulate tumor-elicited inflammation. We use mouse models of CAC (azoxymethane+ DSS) and monoallelic inactivation of APC tumor suppressor gene in the colon only as a model of CRC. We found that due to the disruption of barriers during colitis or during CRC initiation commensal microflora activates expression of IL-23, which as a master regulator of tumor elicited inflammation controls the expression of other pro-tumorigenic cytokines such as IL-6, IL-11, IL-17 and IL-22. Inactivation of IL-23 or some of its downstream cytokines reduced tumor-elicited inflammation and decreased CAC and CRC development IL-23 is important for CAC and CRC tumorigenesis and regulates tumor -elicited inflammation