1 Role of IL-17A in the development of colitis-associated cancer

ow nloaded from 2Abstract A close relationship between inflammation and colon cancer has been widely accepted, and Interleukin (IL)-17A plays an important role in controlling colonic inflammation. However, the role of IL-17A has not yet been validated in colitis-associated cancer (CAC). This study aims to identify the effects of IL-17A in tumorigenesis utilizing IL-17A deficient mice in an experimental CAC model. CAC was induced in both the IL-17A deficient and C57BL/6 (WT) mice by injection of 12.5 mg/kg azoxymethane followed by three rounds of 1.7 % dextran sodium sulfate exposure to elicit colitis. On day 63 after the start of the study, mice were sacrificed. Colonic inflammation, proliferation and tumorigenesis were evaluated. Tumor numbers per mouse (1.43 vs. 5.80; p=0.02) and mean tumor size (1.17 mm vs. 3.58 mm; p=0.01) were significantly decreased in IL-17A deficient mice compared to WT mice. Furthermore, the inflammation and the proliferation scores of IL-17A deficient mice were significantly lower than WT mice. In the analysis of inflammatory mediators, IL-6, IFN-γ, TNF-α, and IL-17A were markedly decreased in IL-17A deficient mice compared to WT mice. In th