Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury

Abstract

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.

Neutrophils Do Not Mediate the Pathophysiological Sequelae of Cryptosporidium parvum Infection in Neonatal Piglets

“…This may be attributed to a paucity of neutrophil activational factors released as a consequence of the minimally invasive infection. For example, in studies of transgenic mice, the induced expression of interleukin-8 by intestinal epithelium is alone sufficient to recruit neutrophils into intestinal mucosa; however, they do not become activated or result in intestinal injury (20). Results of the present study do not identify the cellular source of peroxidative injury in C. parvum infection, although activated macrophages are a likely possibility.…”

Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis

“…33 It was also remarkable that rectal administration of L. reuteri ATCC55730 was accompanied by decreased expression of IL-8, a chemokine involved in chemoattraction of polymorphonuclear cells and thought to be a main mediator in the innate immune system response. 34 Indeed, an overexpression of chemokine axis components, including IL-8, has been described in inflamed colonic tissue of paediatric and adult IBD patients. 35 Our results are in agreement with observations in cultured epithelial cells that different L. reuteri strains and other Lactobacillus species can reduce over-expression of IL-8 due to proinflammatory triggers.…”

G Protein-Coupled Receptor 43 Is Essential for Neutrophil Recruitment during Intestinal Inflammation

“…Impaired epithelial permeability and loss of the integrity of the primary immunological barrier may lead to an increase of physiological and pathogenic bacteria and their components, which in turn may trigger intestinal inflammation (8). A pathological hallmark of active IBD is a strong migration of neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) into the mucosa, which can be characteristically found in the lamina propria and in the epithelial layer in IBD patients (9,10).…”