title: The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion.
abstract: Acute kidney injury (AKI) is one of the most important complications in hospitalized patients and its pathomechanisms are not completely elucidated. We hypothesize that signaling via toll-like receptor (TLR)-3, a receptor that is activated upon binding of double-stranded nucleotides, might play a crucial role in the pathogenesis of AKI following ischemia and reperfusion (IR). Male adult C57Bl6 wild-type (wt) mice and TLR-3 knock-out (-/-) mice were subjected to 30 minutes bilateral selective clamping of the renal artery followed by reperfusion for 30 min 2.5h and 23.5 hours or subjected to sham procedures. TLR-3 down-stream signaling was activated already within 3 h of ischemia and reperfusion in post-ischemic kidneys of wt mice lead to impaired blood perfusion followed by a strong pro-inflammatory response with significant neutrophil invasion. In contrast, this effect was absent in TLR-3-/- mice. Moreover, the quick TLR-3 activation resulted in kidney damage that was histomorphologically associated with significantly increased apoptosis and necrosis rates in renal tubules of wt mice. This finding was confirmed by increased kidney injury marker NGAL in wt mice and a better preserved renal perfusion after IR in TLR-3-/- mice than wt mice. Overall, the absence of TLR-3 is associated with lower cumulative kidney damage and maintained renal blood perfusion within the first 24 hours of reperfusion. Thus, we conclude that TLR-3 seems to participate in the pathogenesis of early acute kidney injury.
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Paulus
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Rupprecht
authors.affiliation: Department of Internal Medicine III, Division of Nephrology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Baer
authors.affiliation: Department of Internal Medicine III, Division of Nephrology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Obermüller
authors.affiliation: Institute of Cardiovascular Regeneration, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Penzkofer
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Reissig
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Scheller
authors.affiliation: Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Holfeld
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.affiliation: Institute of Cardiovascular Regeneration, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Joelle
authors.initials: J
authors.lastname: Schlammes
authors.affiliation: Faculty of Medicine, Philipps-University Marburg, Marburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Urbschat
mesh_terms: D000818:Animals; D007668:Kidney / Q000098:blood supply* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000098:blood supply / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3
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