The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion.
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 cr...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3988056?pdf=render |
| _version_ | 1819107883300683776 |
|---|---|
| author | Patrick Paulus Katrin Rupprecht Patrick Baer Nicholas Obermüller Daniela Penzkofer Christin Reissig Bertram Scheller Johannes Holfeld Kai Zacharowski Stefanie Dimmeler Joelle Schlammes Anja Urbschat |
| author_facet | Patrick Paulus Katrin Rupprecht Patrick Baer Nicholas Obermüller Daniela Penzkofer Christin Reissig Bertram Scheller Johannes Holfeld Kai Zacharowski Stefanie Dimmeler Joelle Schlammes Anja Urbschat |
| author_sort | Patrick Paulus |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T03:01:07Z |
| format | Article |
| id | doaj.art-a64b766c332d4f09a8e40d45a458e1e6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T03:01:07Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a64b766c332d4f09a8e40d45a458e1e62022-12-21T18:41:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9436610.1371/journal.pone.0094366The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion.Patrick PaulusKatrin RupprechtPatrick BaerNicholas ObermüllerDaniela PenzkoferChristin ReissigBertram SchellerJohannes HolfeldKai ZacharowskiStefanie DimmelerJoelle SchlammesAnja UrbschatAcute 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.http://europepmc.org/articles/PMC3988056?pdf=render |
| spellingShingle | Patrick Paulus Katrin Rupprecht Patrick Baer Nicholas Obermüller Daniela Penzkofer Christin Reissig Bertram Scheller Johannes Holfeld Kai Zacharowski Stefanie Dimmeler Joelle Schlammes Anja Urbschat The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion. PLoS ONE |
| title | The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion. |
| title_full | The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion. |
| title_fullStr | The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion. |
| title_full_unstemmed | The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion. |
| title_short | The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion. |
| title_sort | early activation of toll like receptor tlr 3 initiates kidney injury after ischemia and reperfusion |
| url | http://europepmc.org/articles/PMC3988056?pdf=render |
| work_keys_str_mv | AT patrickpaulus theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT katrinrupprecht theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT patrickbaer theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT nicholasobermuller theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT danielapenzkofer theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT christinreissig theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT bertramscheller theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT johannesholfeld theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT kaizacharowski theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT stefaniedimmeler theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT joelleschlammes theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT anjaurbschat theearlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT patrickpaulus earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT katrinrupprecht earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT patrickbaer earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT nicholasobermuller earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT danielapenzkofer earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT christinreissig earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT bertramscheller earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT johannesholfeld earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT kaizacharowski earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT stefaniedimmeler earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT joelleschlammes earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion AT anjaurbschat earlyactivationoftolllikereceptortlr3initiateskidneyinjuryafterischemiaandreperfusion |