Inhibition of kidney ischemia-reperfusion injury through local infusion of a TLR2 blocker

Hye J Kim; Sang J Park; Sumi Koo; Hee J Cha; Jong S Lee; Byungsuk Kwon; Hong R Cho

doi:10.1016/j.jim.2014.03.014

Inhibition of kidney ischemia-reperfusion injury through local infusion of a TLR2 blocker

J Immunol Methods. 2014 May:407:146-50. doi: 10.1016/j.jim.2014.03.014. Epub 2014 Mar 26.

Authors

Hye J Kim¹, Sang J Park², Sumi Koo¹, Hee J Cha³, Jong S Lee⁴, Byungsuk Kwon⁵, Hong R Cho⁶

Affiliations

¹ Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea.
² 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.
³ Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Republic of Korea; Department of Pathology, Ulsan University Hospital, University of Ulsan, Republic of Korea.
⁴ 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.
⁵ 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.
⁶ 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.

PMID: 24681240
DOI: 10.1016/j.jim.2014.03.014

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.

Keywords: Kidney ischemia–reperfusion injury; Toll-like receptor 2 blocker; Tubular epithelial cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Blocking / administration & dosage*
Antibodies, Blocking / adverse effects
Cell Movement / drug effects
Female
Humans
Infusions, Intravenous
Kidney / blood supply*
Killer Cells, Natural / drug effects*
Killer Cells, Natural / immunology
Mice
Mice, Inbred C57BL
Models, Animal
Reperfusion Injury / immunology*
Reperfusion Injury / therapy*
Toll-Like Receptor 2 / antagonists & inhibitors*

Substances

Antibodies, Blocking
Tlr2 protein, mouse
Toll-Like Receptor 2