RT Journal Article
SR Electronic
T1 Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1565
OP 1572
DO 10.1136/gut.2004.061168
VO 54
IS 11
A1 T Kucharzik
A1 J T Hudson III
A1 A Lügering
A1 J A Abbas
A1 M Bettini
A1 J G Lake
A1 M E Evans
A1 T R Ziegler
A1 D Merlin
A1 J L Madara
A1 I R Williams
YR 2005
UL http://gut.bmj.com/content/54/11/1565.abstract
AB 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.