Expression of cyclooxygenase-2 in urinary bladder in rats with cyclophosphamide-induced cystitis.
These studies examined the expression of cyclooxygenase-2 (COX-2) expression in the urothelium and suburothelial space and detrusor from rats treated with cyclophosphamide (CYP) to induce acute (4 h), intermediate (48 h), or chronic (10-day) cystitis. Western blot analysis and immunohistochemistry were used to demonstrate COX-2 expression. In whole mount preparations of urinary bladder, nerve fibers in the suburothelial plexus, and inflammatory cell infiltrates were characterized for COX-2 expression after CYP-induced cystitis. COX-2 expression significantly (P <or= 0.01) increased in the urothelium + suburothelium and detrusor smooth muscle with acute, intermediate, and chronic (10-day) CYP-induced cystitis, but expression in urothelium + suburothelium was significantly greater. CYP-induced upregulation of COX-2 showed by immunostaining in the urothelium + suburothelium was similar to that observed with Western blot analysis and also demonstrated COX-2 inflammatory cell infiltrates (CD86+) and nerve fibers (PGP+) in the suburothelial plexus. Although COX-2 expression was significantly (P <or= 0.01) increased in detrusor smooth muscle, immunohistochemistry failed to demonstrate an obvious change in COX-2-immunoreactivity (IR) in detrusor muscle, but COX-2 inflammatory infiltrates were present throughout the detrusor. COX-2-IR nerve fibers exhibited increased density in the suburothelial plexus with acute or chronic CYP-induced cystitis. COX-2-IR macrophages (CD86+) were present throughout the urinary bladder with acute and chronic CYP-induced cystitis. These studies demonstrate cellular targets in the urinary bladder where COX-2 inhibitors may act.
Klinger
Mary Beth
MB
Univ. of Vermont College of Medicine, Dept. of Neurology, D415A Given Research Bldg., Burlington, VT 05405. margaret.vizzard@uvm.edu).
Dattilio
Abbey
A
Vizzard
Margaret A
MA
D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D009130:Muscle, Smooth / Q000201:enzymology* / Q000276:immunology / Q000294:innervation; D009412:Nerve Fibers / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000201:enzymology* / Q000276:immunology / Q000294:innervation; D019459:Urothelium / Q000201:enzymology / Q000276:immunology
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat