Inhibition of COX-2 signaling favors E. coli during urinary tract infection.
Soumitra Mohanty, Ciska Lindelauf, John Kerr White, Andrea Scheffschick, Ewa Ehrenborg, Isak Demirel, Hanna Brauner, Annelie Brauner
Author Information
Soumitra Mohanty: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Ciska Lindelauf: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
John Kerr White: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Andrea Scheffschick: Department of Medicine, Solna, Stockholm, Sweden.
Ewa Ehrenborg: Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine at BioClinicum, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Isak Demirel: iRiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
Hanna Brauner: Department of Medicine, Solna, Stockholm, Sweden.
Annelie Brauner: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. Annelie.Brauner@ki.se.
BACKGROUND: To avoid the overuse of antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), acting via cyclooxygenase (COX) inhibition, have been used to reduce pain and as an alternative treatment for uncomplicated urinary tract infections (UTIs). However, clinical studies evaluating NSAIDs versus antibiotics have reported an increased risk of acute pyelonephritis. Therefore, we hypothesized that COX inhibition could compromise the innate immune response and contribute to complications in patients with uncomplicated UTI. RESULTS: We here demonstrate that in particular COX-2 inhibition led to decreased expression of the antimicrobial peptides psoriasin and human β-defensin-2 in human uroepithelial cells. Psoriasin expression was altered in neutrophils and macrophages. COX-2 inhibition also had impact on the inflammasome mediated IL-1β expression in response to uroepithelial E. coli infection. Further, COX-2 inhibition downregulated free radicals and the epithelial barrier protein claudin 1, favoring infectivity. In addition, conditioned media from COX-2 inhibited uroepithelial cells infected with E. coli failed to activate macrophages. CONCLUSIONS: Taken together, our data suggests an adverse innate immune effect of COX-2 inhibition on uroepithelial cells during UTI.
