Inhibition of Cyclooxygenase-2 Prevents Chronic and Recurrent Cystitis
| العنوان: | Inhibition of Cyclooxygenase-2 Prevents Chronic and Recurrent Cystitis |
|---|---|
| المؤلفون: | Thomas M. Hooton, Thomas J. Hannan, William F. Stenson, Reto A. Schwendener, Marco Colonna, Scott J. Hultgren, Sjoerd van der Post, Pacita L. Roberts, Ann E. Stapleton, Terrence E. Riehl, Matthias Mack, Jana Binkley, Hiroyuki Miyoshi, Gunnar C. Hansson, Thaddeus S. Stappenbeck, Drew J. Schwartz |
| المساهمون: | University of Zurich, Hultgren, Scott J |
| المصدر: | EBioMedicine EBioMedicine, Vol 1, Iss 1, Pp 46-57 (2014) |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Myeloid, lcsh:Medicine, urologic and male genital diseases, CD, clusters of differentiation, Immunopathology, Immunomodulatory therapy, NSAID, non-steroidal anti-inflammatory drug, Urinary tract infection (UTI), G-CSF or CSF3, granulocyte colony-stimulating factor, lcsh:R5-920, UPEC, uropathogenic E. coli, Urinary tract infection, MCP-1 or CCL2, monocyte chemotactic protein 1, 10061 Institute of Molecular Cancer Research, MAb, monoclonal antibody, General Medicine, Chronic Cystitis, female genital diseases and pregnancy complications, 3. Good health, Chronic infection, medicine.anatomical_structure, Mucosal immunology, Original Article, M-CSF or CSF1, macrophage colony-stimulating factor, lcsh:Medicine (General), medicine.drug, UTI, urinary tract infection, Urinary system, rUTI, recurrent urinary tract infection, GRO-α or CXCL1, growth-regulated alpha protein, Biology, General Biochemistry, Genetics and Molecular Biology, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, IL-8 or CXCL8, interleukin-8, ASB, asymptomatic bacteriuria, IBC, intracellular bacterial community, Dexamethasone, lcsh:R, COX-2, medicine.disease, bacterial infections and mycoses, Uropathogenic E. coli, COX, cyclooxygenase, Immunology, 570 Life sciences, biology, UPEC, UTI, recurrent infection |
| الوصف: | 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 in myeloid 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. Graphical abstract Highlights • Discovery of serum biomarkers of recurrent UTI (rUTI) in women implicates enhanced myeloid cell responses. • Inhibition of cyclooxygenase-2 disrupts bladder epithelial transmigration by neutrophils and protects against rUTI in mice. • Bladder epithelial remodeling that occurs consequent to chronic infection enhances mucosal sensitivity to neutrophil damage. |
| وصف الملف: | EBioMedicine 1-46-2014-Hannan.pdf - application/pdf; EBioMedicine 1-46-2014-Hannan-suppl.pdf - application/pdf |
| تدمد: | 2352-3964 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee789ffe31f98cdfe0d4c68286d780f3 https://pubmed.ncbi.nlm.nih.gov/26125048 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ee789ffe31f98cdfe0d4c68286d780f3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
|---|