Neutrophil Migration across the Intestinal Epithelial Barrier – Summary of in vitro Data and Description of a New Transgenic Mouse Model with Doxycycline-Inducible Interleukin-8 Expression in Intestinal Epithelial Cells

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Abstract
The intestinal epithelium serves as a protective barrier between the gut lumen and the underlying mucosa. During intestinal inflammation in inflammatory bowel disease (IBD) there is increased paracellular permeability and strong migration of the neutrophils into the mucosa as well as transepithelial neutrophil migration with the formation of crypt abscesses. From in vitro data we know that neutrophil migration is triggered by epithelial-derived interleukin-8 (IL-8). A pathogen-elicited epithelial chemoattractant activity, which is released by intestinal epithelial cells from the apical surface, seems to be responsible for the final step in transepithelial migration. To mimic the pathophysiological situation with influx of neutrophils during IBD, a double transgenic mouse model with doxycycline-inducible IL-8 expression in intestinal epithelial cells was established. This model will allow to study the role of neutrophil influx during chronic intestinal inflammation. It will also provide insights into the mechanisms of neutrophil transepithelial migration.