Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis

Abstract

Alterations in the expression of the chemokine, fractalkine (CX3CL1), were examined in the urinary bladder after cyclophosphamide (CYP)-induced cystitis of varying duration: acute (4 h or 48 h), or chronic (10 day). CYP-induced cystitis significantly ( p ≤ 0.01) increased fractalkine protein expression in the urinary bladder with acute (48 h) and chronic CYP treatment. Western blot analysis also demonstrated significantly ( p ≤ 0.01) increased fractalkine expression in the whole urinary bladder with acute (1.5–2.2-fold) and chronic (3-fold) CYP-induced cystitis. Immunohistochemistry for fractalkine-immunoreactivity revealed little fractalkine-IR in control or acute (4 h) CYP-treated rat urinary bladders except in a vascular bed but showed no colocalization with nerve fibers in the suburothelial plexus in any experimental group. However, expression was significantly ( p ≤ 0.001) upregulated in the urothelium with 48 h or chronic CYP treatment. Similarly, fractalkine receptor (CX3CR1)-IR was significantly ( p ≤ 0.001) upregulated in the urothelium with 48 h or chronic CYP treatment. These studies demonstrated upregulation of the chemokine, fractalkine, in the urinary bladder and specifically in the urothelium with CYP-induced cystitis. Chemokines, and specifically, fractalkine, may be another class of neuromodulatory agents upregulated in the urinary bladder that can affect micturition function and sensory processing with cystitis and may represent novel, drug targets for cystitis.