TY  - JOUR
A1  - Paulus, Patrick
A1  - Rupprecht, Katrin
A1  - Baer, Patrick C.
A1  - Obermüller, Nicholas
A1  - Penzkofer, Daniela
A1  - Reissig, Christin
A1  - Scheller, Bertram
A1  - Holfeld, Johannes
A1  - Zacharowski, Kai
A1  - Dimmeler, Stefanie
A1  - Schlammes, Joelle
A1  - Urbschat, Anja
T1  - The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion
T2  - PLoS One
N2  - 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.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/33616
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-336165
SN  - 1932-6203
N1  - Copyright: © 2014 Paulus et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 9
IS  - (4):e94366
PB  - PLoS
CY  - Lawrence, Kan.
ER  -