PMID- 18363573 OWN - NLM STAT- MEDLINE DCOM- 20080801 LR - 20080501 IS - 0934-0874 (Print) IS - 0934-0874 (Linking) VI - 21 IP - 6 DP - 2008 Jun TI - Administration of interleukin-1 receptor antagonist ameliorates renal ischemia-reperfusion injury. PG - 572-80 LID - 10.1111/j.1432-2277.2008.00651.x [doi] AB - 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. FAU - Rusai, Krisztina AU - Rusai K AD - First Department of Pediatrics, Semmelweis University, Budapest, Hungary. FAU - Huang, Hai AU - Huang H FAU - Sayed, Nora AU - Sayed N FAU - Strobl, Matthias AU - Strobl M FAU - Roos, Marcel AU - Roos M FAU - Schmaderer, Christoph AU - Schmaderer C FAU - Heemann, Uwe AU - Heemann U FAU - Lutz, Jens AU - Lutz J LA - eng PT - Journal Article DEP - 20080318 PL - Switzerland TA - Transpl Int JT - Transplant international : official journal of the European Society for Organ Transplantation JID - 8908516 RN - 0 (Bax protein, rat) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (DNA Primers) RN - 0 (Interleukin 1 Receptor Antagonist Protein) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (bcl-2-Associated X Protein) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Base Sequence MH - Chemokine CCL2/genetics MH - DNA Primers/genetics MH - Intercellular Adhesion Molecule-1/genetics MH - Interleukin 1 Receptor Antagonist Protein/*administration & dosage MH - Kidney/blood supply/*drug effects/*injuries/pathology MH - Leukocytes/drug effects/pathology MH - Male MH - Proto-Oncogene Proteins c-bcl-2/genetics MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Inbred Lew MH - Recombinant Proteins/administration & dosage MH - Reperfusion Injury/genetics/pathology/*prevention & control MH - bcl-2-Associated X Protein/genetics EDAT- 2008/03/28 09:00 MHDA- 2008/08/02 09:00 CRDT- 2008/03/28 09:00 PHST- 2008/03/28 09:00 [pubmed] PHST- 2008/08/02 09:00 [medline] PHST- 2008/03/28 09:00 [entrez] AID - TRI651 [pii] AID - 10.1111/j.1432-2277.2008.00651.x [doi] PST - ppublish SO - Transpl Int. 2008 Jun;21(6):572-80. doi: 10.1111/j.1432-2277.2008.00651.x. Epub 2008 Mar 18.