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Inhibition of COX-2 signaling favors E. coli during urinary tract infection
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
Department of Medicine, Solna, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Solna, Sweden.
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2023 (English)In: Journal of Inflammation, E-ISSN 1476-9255, Vol. 20, no 1, article id 30Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023. Vol. 20, no 1, article id 30
Keywords [en]
Antimicrobial peptide, COX-2, Cytokines, E. coli, Urinary tract infection
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:oru:diva-108228DOI: 10.1186/s12950-023-00356-9ISI: 001066487100001PubMedID: 37697284Scopus ID: 2-s2.0-85170402304OAI: oai:DiVA.org:oru-108228DiVA, id: diva2:1796268
Funder
Olle Engkvists stiftelseRegion StockholmSwedish Association of Persons with Neurological DisabilitiesThe Karolinska Institutet's Research FoundationSwedish Society for Medical Research (SSMF)Swedish Cancer SocietyThe Swedish Medical AssociationÅke Wiberg FoundationMagnus Bergvall FoundationKarolinska Institute
Note

This research was funded by the Stiftelsen Olle Engkvist Byggmästare, Region Stockholm (ALF project) and Swedish Neurological Association (AB). Karolinska Institutet’s Research Foundation (SM, HB, and AB). HB is supported by grants from the Swedish Society for Medical Research, the Swedish Cancer Foundation, the Swedish Medical Association, Region Stockholm (clinical research appointment), Hudfonden, Clas Groschinsky, Åke Wiberg, and Magnus Bergvall. Open access funding provided by Karolinska Institute.

Available from: 2023-09-12 Created: 2023-09-12 Last updated: 2023-10-20Bibliographically approved

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