Xenotransplantation Research Center, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
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. CONCLUSION: AngII plays a pivotal role in activating the innate immune response in CsA-induced renal injury.