Influence of angiotensin II on expression of toll-like receptor 2 and maturation of dendritic cells in chronic cyclosporine nephropathy.
BACKGROUND
Angiotensin (Ang) II plays an important role in immune regulation. We evaluate the influence of the renin-angiotensin system (RAS) in the innate immune response caused by cyclosporine A (CsA)-induced renal injury.


METHODS
Two separate studies were performed in Sprague Dawley rats. First, losartan (LSRT, 10 mg/kg per day) was concurrently administered with CsA (15 mg/kg per day) for 28 days. Second, AngII (435 ng/kg/min) was infused with or without LSRT for 14 days.


RESULTS
AngII blockade with LSRT decreased toll-like receptor (TLR) 2 mRNA and protein expression, expression of tumor necrosis factor (TNF)-alpha mRNA, and expression of major histocompatibility complex class II antigen, which was upregulated in CsA-induced renal injury. The increased number of matured dendritic cells (DCs) in CsA-induced renal injury was also decreased by concomitant treatment of LSRT. Direct infusion of AngII increased TNF-alpha mRNA, TLR2 mRNA, and protein and the number of DCs, compared with the control rat kidney. In contrast, concomitant treatment of LSRT decreased all parameters.


CONCLUSIONS
AngII plays a pivotal role in activating the innate immune response in CsA-induced renal injury.
Ahn
Kyung Ohk
KO
Xenotransplantation Research Center, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Lim
Sun Woo
SW
Li
Can
C
Yang
Hyun Joo
HJ
Ghee
Jung Yeon
JY
Kim
Jin Young
JY
Kim
Su Hyun
SH
Kim
Jin
J
Yang
Chul Woo
CW
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate; D007668:Kidney / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D016572:Cyclosporine