2065 TOLL-LIKE RECEPTOR 3 (TLR3) PRETREATMENT PROTECTS IN RENAL ISCHEMIC INJURY

Abstract

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery I1 Apr 20102065 TOLL-LIKE RECEPTOR 3 (TLR3) PRETREATMENT PROTECTS IN RENAL ISCHEMIC INJURY Jason Hedges and Michael Conlin Jason HedgesJason Hedges Tigard, OR More articles by this author and Michael ConlinMichael Conlin Portland, OR More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2125AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ischemic preconditioning, a phenomenon induced by periods of brief ischemia followed by reperfusion, renders an organ more tolerant to future ischemia/reperfusion injury. Pretreatment with other agonists such as lipopolysaccharide (LPS) that activate pro-inflammatory and inflammatory mediators have been shown to protect in renal ischemic injury. Toll-like receptors mediate signal transduction pathways of the innate immune system that govern inflammatory cytokines. Using polyinosine-polycytidylic acid (Poly I:C), a ligand for Toll-like receptor 3 (TLR3), we determined the role of TLR3 preconditioning on renal function and histology in a murine renal ischemia model. METHODS A total of 24 C57BL/6J mice (Jackson Laboratories, Maine) were divided into 4 groups. Group 1 was vehicle control (normal saline); Group 2 was our positive control (LPS 16 mg/kg); Group 3 was Poly I:C (1.6 mg/kg, a synthetic analog of dsRNA and ligand for TLR3); and Group 4 was sham operation. Groups 1-3 underwent intraperitoneal injection 48 hours prior to the ischemic event. On day 0, mice were anesthetized and underwent bilateral renal pedicle clamping for 45 minutes. After unclamping, Doppler ultrasound was used to verify renal pedicle blood flow. Midline incisions were then closed and the mice were allowed to recover. Blood samples were taken on days 0 and 2 for serum creatinine analysis. Kidneys were harvested on day 2 for histological study. RESULTS All mice survived the 45 minutes of bilateral renal pedicle clamping. Group 1 (normal saline) had 4-fold greater increase (p<0.05) in serum creatinine levels after 2 days compared to Group 4 (sham operation). Group 2 (LPS) had significantly less creatinine rise than group 1. Group 3 (Poly I:C) serum creatinine levels after 2 days were the same as Group 4 (sham operation). On histological study, Group 1 (normal saline) had severe fibrosis and cellular damage, Group 2 (LPS) had minor inflammation, while Group 3 (Poly I:C) and Group 4 (sham operation) had normal histology. CONCLUSIONS Bilateral renal pedicle clamping for 45 minutes results in elevated serum creatinine levels and histological renal damage after 2 days. Pretreatment of the mice with LPS and Poly I:C (a ligand for TLR3) protected the mice from both a rise in serum creatinine levels and histological evidence of renal damage. These results taken together indicate that TLR3 may play an important novel role in protection of renal ischemic injury. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e803 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Hedges Tigard, OR More articles by this author Michael Conlin Portland, OR More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...