Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis

Thomas J. Hannan, Pacita L. Roberts, Terrence E. Riehl, Sjoerd van der Post, Jana M. Binkley, Drew J. Schwartz, Hiroyuki Miyoshi, Matthias Mack, Reto A. Schwendener, Thomas M. Hooton, Thaddeus S. Stappenbeck, Gunnar C. Hansson, William F. Stenson, Marco Colonna, Ann E. Stapleton, Scott J. Hultgren

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)46-57
Number of pages12
JournalEBioMedicine
Volume1
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Chronic infection
  • COX-2
  • Immunomodulatory therapy
  • Immunopathology
  • Mucosal immunology
  • Recurrent infection
  • UPEC
  • Urinary tract infection UTI
  • Uropathogenic E. coli

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Fingerprint Dive into the research topics of 'Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis'. Together they form a unique fingerprint.

  • Cite this

    Hannan, T. J., Roberts, P. L., Riehl, T. E., van der Post, S., Binkley, J. M., Schwartz, D. J., Miyoshi, H., Mack, M., Schwendener, R. A., Hooton, T. M., Stappenbeck, T. S., Hansson, G. C., Stenson, W. F., Colonna, M., Stapleton, A. E., & Hultgren, S. J. (2014). Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis. EBioMedicine, 1(1), 46-57. https://doi.org/10.1016/j.ebiom.2014.10.011