Hannan, Thomas J. and Roberts, Pacita L. and Riehl, Terrence E. and van der Post, Sjoerd and Binkley, Jana M. and Schwartz, Drew J. and Miyoshi, Hiroyuki and Mack, Matthias and Schwendener, Reto A. and Hooton, Thomas M. and Stappenbeck, Thaddeus S. and Hansson, Gunnar C. and Stenson, William F. and Colonna, Marco and Stapleton, Ann E. and Hultgren, Scott J. (2014) Inhibition of Cyclooxygenase-2 Prevents Chronic and Recurrent Cystitis. EBIOMEDICINE, 1 (1). pp. 46-57. ISSN 2352-3964,
Full text not available from this repository. (Request a copy)Abstract
The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeutic strategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatment of mice with dexamethasone during acute UTI improved outcome by reducing the development of chronic cystitis, which predisposes to recurrent infection. Here we discovered soluble biomarkers engaged inmyeloid cell development and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of young women with UTI. Translation of these findings revealed that temperance of the neutrophil response early during UTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition of cyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladder epithelial 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 and drugs targeting cyclooxygenase-2 could prevent recurrent UTI. (C) 2014 The Authors. Published by Elsevier B.V.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; Immunomodulatory therapy; Mucosal immunology; Immunopathology; Uropathogenic E.coli; UPEC; COX-2; Urinary tract infection; UTI, recurrent infection; Chronic infection |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Aug 2019 11:54 |
| Last Modified: | 08 Aug 2019 11:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9323 |
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