Comparison of cyclosporine versus mycophenolate mofetil on expression of Fractalkine and CX3CR1 in chronic allograft nephropathy

Transplant Proc. 2006 Sep;38(7):2234-6. doi: 10.1016/j.transproceed.2006.06.046.

Abstract

Introduction: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Chemokine CX3CL1
  • Chemokines, CX3C / genetics*
  • Cyclosporine / pharmacology*
  • DNA Primers
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology*
  • Membrane Proteins / genetics*
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, CXCR3
  • Receptors, Chemokine / genetics*
  • Transplantation, Homologous

Substances

  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Cx3cl1 protein, rat
  • Cxcr3 protein, rat
  • DNA Primers
  • Membrane Proteins
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Cyclosporine
  • Mycophenolic Acid