Impact of Toll-like receptor 2 expression in renal allograft rejection.
BACKGROUND
An important role of TLR2 has been shown in various experimental models of renal ischaemia/reperfusion injury. To study the expression of TLR2 in renal allograft rejection systematically, we established an experimental rat transplantation model.


METHODS
TLR2 expression was analysed in 99 human renal allograft biopsies, and in rat allografts at Day 6 and 28 after experimental renal transplantation. To discriminate whether regulation of TLR2 was following immunological processes after allogeneic transplantation or was a consequence from ischaemia/reperfusion injury, control animals subjected to syngeneic transplantation or to ischaemia/reperfusion damage were also investigated.


RESULTS
TLR2 mRNA was significantly elevated in rat allografts with acute rejection on Day 6 and decreased spontaneously towards Day 28. TLR2 induction correlated with renal function and TLR2 excretion in the urine of transplanted rats. TLR2 staining was also significantly increased in human allografts with acute rejection. TLR2 protein could be localized in tubular epithelial cells and vascular endothelial cells, and in CD68- and CD4-positive infiltrating cells.


CONCLUSIONS
TLR2 is markedly up-regulated in both experimental and human acute renal allograft rejection. Our data suggest a role for TLR2 during allogen-dependent graft damage after renal transplantation.
Hoffmann
Ute
U
Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany. ute.hoffmann@klinik.uni-regensburg.de
Bergler
Tobias
T
Rihm
Munhie
M
Pace
Claudia
C
Krüger
Bernd
B
Jung
Bettina
B
Reinhold
Stephan W
SW
Farkas
Stefan
S
Rümmele
Petra
P
Krämer
Bernhard K
BK
Banas
Bernhard
B
D000818:Animals; D015153:Blotting, Western; D005260:Female; D005455:Fluorescent Antibody Technique; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D015854:Up-Regulation
D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2