Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic ischemia/reperfusion-injured rats via suppression of the TLR2/NF-κB pathway.
Transplant Proc
; 47(2): 283-9, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25769561
ABSTRACT
INTRODUCTION:
The inflammatory response plays an important role in liver dysfunction after hepatic ischemia/reperfusion (I/R), which is tightly regulated by the Toll-like receptor 2 (TLR2)/nuclear factor (NF)-κB pathway; suppression of TLR2/NF-κB signaling has therefore become a promising target for anti-inflammatory treatment in hepatic I/R injury. Erythropoietin (EPO) is a glycoprotein cytokine produced primarily by the kidney that has anti-inflammatory activities. The purpose of the present study was to investigate the effect of EPO preconditioning, if any, against hepatic I/R injury in rats and its underlying mechanisms. MATERIALS ANDMETHODS:
Male Sprague-Dawley rats were subjected to partial (70%) hepatic ischemia for 45 minutes after pretreatment with either saline or EPO followed by 24-hour reperfusion. Hepatic injury was evaluated according to biochemical and histopathologic examinations. The expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were measured by using enzyme-linked immunosorbent assay and real-time polymerase chain reaction. The expression of nuclear translocation and phosphorylation of NF-κB p65, EPOR receptor (EPOR), p-EPOR, p-IκB-α, IκB-α, and TLR2 were determined by using Western blot analysis.RESULTS:
EPO treatment significantly improved hepatic function and histology, as indicated by reduced transaminase levels and pathologic changes. The expression of TNF-α, IL-1ß, IL-6, p-IκB-α, and TLR2 was significantly decreased with up-regulation of p-EPOR by EPO. Moreover, EPO pretreatment also reduced I/R-induced the phosphorylation and nuclear translocation of NF-κB p65 subunits in liver tissue, but EPO had no influence on the expression of p65 and IκB-α.CONCLUSIONS:
These results suggest that EPO pretreatment ameliorates hepatic I/R injury, which is involved in suppressing TLR2/NF-κB-mediated inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
/
Eritropoetina
/
Fator de Transcrição RelA
/
Fígado
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article