Down-Regulated Receptor Interacting Protein 140 Is Involved in Lipopolysaccharide-Preconditioning-Induced Inactivation of Kupffer Cells and Attenuation of Hepatic Ischemia Reperfusion Injury

PLoS One. 2016 Oct 10;11(10):e0164217. doi: 10.1371/journal.pone.0164217. eCollection 2016.

Abstract

Background: Lipopolysaccharide (LPS) preconditioning is known to attenuate hepatic ischemia/reperfusion injury (I/RI); however, the precise mechanism remains unclear. This study investigated the role of receptor-interacting protein 140 (RIP140) on the protective effect of LPS preconditioning in hepatic I/RI involving Kupffer cells (KCs).

Methods: Sprague-Dawley rats underwent 70% hepatic ischemia for 90 minutes. LPS (100 μg/kg) was injected intraperitoneally 24 hours before ischemia. Hepatic injury was observed using serum and liver samples. The LPS/NF-κB (nuclear factor-κB) pathway and hepatic RIP140 expression in isolated KCs were investigated.

Results: LPS preconditioning significantly inhibited hepatic RIP140 expression, NF-κB activation, and serum proinflammatory cytokine expression after I/RI, with an observation of remarkably reduced serum enzyme levels and histopathologic scores. Our experiments showed that protection effects could be effectively induced in KCs by LPS preconditioning, but couldn't when RIP140 was overexpressed in KCs. Conversely, even without LPS preconditioning, protective effects were found in KCs if RIP140 expression was suppressed with siRNA.

Conclusions: Down-regulated RIP140 is involved in LPS-induced inactivation of KCs and hepatic I/RI attenuation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Down-Regulation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Kupffer Cells / cytology
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism*
  • Lipopolysaccharides / toxicity*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Microscopy, Fluorescence
  • NF-kappa B / metabolism
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Interacting Protein 1
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Adaptor Proteins, Signal Transducing
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Nuclear Proteins
  • Nuclear Receptor Interacting Protein 1
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha

Grants and funding

This project was supported by the National Science Foundation of China (No. 81170442 and 81470899), the Important Scientific Research Project of the Ministry of Education (No. 211153), the National Scholarship Foundation (No. 201208505116), and the Outstanding Young Talent Fund of the Second Hospital of CQMU (2011).