title: Exogenous augmenter of liver regeneration (ALR) attenuates inflammatory response in renal hypoxia re-oxygenation injury.
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.
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University , Chongqing , China and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Guo-Tao
authors.initials: GT
authors.lastname: Chen
authors.forename: Hang
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply*; D008297:Male; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; C495345:TLR4 protein, human; C088825:GFER protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors