Abstract
BackgroundLipopolysaccharide (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).MethodsSprague—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.ResultsLPS 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.ConclusionsDown-regulated RIP140 is involved in LPS-induced inactivation of KCs and hepatic I/RI attenuation.
Highlights
Hepatic ischemic/reperfusion injury (I/RI) is a key reason for liver dysfunction and failure after hepatic trauma, resection, and liver transplantation [1, 2]
Our experiments showed that protection effects could be effectively induced in Kupffer cells (KCs) by LPS preconditioning, but couldn’t when receptor-interacting protein 140 (RIP140) was overexpressed in KCs
Even without LPS preconditioning, protective effects were found in KCs if RIP140 expression was suppressed with siRNA
Summary
Hepatic ischemic/reperfusion injury (I/RI) is a key reason for liver dysfunction and failure after hepatic trauma, resection, and liver transplantation [1, 2]. Endotoxin tolerance induction seems to be effective in alleviating the toxic effects of LPS and in protecting against noninfectious challenge such as I/RI. It has been reported that endotoxin tolerance can attenuate I/RI in various organs including liver [11,12,13], while the precise molecular mechanism remains unclear. In liver, it is known that endotoxin tolerance induction is closely correlated with LPS-related TLRs (Toll-like receptors)/NF-κB signal pathways of Kupffer cells (KCs) [14, 15]. Lipopolysaccharide (LPS) preconditioning is known to attenuate hepatic ischemia/reperfusion injury (I/RI); 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)
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