Back to Search
Start Over
Interleukin 18 causes hepatic ischemia/reperfusion injury by suppressing anti-inflammatory cytokine expression in mice
- Source :
- Hepatology (Baltimore, Md.). 39(3)
- Publication Year :
- 2004
-
Abstract
- Hepatic ischemia/reperfusion injury is a clinically important problem. While the mechanisms of the initial event and subsequent neutrophil-dependent injury are somewhat understood, little is known about the regulation of endogenous hepatoprotective effects on this injury. Interleukin 12 (IL-12) plays a role in the induction of this injury, but involvement of interleukin 18 (IL-18) has not been clarified. Using a murine model of partial hepatic ischemia and subsequent reperfusion, the aim of the current study was to determine whether IL-18 is up-regulated during hepatic ischemia/reperfusion and to determine the role of endogenous IL-18 in the development and regulation of inflammatory hepatic ischemia/reperfusion injury. Hepatic IL-18 expression was up-regulated from 1 to 8 hours after reperfusion. Hepatic ischemia/reperfusion induced nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) activation, as defined by electrophoretic mobility shift assay, and caused significant increases in liver neutrophil recruitment, apoptosis, hepatocellular injury, and liver edema as defined by liver myeloperoxidase content, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining, serum aminotransferase levels, and liver wet-to-dry weight ratios. In mice treated with neutralizing antibody to IL-18, ischemia/reperfusion-induced increases in CXC chemokine expression, activation of NF-kappaB and AP-1, and apoptosis were greatly reduced. Furthermore, under blockade of IL-18, anti-inflammatory cytokines such as IL-4 and IL-10 were greatly up-regulated. Signal transducer and activator of transcription 6 (STAT6) was significantly activated under blockade of IL-18. These conditions also caused significant reduction in liver neutrophil sequestration and liver injury. In conclusion, the data suggest that IL-18 is required for facilitating neutrophil-dependent hepatic ischemia/reperfusion injury through suppressing anti-inflammatory cytokine expression.
- Subjects :
- Male
Ischemia
Apoptosis
Pharmacology
Mice
Medicine
Animals
Interleukin 4
Liver injury
TUNEL assay
Hepatology
biology
business.industry
Interleukin-18
NF-kappa B
medicine.disease
Interleukin-10
Mice, Inbred C57BL
Transcription Factor AP-1
Interleukin 10
Liver
Neutrophil Infiltration
Myeloperoxidase
Chemokines, CC
Reperfusion Injury
Immunology
biology.protein
Trans-Activators
Interleukin 18
Interleukin-4
business
STAT6 Transcription Factor
Reperfusion injury
Chemokines, CXC
Liver Circulation
Subjects
Details
- ISSN :
- 02709139
- Volume :
- 39
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Hepatology (Baltimore, Md.)
- Accession number :
- edsair.doi.dedup.....522f20b46cd9ef46ed841da1ab31c650