1. Exogenous augmenter of liver regeneration (ALR) attenuates inflammatory response in renal hypoxia re-oxygenation injury.
- Author
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Li Y, Zhang L, Liu Q, Chen GT, and Sun H
- Subjects
- Animals, Cells, Cultured, Disease Models, Animal, Down-Regulation drug effects, Epithelial Cells, Immunity, Innate, Interleukin-1beta metabolism, Interleukin-6 metabolism, Male, NF-kappa B metabolism, Proteins metabolism, RNA, Messenger metabolism, Rats, Reperfusion Injury metabolism, Signal Transduction drug effects, Toll-Like Receptor 4 metabolism, Kidney blood supply, NF-kappa B immunology, Proteins pharmacology, Reperfusion Injury immunology, Toll-Like Receptor 4 immunology
- Abstract
Recent studies have highlighted the role of the innate immune system in initiating the inflammatory cascade which leads to detrimental changes in renal ischemia reperfusion (I/R) injury. The augmenter of liver regeneration (ALR) is an anti-apoptosis factor which is highly expressed in renal tubulars of renal cortex and medulla after inducing renal I/R injury in rats. It has been shown that exogenous ALR can enhance renal tubular regeneration. However, whether ALR's protective effect against renal I/R injury results from its immune regulatory function remains unknown. Using rat renal tubular epithelial cell (NRK-52E), we investigate the effect of recombinant rat ALR (rrALR) on immune inflammatory response in hypoxia re-oxygenation (H/R) injury in vitro, and further discuss the possible mechanisms. Cultured NRK-52E cells subjected to hypoxia for 6 h followed by re-oxygenation for 12, 24 and 72 h are administered with different doses of rrALR. Expression of Toll-like receptor 4 (TLR4) and transcription nuclear factor-κB (NF-κB) is assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) and western blot. Expression of interleukin (IL)-6 and IL-1β are determined by enzyme-linked immunosorbent assay (ELISA). In rrALR intervened H/R cells, TLR4 and NF-κB are down regulated at both mRNA and protein levels compare with those in control cells. Also, rrALR appears to downregulate IL-6 and IL-1β expression in concentration-dependent manners. In conclusion, rrALR protects NRK-52E cells from H/R injury possibly by relieving the inflammatory response through regulation of TLR4-NF-κB signaling pathway.
- Published
- 2014
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