title: Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic ischemia/reperfusion-injured rats via suppression of the TLR2/NF-κB pathway.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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-1β (IL-1β), 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-1β, 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.
authors.affiliation: Department of Gastroenterology, Central Hospital of Xianning City, Hubei Province, China.
authors.forename: Q-S
authors.initials: QS
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Central Hospital of Xianning City, Hubei Province, China.
authors.forename: Z-W
authors.initials: ZW
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Central Hospital of Xianning City, Hubei Province, China.
authors.forename: J-G
authors.initials: JG
authors.lastname: Xiong
authors.affiliation: Department of Gastroenterology, Central Hospital of Xianning City, Hubei Province, China.
authors.forename: S
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Central Hospital of Xianning City, Hubei Province, China.
authors.forename: X-F
authors.initials: XF
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Central Hospital of Xianning City, Hubei Province, China. Electronic address: 1042157787@qq.com.
authors.forename: X-C
authors.initials: XC
authors.lastname: Li
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000627:therapeutic use*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods; D008099:Liver / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017467:Receptors, Erythropoietin / Q000378:metabolism; D015427:Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; C000606206:Nfkbia protein, rat; D010446:Peptide Fragments; D017467:Receptors, Erythropoietin; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C117514:erythropoietin receptor (1-225); C000599851:erythropoietin, rat; D004921:Erythropoietin; D000072000:NF-KappaB Inhibitor alpha