Western‐style diets induce macrophage infiltration and contribute to colitis‐associated carcinogenesis

Abstract

A Western-style diet (WD) is known to play an important role in inflammatory bowel disease and colon carcinogenesis. The purpose of this study was to understand the role of macrophages in WD-induced colitis associated with carcinogenesis. Male BALB/c mice were fed a WD or a control diet (CD) for 4 weeks and exposed to azoxymethane (AOM) followed by 2% dextran sulfate sodium (DSS) for 7 days. The WD increased susceptibility to DSS-induced inflammation and accelerated the infiltration of macrophages. The incidence and multiplicity of colon tumors were higher in mice fed the WD than in those fed the CD (P < 0.05). Levels of prostaglandin-endoperoxide synthase (PTGS) 2 and prostaglandin (PG) E(2) in the colon were higher after treatment with AOM and DSS in mice fed the WD than in those fed the CD. In addition, WD consumption increased the DNA binding activity of nuclear factor-kappaB and the serum concentration of tumor necrosis factor (TNF)-α. Mice fed the WD had higher numbers of F4/80-positive cells surrounding cancer cells compared with mice fed the CD. These cells expressed PTGS2, TNF-α and β-catenin, which are up-regulated by the WD. We also found that the WD increased unphosphorylated β-catenin accumulation in the cytoplasm and nucleus of colon cancer cells. A WD increases the susceptibility to DSS-induced inflammation and accelerates the infiltration of macrophages. In turn, this resulted in the development and progression of colon cancer.