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Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis

Journal article
Authors T. J. Hannan
P. L. Roberts
T. E. Riehl
Sjoerd van der Post
J. M. Binkley
D. J. Schwartz
H. Miyoshi
M. Mack
R. A. Schwendener
T. M. Hooton
T. S. Stappenbeck
Gunnar C. Hansson
W. F. Stenson
M. Colonna
A. E. Stapleton
S. J. Hultgren
Published in EBioMedicine
Volume 1
Issue 1
Pages 46-57
ISSN 2352-3964
Publisher Elsevier
Publication year 2014
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 46-57
Language en
Keywords Chronic infection, COX-2, Immunomodulatory therapy, Immunopathology, Mucosal immunology, Recurrent infection, UPEC, Urinary tract infection UTI, Uropathogenic E. coli
Subject categories Clinical Medicine


The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.

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