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Titolo:
Lipopolysaccharide pretreatment protects from renal ischemia/reperfusion injury - Possible connection to an interleukin-6-dependent Pathway
Autore:
Heemann, U; Szabo, A; Hamar, P; Muller, V; Witzke, O; Lutz, J; Philipp, T;
Indirizzi:
Univ Essen Gesamthsch, Dept Nephrol, D-45122 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45122 hrol, D-45122 Essen, Germany Semmelweis Univ Med, H-1085 Budapest, Hungary Semmelweis Univ Med Budapest Hungary H-1085 ed, H-1085 Budapest, Hungary
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 1, volume: 156, anno: 2000,
pagine: 287 - 293
SICI:
0002-9440(200001)156:1<287:LPPFRI>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; ISCHEMIA-REPERFUSION INJURY; ENDOTOXIN PRETREATMENT; TOLERANCE; FAILURE; SEPSIS; CELLS; RAT; METABOLITES; NEUTROPHILS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Heemann, U Univ Essen Gesamthsch, NTP Ambulanz, Hufelandstr 55, D-45122 Essen, Germany Univ Essen Gesamthsch Hufelandstr 55 Essen Germany D-45122 any
Citazione:
U. Heemann et al., "Lipopolysaccharide pretreatment protects from renal ischemia/reperfusion injury - Possible connection to an interleukin-6-dependent Pathway", AM J PATH, 156(1), 2000, pp. 287-293

Abstract

In vivo administration of low doses of lipopolysaccharide (LPS) to rodentscan protect these animals from subsequently administrated, usually lethal doses of endotoxin or LPS. In this study we tested the effects of LPS pretreatment on ischemia/reperfusion injury in the kidney. Male C57/B1 mice werepretreated with different doses of LPS or phosphate-buffered saline on days -4 and -3. The right kidney was removed, and the vessels of the left kidney were clamped for 30 or 45 minutes on day 0. Creatinine levels and survival of animals were monitored. To test the involvement of cytokines, additional animals were harvested before ("time 0") and 15 minutes, 1, 2, 8, and 16 hours after reperfusion for histology, immunohistochemistry, terminal deoxynucleotidyl-transferase-mediated UTP end-labeling assay, and reverse transcriptase-polymerase chain reaction analysis (including tumor necrosis factor (TNF)-alpha, interleukin. (IL)-1, IL-6, inducible nitric oxide synthase (iNOS), and interferon (IFN)-gamma messenger RNA (mRNA)). In controls, renal ischemia of 30 minutes was nonlethal, whereas 73% of the animals died within 48 +/- 18 hours, after 45 minutes of ischemia. All different doses of LPS protected the animals from lethal renal ischemia/reperfusion injury. Starting at similar levels, serum creatinine increased significantly in controls but not in LPS-pretreated animals over time. As early as 2 hours after reperfusion, tubular cell damage was significantly more pronounced in controls than in LPS-treated mice. In controls, tubules deteriorated progressively until 8 hours of reperfusion. At this time, more than 50% of tubular cells were destroyed. This destruction was accompanied by a pronounced leukocytic infiltration, predominantly by macrophages. In contrast, LPS pretreatment prevented the destruction of kidney tissue and infiltration by leukocytes. The terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay revealed significantly more apoptotic cells in controls compared with LPS-pretreated animals. IL-1, IFN-gamma, and iNOS mRNA expression did not differbetween the groups throughout the time points examined. However, the expression of TNF-alpha mRNA was significantly increased at 2 hours and IL-6 mRNA was significantly down-regulated before ischemia and shortly after reperfusion in the LPS-pretreated kidneys. Therefore, me found that sublethal doses of LPS induced cross-tolerance to renal ischemia/reperfusion injury. Om data suggest that increased TNF-alpha and reduced IL-6 mRNA expression might be responsible. However, more studies are needed to decipher the exact mechanism.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 03:20:11