INFLAMMATORY BOWEL DISEASE Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury
نویسندگان
چکیده
Aim: Neutrophil migration in the intestine depends on chemotaxis of neutrophils to CXC chemokines produced by epithelial cells. The goal of this project was to determine if acute induction of a CXC chemokine gradient originating from intestinal epithelial cells is sufficient to induce neutrophil influx into intact intestinal tissue. Methods and results: The authors developed a double transgenic mouse model with doxycycline induced human IL-8 expression restricted to intestinal epithelial cells. Doxycycline treatment of double transgenic mice for three days resulted in a 50-fold increase in the caecal IL-8 concentration and influx of neutrophils into the lamina propria. Although neutrophils entered the paracellular space between epithelial cells, complete transepithelial migration was not observed. Doxycycline treatment also increased the water content of the caecal and colonic stool, indicating dysfunctional water transport. However, the transmural electrical resistance was not decreased. Neutrophils recruited to the intestinal epithelium did not show evidence of degranulation and the epithelium remained intact as judged by histology. Conclusions: This conditional transgenic model of chemokine expression provides evidence that acute induction of IL-8 in the intestinal epithelium is sufficient to trigger neutrophil recruitment to the lamina propria, but additional activation signals are needed for full activation and degranulation of neutrophils, mucosal injury, and complete transepithelial migration.
منابع مشابه
Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury.
AIM Neutrophil migration in the intestine depends on chemotaxis of neutrophils to CXC chemokines produced by epithelial cells. The goal of this project was to determine if acute induction of a CXC chemokine gradient originating from intestinal epithelial cells is sufficient to induce neutrophil influx into intact intestinal tissue. METHODS AND RESULTS The authors developed a double transgenic...
متن کاملDecay-accelerating factor attenuates C-reactive protein-potentiated tissue injury after mesenteric ischemia/reperfusion.
BACKGROUND C-reactive protein (CRP) is an acute pro-inflammatory mediator that has been demonstrated to enhance ischemia/reperfusion (IR) injury by virtue of activating the complement system. CRP is able to interact with complement proteins such as C1q, complement factor H, and C4b-binding protein. Since complement activation is central in the expression of tissue injury following IR, we have i...
متن کاملNetrin-1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation
The intestinal epithelium is a dynamic barrier playing an active role in intestinal homeostasis and inflammation. Intestinal barrier function is dysregulated during inflammatory bowel disease (IBD), with epithelial cells playing a significant part in generating an inflammatory milieu through the release of signals that attract leukocytes to the intestinal lamina propria. However, it is increasi...
متن کاملInterferon ã induces diVerential upregulation of á and â chemokine secretion in colonic epithelial cell lines
Background—Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the á chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of â chemokines, which are preferentially involved in recruiting monocytes...
متن کاملCXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.
Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that kerati...
متن کامل