Cyclosporine-induced renal injury induces toll-like receptor and maturation of dendritic cells.
BACKGROUND
The toll-like receptor (TLR) is stimulated by not only pathogen-associated molecular patterns but also endogenous TLR ligands provided by injured cells. The influence of cyclosporine A (CsA)-induced renal injury on TLR expression and subsequent signaling pathway was evaluated.


METHODS
Induction of chronic CsA nephropathy was made by administering CsA (15 mg/kg/day) for 28 days in rats. The TLR2 and TLR4 mRNA and protein expression, TLR-signaling pathway (MYD88, NF-kappaB and AP-1), putative TLR ligand (heat shock protein 70 [HSP70]), and maturation of dendritic cells were evaluated in CsA-treated rat kidneys.


RESULTS
Long-term CsA treatment upregulated TLR2 and TLR4 mRNA and protein expression on renal tubular cells, and these were accompanied by increased MYD88, NF-kappaB and AP-1 expression. Putative TLR ligand (HSP70) was also significantly increased in CsA-treated rat kidney compared with vehicle-treated rat kidney. CsA-treatment increased expression of TNF-alpha mRNA, the number of dendritic cells, and expression of MHC class II antigen. Double-labeling of markers of dendritic cells and MHC class II antigen revealed that matured dendritic cells increased in CsA-treated rat kidney.


CONCLUSIONS
CsA-induced renal injury stimulates components of innate immunity, and this finding suggests close association between CsA-induced renal injury and activation of innate immunity.
Lim
Sun Woo
SW
Cell Death Research Center, Department of Internal Medicine, The Catholic University of Korea, Seoul.
Li
Can
C
Ahn
Kyung Ohk
KO
Kim
Jin
J
Moon
In Sung
IS
Ahn
Curie
C
Lee
Jeong Ryul
JR
Yang
Chul Woo
CW
D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine / Q000633:toxicity*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000276:immunology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016572:Cyclosporine