Comparison of cyclosporine versus mycophenolate mofetil on expression of Fractalkine and CX3CR1 in chronic allograft nephropathy.
BACKGROUND
We sought to investigate whether there was a difference between cyclosporine (CsA) and mycophenolate mofetil (MMF) to affect the expression of Fractalkine/CX3CR1 in chronic allograft nephropathy (CAN).


METHODS
The Sprague-Dawley Wistar rat accelerated kidney sclerosis model was performed as modified from the procedure of Kamada. Recipients were divided into three oral treatment groups (each group n = 8): group A was CsA 10 mg/kg . d for 10 days followed by vehicle; group B was CsA 10 mg/kg . d for 10 days followed by CsA 6 mg/kg.d; group C was CsA 10 mg/kg . d for 10 days followed by MMF 20 mg/kg . d. Pathological changes graded according to Banff 97 Standards were observed at 4, 8, and 12 weeks posttransplantation. The immunohistochemistry and quantitative real-time fluorescence polymerase chain reaction (PCR) were used to assess the distribution and expression of Fractalkine/CX3CR1 in the grafted kidney.


RESULTS
Fractalkine/CX3CR1 were mostly expressed in the tubulointerstitium and tubular epithelial cell basolateral membrane. A proportion of the vessel showed positive staining for Fractalkine/CX3CR1, occasionally in glomerular parietal wall cells. The expression of Fractalkine/CX3CR1 in grafted kidneys at all the time points was significantly less in the MMF than in the CsA group or the control group (P < .05). Real-time fluorescence quantitative PCR revealed similar outcomes as immunohistochemistry. The expression of Fractalkine coincided with CX3CR1.


CONCLUSIONS
Fractalkine/CX3CR1 may play an important role in the development of interstitial fibrosis in CAN. Different immunosuppressants have various effects on expression of the Fractalkine/CX3CR1.
Cao
G
G
Transplantation Institute, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, P.R. China.
Lu
Y
Y
Gao
R
R
Xin
Y
Y
Teng
D
D
Wang
J
J
Wang
L
L
Li
Y
Y
D000818:Animals; D001483:Base Sequence; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics*; D016572:Cyclosporine / Q000494:pharmacology*; D017931:DNA Primers; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics*; D014184:Transplantation, Homologous
D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; C515189:Cxcr3 protein, rat; D017931:DNA Primers; D008565:Membrane Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D016572:Cyclosporine; D009173:Mycophenolic Acid