Abstract:Objective To study the expression of Fractalkine (FKN) in the kidney tissue of rats with renal fibrosis and the effect of IL-18BP on FKN. Methods Male Wister rats were randomly assigned to sham-operation (n=24), unilatral ureteral obstruction (UUO, n=22), and IL-18 binding protein (IL-18BP) treatment groups (n=23). The UUO model was prepared by unilateral ureteral ligation in the later two groups. The IL-18BP treatment group received an intraperitoneal injection of IL-18BP (0.1 mg/kg) every other day after UUO inducement, for 7 times, while normal saline was administered in the other two groups. Seven or eight rats of every group were sacrificed at 3, 7 or 14 days after IL-18BP or normal saline injections. FKN levels at various times were detected by immunohistochemistry and Western blot. Results Compared with the sham-operation group, FKN levels in the kidney tissue of the untreated UUO group increased significantly at all time points (P<0.01). IL-18BP treatment decreased significantly FKN levels in the kidney tissue at all time points compared with the untreated UUO group (P<0.01). Conclusions IL-18BP treatment may down-regulate the increased FKN levels of the rat kidney tissue caused by UUO, possibly thus delays the occurrence and development of renal fibrosis.
WANG Li-Min,LI Chun-Yu,ZHANG Jia-Bin et al. Effect of IL-18BP on Fractalkine chemokine expression in the kidney tissue of rats with renal fibrosis[J]. CJCP, 2013, 15(12): 1134-1138.
Koziolek MJ, Muller GA, Zapf A, Patschan D, Schmid H, Cohen CD, et al. Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure[J]. Nephrol Dial Transplant, 2010, 25(3): 684-698.
[2]
Klahr S, Morrissey J. Obstructive nephropathy and renal fibrosis[J]. Am J Physiol Renal Physiol, 2002, 283(5): F861-F875.
[3]
Yang XP, Mattagajasingh S, Su S, Chen G, Cai Z, Fox-Talbot K, et al. Fractalkine upregulates intercellular adhesion molecule-1 in endothelial cells through CX3CR1 and the Jak Stat5 pathway[J]. Circ Res, 2007, 9(10): 1001-1008.
[4]
Saederup N, Chan L, Lira SA, Charo IF. Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2-/-mice: evidence for independent chemokine functions in atherogenesis[J]. Circulation, 2008, 117(13): 1642-1648.
Wang J, Long Q, Zhang W, Chen N. Protective effects of exogenous interleukin 18-binding protein in a rat model of acute renal ischemia-reperfusion injury[J]. Shock, 2012, 37(3): 333-340.
[9]
Bani-Hani AH, Leslie JA, Asanuma H, Dinarello CA, Campbell MT, Meldrum DR, et al. IL-18 neutralization ameliorates obstruction-induced epithelial-mesenchymal transition and renal fibrosis[J]. Kidney Int, 2009, 76(5): 500-511.
Wyburn KR, Chadban SJ, Kwan T. Interleukin-18 binding protein therapy is protective in adriamycin nephropathy[J]. Am J Physiol Renal Physiol, 2013, 304(1): F68-F76.