@article{9b3183cd15d5498cbf78fe069297062f,
title = "Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis",
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.",
keywords = "COX-2, Chronic infection, Immunomodulatory therapy, Immunopathology, Mucosal immunology, Recurrent infection, UPEC, Urinary tract infection UTI, Uropathogenic E. coli",
author = "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 Hiroyuki Miyoshi and Matthias Mack and Schwendener, {Reto A.} and Hooton, {Thomas M.} and Stappenbeck, {Thaddeus S.} and Hansson, {Gunnar C.} and Stenson, {William F.} and Marco Colonna and Stapleton, {Ann E.} and Hultgren, {Scott J.}",
note = "Funding Information: We thank Joel Schilling and Karen Dodson for helpful discussions and for critical evaluation of this manuscript. Research reported in this publication was supported by the National Institutes of Health under award numbers U01AI095542 (M.C. & S.J.H.), U01AI095473 (G.C.H.), R01DK051406 (S.J.H.), R01DK071619 (T.S.S.), K08AI083746 (T.J.H.), and F30DK096751 (D.J.S.), the Office of Research, Women's Health SCOR Grant P50DK64540 (S.J.H., T.M.H. & A.E.S.), and a Mucosal Immunology Studies Team Consortium U01AI095776 pilot grant (T.J.H. and G.C.H.) and Young Investigator Award (T.J.H.); and by the German Research Foundation (M.M.), the Swedish Research Council 7461 (G.C.H.) and the IngaBritt and Arne Lundberg Foundation (G.C.H.). These funding agencies played no role in the design or outcomes of this study and the authors were not paid by any company or agency to write this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2014 The Authors.",
year = "2014",
doi = "10.1016/j.ebiom.2014.10.011",
language = "English",
volume = "1",
pages = "46--57",
journal = "EBioMedicine",
issn = "2352-3964",
number = "1",
}