Infection, inflammation and colon carcinogenesis

Abstract

The importance of chronic inflammation as a risk factor for major cancers is well documented [1], and the inflammatory state is known to involve contributions of both adaptive and innate immune components. In a recent publication [2] we describe an experimental animal model in which infection, inflammation and cancer are mechanistically linked, and provide evidence that chemical mediators of the innate immune system and bacterial toxins both play key roles in driving colon carcinogenesis. In this model, epithelial injury caused by Helicobacter hepaticus infection enhances access of bacterially-associated products to pattern-recognition receptors located on surfaces of macrophages and dendritic cells. Receptor ligation leads to activation of transcription factors, including NF-kappa B, that regulate production of chemo-attractants for macrophages and neutrophils, recruitment of which is a hallmark of inflammation. These acute inflammatory events are re-enforced by expression of powerful inflammatory mediators such as TNF-α and IL-2, which amplify acute inflammatory gene expression and enhance cell survival. If not properly extinguished, the innate inflammatory response is maintained and further amplified by activation of cell-mediated adaptive immunity.