A recent publication from A. Hertati et al. in the Frontiers in Pharmacology Journal demonstrated that an interleukin-4 receptor α subunit (IL-4Rα) deficiency alleviates intestinal inflammation in a mouse dextran sulfate sodium (DSS)-induced colitis model by enhancing intestinal mucosal barrier function as confirmed using Chondrex, Inc.’s FITC-Dextran.
In addition to nutrient absorption, the intestinal mucosa has barrier functions to prevent antigens and other unwanted intestinal substances from entering the circulatory system. These barriers work as physical barriers and chemical barriers and are regulated by intestinal environmental factors and cellular networks including epithelial cells, mesenchymal cells, immune cells, and neuronal cells. In addition, the intestinal mucosal barrier functions are regulated by the presence of IL-4 and IL-13. The role of IL-4Rα in intestinal mucosal inflammation was investigated using a DSS-induced colitis model in IL-4Rα-deficient (IL-4Rα-/-) mice.
IL-4Rα-/- mice of BALB/c background were treated with 3% DSS in their drinking water for seven days to induce experimental colitis. After an overnight fast, mice were orally administered FITC-dextran (4 kDa). Four hours later, plasma samples were taken and prepared for analysis. The fluorescence intensity of the plasma samples was measured in black 96-well plates using a microplate reader. The plasma FITC-dextran levels were markedly lower on day 7 in the IL-4Rα-/- colitis mice than in the wild-type colitis mice. Furthermore, the IL-4 activities in preventing leaky mucosa were investigated by evaluating NADPH Oxidase 1 (NOX1)-dependent reactive oxygen species production and neutrophil infiltration as well as IL-1beta, CXCL2, and NOX1 mRNA expression in the mucosa.
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1. A. Hertati, S. Hayashi, Y. Ogawa, T. Yamamoto, M. Kadowaki, Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function. Frontiers in Pharmacology. 11 (2020)
In order to study mucosal barrier function and the contribution of cytokines and chemokines to the pathogenesis of colitis models, Chondrex Inc. provides DSS for inducing mouse colitis, various probe-conjugated dextrans, and ELISA kits to determine cytokine and chemokine levels. Please refer to Chondrex, Inc’s website for more information.