Administration of interleukin-1 receptor antagonist ameliorates renal ischemia-reperfusion injury.
Interleukin (IL)-1 is a major contributor to inflammation and apoptosis during ischemia/reperfusion (I/R) injury. Its deleterious effects are primarily mediated by the activation of nuclear factor-kappaB (NF-kappaB). Receptor-binding and signaling of IL-1 can be blocked by the IL-1 receptor antagonist (IL-1ra). The aim of our study was to characterize effects and mechanisms of IL-1ra administration on inflammation, apoptosis, and infiltration in renal I/R injury. Renal ischemia was induced in Lewis rats by clamping of the left renal artery for 45 min. Kidneys were removed for histological and molecular analysis 24 h or 5 days after reperfusion. IL-1ra ameliorated I/R induced renal injury and inflammation. Furthermore, the number of apoptotic tubular cells was lower in IL-1ra-treated animals 24 h after ischemia, which was paralleled by a Bax/Bcl-2 mRNA ratio towards anti-apoptotic effects. IL-1ra reduced the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA at 24 h and 5 days and that of intracellular adhesion molecule-1 (ICAM-1) expression at 24 h in the ischemic reperfused kidneys. Our results indicate that IL-1ra treatment ameliorates renal I/R injury and this protective effect might be mediated by reduced induction of NF-kappaB mediated MCP-1, ICAM-1, and a decreased ratio between Bax and Bcl-2 mRNA expression.
Rusai
Krisztina
K
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Huang
Hai
H
Sayed
Nora
N
Strobl
Matthias
M
Roos
Marcel
M
Schmaderer
Christoph
C
Heemann
Uwe
U
Lutz
Jens
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D018932:Chemokine CCL2 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein / Q000235:genetics
C494828:Bax protein, rat; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D017931:DNA Primers; D053590:Interleukin 1 Receptor Antagonist Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D018799:Intercellular Adhesion Molecule-1