Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure

Methods. Functional data were analysed in folic acid nephropathy (FAN) at different time points (up to day 142 after induction). Immunostaining for CX3C-L, CD3, S100A4, collagen type I, fibronectin, alpha-smooth muscle actin, Tamm-horsfall protein, aquaporin 1 and 2 as well as quantitative real-time PCR (qRT-PCR) for CX3C-L, CX3C-R and fibroblast-specific protein 1 (FSP-1) were performed. Additionally, regulatory mechanisms and functional activity of CX3C-L in murine proximal and distal tubular epithelial cells as well as in fibroblasts were investigated. Results. CX3C-L/GAPDH ratio was upregulated in FAN 3.4-fold at day 7 further increasing up to 7.1-fold at day 106. The expression of mRNA CX3C-L correlated well with CX3C-R (R-2 = 0.96), the number of infiltrating CD3+ cells (R-2 = 0.60) and the degree of tubulointerstitial fibrosis (R-2 = 0.56) and moderately with FSP-1 (R-2 = 0.33). Interleukin-1 beta, tumour necrosis factor-alpha, transforming growth factor-beta as well as the reactive oxygen species (ROS) H2O2 were identified by qRT-PCR as inductors of CX3C-L/fractalkine (FKN) in tubular epithelial cells. Functionally, CX3C-L/FKN chemoattracts peripheral blood mononuclear cells, activates several aspects of fibrogenesis and induces the mitogen-activated protein kinases in renal fibroblasts. Conclusions. In FAN, there is a good correlation between the expression of CX3C-L with markers of interstitial inflammation and fibrosis which may result from upregulation by pro-inflammatory and pro-fibrotic cytokines as well as by ROS in tubular epithelial cells. The FKN system may promote renal inflammation and renal fibrogenesis.