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

Dorothy Rocourt, Veela B. Mehta, Gail E. Besner

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background: Intestinal ischemia/reperfusion (I/R) injury is believed to be the major initiator of the systemic inflammatory response syndrome. As a result of intestinal I/R, the gut becomes a major source of inflammatory cytokine production. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) is cytoprotective after intestinal I/R and down-regulates pro-inflammatory cytokine production in vitro. We now examine the effects of HB-EGF on pro-inflammatory cytokine expression in vivo. Materials and methods: Rats were randomized into three groups: sham-operated, superior mesenteric artery occlusion (SMAO) for 90 min followed by 8 h of reperfusion (I/R), and I/R with intraluminal administration of HB-EGF 25 min after the initiation of ischemia (I/R + HB-EGF). Serum was drawn at 2, 4, 6, and 8 h post reperfusion for determination of cytokine protein levels using a bioplex suspension array system. Additional animals underwent the same ischemic protocol followed by 30 and 60 min of reperfusion with harvesting of ileal mucosa. Ileal pro-inflammatory cytokine gene expression was determined using reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for TNF-α, IL-6, and IL-1β. Results: HB-EGF decreased TNF-α, IL-6, and IL-1β serum protein levels at 4, 6, and 8 h after intestinal I/R injury. In addition, HB-EGF decreased local intestinal mucosal mRNA expression of TNF-α, IL-6, and IL-1β 30 and 60 min after intestinal injury. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)269-273
Number of pages5
JournalJournal of Surgical Research
Volume139
Issue number2
DOIs
StatePublished - May 15 2007

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Reperfusion Injury
Reperfusion
Cytokines
Ischemia
Interleukin-1
Interleukin-6
Heparin-binding EGF-like Growth Factor
Systemic Inflammatory Response Syndrome
Superior Mesenteric Artery
Reverse Transcriptase Polymerase Chain Reaction
Blood Proteins
Suspensions
Mucous Membrane
Down-Regulation
Gene Expression
Messenger RNA
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

@article{583d9e5f68c2494aa947922ae899584f,
title = "Heparin-Binding EGF-like Growth Factor Decreases Inflammatory Cytokine Expression After Intestinal Ischemia/Reperfusion Injury",
abstract = "Background: Intestinal ischemia/reperfusion (I/R) injury is believed to be the major initiator of the systemic inflammatory response syndrome. As a result of intestinal I/R, the gut becomes a major source of inflammatory cytokine production. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) is cytoprotective after intestinal I/R and down-regulates pro-inflammatory cytokine production in vitro. We now examine the effects of HB-EGF on pro-inflammatory cytokine expression in vivo. Materials and methods: Rats were randomized into three groups: sham-operated, superior mesenteric artery occlusion (SMAO) for 90 min followed by 8 h of reperfusion (I/R), and I/R with intraluminal administration of HB-EGF 25 min after the initiation of ischemia (I/R + HB-EGF). Serum was drawn at 2, 4, 6, and 8 h post reperfusion for determination of cytokine protein levels using a bioplex suspension array system. Additional animals underwent the same ischemic protocol followed by 30 and 60 min of reperfusion with harvesting of ileal mucosa. Ileal pro-inflammatory cytokine gene expression was determined using reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for TNF-α, IL-6, and IL-1β. Results: HB-EGF decreased TNF-α, IL-6, and IL-1β serum protein levels at 4, 6, and 8 h after intestinal I/R injury. In addition, HB-EGF decreased local intestinal mucosal mRNA expression of TNF-α, IL-6, and IL-1β 30 and 60 min after intestinal injury. Conclusions: 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.",
author = "Dorothy Rocourt and Mehta, {Veela B.} and Besner, {Gail E.}",
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Heparin-Binding EGF-like Growth Factor Decreases Inflammatory Cytokine Expression After Intestinal Ischemia/Reperfusion Injury. / Rocourt, Dorothy; Mehta, Veela B.; Besner, Gail E.

In: Journal of Surgical Research, Vol. 139, No. 2, 15.05.2007, p. 269-273.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Heparin-Binding EGF-like Growth Factor Decreases Inflammatory Cytokine Expression After Intestinal Ischemia/Reperfusion Injury

AU - Rocourt, Dorothy

AU - Mehta, Veela B.

AU - Besner, Gail E.

PY - 2007/5/15

Y1 - 2007/5/15

N2 - Background: Intestinal ischemia/reperfusion (I/R) injury is believed to be the major initiator of the systemic inflammatory response syndrome. As a result of intestinal I/R, the gut becomes a major source of inflammatory cytokine production. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) is cytoprotective after intestinal I/R and down-regulates pro-inflammatory cytokine production in vitro. We now examine the effects of HB-EGF on pro-inflammatory cytokine expression in vivo. Materials and methods: Rats were randomized into three groups: sham-operated, superior mesenteric artery occlusion (SMAO) for 90 min followed by 8 h of reperfusion (I/R), and I/R with intraluminal administration of HB-EGF 25 min after the initiation of ischemia (I/R + HB-EGF). Serum was drawn at 2, 4, 6, and 8 h post reperfusion for determination of cytokine protein levels using a bioplex suspension array system. Additional animals underwent the same ischemic protocol followed by 30 and 60 min of reperfusion with harvesting of ileal mucosa. Ileal pro-inflammatory cytokine gene expression was determined using reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for TNF-α, IL-6, and IL-1β. Results: HB-EGF decreased TNF-α, IL-6, and IL-1β serum protein levels at 4, 6, and 8 h after intestinal I/R injury. In addition, HB-EGF decreased local intestinal mucosal mRNA expression of TNF-α, IL-6, and IL-1β 30 and 60 min after intestinal injury. Conclusions: 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.

AB - Background: Intestinal ischemia/reperfusion (I/R) injury is believed to be the major initiator of the systemic inflammatory response syndrome. As a result of intestinal I/R, the gut becomes a major source of inflammatory cytokine production. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) is cytoprotective after intestinal I/R and down-regulates pro-inflammatory cytokine production in vitro. We now examine the effects of HB-EGF on pro-inflammatory cytokine expression in vivo. Materials and methods: Rats were randomized into three groups: sham-operated, superior mesenteric artery occlusion (SMAO) for 90 min followed by 8 h of reperfusion (I/R), and I/R with intraluminal administration of HB-EGF 25 min after the initiation of ischemia (I/R + HB-EGF). Serum was drawn at 2, 4, 6, and 8 h post reperfusion for determination of cytokine protein levels using a bioplex suspension array system. Additional animals underwent the same ischemic protocol followed by 30 and 60 min of reperfusion with harvesting of ileal mucosa. Ileal pro-inflammatory cytokine gene expression was determined using reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for TNF-α, IL-6, and IL-1β. Results: HB-EGF decreased TNF-α, IL-6, and IL-1β serum protein levels at 4, 6, and 8 h after intestinal I/R injury. In addition, HB-EGF decreased local intestinal mucosal mRNA expression of TNF-α, IL-6, and IL-1β 30 and 60 min after intestinal injury. Conclusions: 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.

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