Inhibition of COX-2 signaling favors E. coli during urinary tract infection.
Antimicrobial peptide
COX-2
Cytokines
E. coli
Urinary tract infection
Journal
Journal of inflammation (London, England)
ISSN: 1476-9255
Titre abrégé: J Inflamm (Lond)
Pays: England
ID NLM: 101232234
Informations de publication
Date de publication:
11 Sep 2023
11 Sep 2023
Historique:
received:
22
12
2022
accepted:
21
08
2023
medline:
12
9
2023
pubmed:
12
9
2023
entrez:
11
9
2023
Statut:
epublish
Résumé
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. 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. Taken together, our data suggests an adverse innate immune effect of COX-2 inhibition on uroepithelial cells during UTI.
Sections du résumé
BACKGROUND
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
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
CONCLUSIONS
Taken together, our data suggests an adverse innate immune effect of COX-2 inhibition on uroepithelial cells during UTI.
Identifiants
pubmed: 37697284
doi: 10.1186/s12950-023-00356-9
pii: 10.1186/s12950-023-00356-9
pmc: PMC10496388
doi:
Types de publication
Journal Article
Langues
eng
Pagination
30Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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