Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis.
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<or=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<or=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<or=0.001) upregulated in the urothelium with 48 h or chronic CYP treatment. Similarly, fractalkine receptor (CX3CR1)-IR was significantly (p<or=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.
Yuridullah
Ruhin
R
University of Vermont College of Medicine, Department of Neurology, Burlington, VT 05405, USA.
Corrow
Kimberly A
KA
Malley
Susan E
SE
Vizzard
Margaret A
MA
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism*; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018121:Receptors, Cytokine / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D003520:Cyclophosphamide; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase