Secretory leukocyte protease inhibitor in mice regulates local and remote organ inflammatory injury induced by hepatic ischemia/reperfusion.
Gastroenterology
; 117(4): 953-61, 1999 Oct.
Article
in En
| MEDLINE
| ID: mdl-10500079
ABSTRACT
BACKGROUND & AIMS:
This study identified and characterized the hepatic expression of secretory leukocyte protease inhibitor (SLPI) during hepatic ischemia and reperfusion in mice. In addition, the effects of exogenously administered and endogenous SLPI on liver and lung injury induced by hepatic ischemia and reperfusion were evaluated.METHODS:
C57BL/6 mice underwent 90 minutes of partial hepatic ischemia and 4 hours of reperfusion in the presence or absence of exogenous SLPI or neutralizing antibodies to SLPI.RESULTS:
Intravenous infusion of SLPI reduced liver and lung damage and diminished neutrophil accumulation in both organs. These effects were accompanied by reduced serum levels of tumor necrosis factor (TNF)-alpha and the CXC chemokine macrophage inflammatory protein (MIP)-2. SLPI also suppressed activation of the transcription factor NF-kappaB in liver. Hepatic ischemia and reperfusion caused increased expression of SLPI messenger RNA and SLPI protein, which was found in hepatocytes. Treatment of mice with anti-SLPI enhanced serum levels of TNF-alpha and MIP-2 and increased hepatic neutrophil accumulation and amount of liver injury.CONCLUSIONS:
These data indicate that SLPI has protective effects against hepatic ischemia/reperfusion injury and suggest that endogenous SLPI functions to regulate the hepatic inflammatory response.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reperfusion Injury
/
Proteins
/
Inflammation
/
Ischemia
/
Liver Circulation
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Gastroenterology
Year:
1999
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA