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Am J Physiol Regul Integr Comp Physiol 293: R677-R685, 2007. First published May 30, 2007; doi:10.1152/ajpregu.00305.2007
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INFLAMMATION AND CYTOKINES

Expression of cyclooxygenase-2 in urinary bladder in rats with cyclophosphamide-induced cystitis

Mary Beth Klinger, Abbey Dattilio, and Margaret A. Vizzard

University of Vermont College of Medicine, Department of Neurology and Anatomy, Neurobiology, Burlington, Vermont

Submitted 30 April 2007 ; accepted in final form 28 May 2007

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 ≤ 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 ≤ 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.

urothelium; inflammatory infiltrates; detrusor; nerves



Address for reprint requests and other correspondence: M. A. Vizzard, Univ. of Vermont College of Medicine, Dept. of Neurology, D415A Given Research Bldg., Burlington, VT 05405 (e-mail: margaret.vizzard{at}uvm.edu)




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Am. J. Physiol. Renal Physiol.Home page
B. P. Cheppudira, B. M. Girard, S. E. Malley, K. C. Schutz, V. May, and M. A. Vizzard
Upregulation of vascular endothelial growth factor isoform VEGF-164 and receptors (VEGFR-2, Npn-1, and Npn-2) in rats with cyclophosphamide-induced cystitis
Am J Physiol Renal Physiol, September 1, 2008; 295(3): F826 - F836.
[Abstract] [Full Text] [PDF]




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