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Heparin-binding EGF-like growth factor decreases inflammatory cytokine expression after intestinal ischemia/reperfusion injury.
- Source :
-
The Journal of surgical research [J Surg Res] 2007 May 15; Vol. 139 (2), pp. 269-73. Date of Electronic Publication: 2007 Feb 07. - Publication Year :
- 2007
-
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.<br />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-alpha, IL-6, and IL-1beta.<br />Results: HB-EGF decreased TNF-alpha, IL-6, and IL-1beta 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-alpha, IL-6, and IL-1beta 30 and 60 min after intestinal injury.<br />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.
- Subjects :
- Animals
Heparin-binding EGF-like Growth Factor
Intercellular Signaling Peptides and Proteins
Interleukin-1beta antagonists & inhibitors
Interleukin-1beta blood
Interleukin-1beta genetics
Interleukin-6 antagonists & inhibitors
Interleukin-6 blood
Interleukin-6 genetics
Intestinal Mucosa metabolism
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Tumor Necrosis Factor-alpha antagonists & inhibitors
Tumor Necrosis Factor-alpha blood
Tumor Necrosis Factor-alpha genetics
Cytokines antagonists & inhibitors
Epidermal Growth Factor pharmacology
Inflammation Mediators antagonists & inhibitors
Intestines blood supply
Reperfusion Injury metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-4804
- Volume :
- 139
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of surgical research
- Publication Type :
- Academic Journal
- Accession number :
- 17291530
- Full Text :
- https://doi.org/10.1016/j.jss.2006.10.047