Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis.

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.

Interleukin 13 receptors as biochemical markers in atopic patients.

BACKGROUND: Interleukin (IL) 13, a type 2 helper T cell (T(H)2), is an important regulator of inflammatory immune responses. It mediates its action through a receptor complex consisting of IL-13Ralpha1 and IL-4Ralpha. IL-13Ralpha2 binds IL-13 with high affinity and is thought to act primarily as a decoy receptor, sequestering IL-13 and thus inhibiting its action. Our aim was to clarify the role of these receptors in the diagnosis and follow-up of atopic patients. METHODS: We genotyped the 1398A>G polymorphism in the IL-13Ralpha1 gene using restriction fragment length polymorphism for causal genetic diversity and measured serum levels of IL-13Ralpha2 in 105 atopic patients suffering from atopic asthma, atopic dermatitis, and atopic rhinitis (35 each). We compared the results with those of 35 nonatopic control individuals. Total immunoglobulin (Ig) E and serum IL-13Ralpha2 were measured using enzyme-linked immunosorbent assay, and the eosinophil counts were recorded. RESULTS: A significant increase in serum IL-13Ralpha2 levels was recorded in the 3 atopic groups compared with the control group (P < .001), as well as a significant increase in total IgE levels and eosinophil counts. No significant association was found between 1398A>G and atopy other than a suggestive association between this polymorphism and raised total serum IgE levels in all 3 atopic groups (P < .001). CONCLUSIONS: These findings indicate that IL-13Ralpha2 plays an important role in atopy and that increased levels in different groups highlight its regulatory role in the development of atopic symptoms. The 1398A>G polymorphism might be involved in the production of IgE.