title: Inhibition of kidney ischemia-reperfusion injury through local infusion of a TLR2 blocker.
abstract: Kidney ischemia-reperfusion injury (IRI) occurs as a result of complex interactions of kidney parenchymal cells and immune cells that are initiated by hypoxic damage of parenchymal cells. In particular, tubular epithelial cells (TECs) not only are susceptible to ischemia but also have an auto-loop system to amplify renal inflammation caused by ischemia and reperfusion. Since endogenous TLR2 ligands released from TECs trigger renal inflammation leading to kidney IRI in an autocrine manner, we hypothesized that local infusion of TLR2 blockers would prevent kidney IRI. In this study, we demonstrated that injection of antagonist anti-TLR2 mAb through the renal vein after cross-clamping significantly reduced the recruitment of NK cells to the kidney after IRI, a phenomenon that is governed by TLR2 signaling in TECs. In addition, intrarenal blocking of TLR2 signaling was shown to inhibit NK cell-mediated neutrophil infiltration and subsequent renal damage. Overall, our simple experiment system will be of help in testing the efficacy of candidate blockers targeting kidney parenchymal cells in inhibition of kidney IRI.
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea.
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea; Department of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Republic of Korea.
authors.forename: Sang J
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea.
authors.forename: Sumi
authors.initials: S
authors.lastname: Koo
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea; Department of Pathology, Ulsan University Hospital, University of Ulsan, Republic of Korea.
authors.forename: Hee J
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea; Department of Internal Medicine, Ulsan University Hospital and School of Medicine, University of Ulsan, Republic of Korea.
authors.forename: Jong S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea; School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea. Electronic address: bkwon@ulsan.ac.kr.
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea; Department of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Republic of Korea. Electronic address: hrcho@uuh.ulsan.kr.
authors.forename: Hong R
authors.initials: HR
authors.lastname: Cho
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage* / Q000009:adverse effects; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D015427:Reperfusion Injury / Q000276:immunology* / Q000628:therapy*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors*
chemical_list: D019138:Antibodies, Blocking; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
keywords: Kidney ischemia–reperfusion injury; Toll-like receptor 2 blocker; Tubular epithelial cell