Heparin-Binding EGF-like Growth Factor Decreases Inflammatory Cytokine Expression After Intestinal Ischemia/Reperfusion Injury

Abstract

We conclude that pro-inflammatory cytokine expression is increased both locally and in the systemic circulation after intestinal I/R and that the administration of HB-EGF significantly reduces intestinal I/R-induced pro-inflammatory cytokine expression in vivo.

Decay-Accelerating Factor Attenuates C-Reactive Protein-Potentiated Tissue Injury After Mesenteric Ischemia/Reperfusion

“…This was Mesenteric IR causes local and systemic inflammatory derangements, including release of pro-inflammatory cytokines, and is associated with complement activation. Reports indicate the intestine is a source of cytokine production following intestinal IR injury [31,32]. In the present study, IL-6 release was found not only in local intestinal tissue, but also in remote lung tissue.…”

Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis

“…This is especially true since oral administration of EGF has been shown to reduce bacterial colonization of the intestinal epithelium by Campylobacter jejuni in an animal model of bacterial enteritis (36). Additionally, intraluminal administration of heparin-binding EGF, an EGF family member, decreases systemic proinflammatory cytokine levels following ischemia-reperfusion injury (44). However, intestine-specific overexpression of EGF had minimal impact on both bacterial burden and cytokine levels following CLP in both blood and the peritoneal cavity.…”

Heparin-Binding EGF-like Growth Factor Decreases Neutrophil–Endothelial Cell Interactions

“…We have also shown that HB-EGF decreases ROS production in activated leukocytes in vitro and in intestine subjected to I/R injury in vivo [13]. We showed that HB-EGF decreases IL-8 production in cytokine-stimulated intestinal epithelial cells [14], important since IL-8 is a potent chemotactic factor and activator of neutrophils, and that HB-EGF decreases the production of the proinflammatory cytokines TNF-␣, IL-6, and IL1-␤ after intestinal I/R injury [15]. We hypothesize that the beneficial effects of HB-EGF after intestinal I/R injury may be due, in part, to its ability to decrease PMN-EC adhesion and PMN endothelial transmigration.…”

“…We previously found that treatment with HB-EGF decreased ROS production [13] and proinflammatory cytokine production [15] in injured intestine after intestinal I/R. In the complex in vivo environment, it is difficult to determine whether the ability of HB-EGF to decrease inflammatory cell infiltration and injurious mediator production after intestinal injury is simply a result of its ability to directly protect the mucosa from injury (i.e., less necrotic tissue leads to less inflammatory cell infiltration), or whether this is a direct effect of HB-EGF on PMN and/or EC.…”