To Örebro University

oru.seÖrebro University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
IL-1RA is part of the inflammasome-regulated immune response in bladder epithelial cells and influences colonization of uropathogenic E. coli
Örebro University, School of Medical Sciences. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))
Örebro University, School of Medical Sciences. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))ORCID iD: 0009-0006-2517-034X
Örebro University, School of Medical Sciences. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))
2019 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 123, article id 154772Article in journal (Refereed) Published
Abstract [en]

The NLRP3 inflammasome, IL-1β release and pyroptosis (cell lysis) have recently been proposed to be essential for the progression of urinary tract infection (UTI) and elimination of intracellular bacterial niches. However, the effects of IL-1R antagonist (IL-1RA) on immune responses during UTI, except for its ability to disrupt IL-1β signalling, are not well understood. The aim of this study was to investigate the role of IL-1RA in UPEC colonization of bladder epithelial cells and the subsequent host inflammatory response. Human bladder epithelial cells (5637) and CRISPR/Cas9 generated NLRP3 and caspase-1 knockdown cells and IL-1RA knockout cells were stimulated with the UPEC isolate CFT073. The results showed that the UPEC virulence factor α-hemolysin is essential for IL-1RA release, and that the inflammasome-associated proteins caspase-1 and NLRP3 affect the release of IL-1RA. IL-1RA deficient cells showed a reduced adherence and invasion by CFT073 compared to wild-type cells, suggesting that IL-1RA may oppose mechanisms that protects against bacterial colonization. A targeted protein analysis of inflammation-related proteins showed that the basal expression of 23 proteins and the UPEC-induced expression of 10 proteins were significantly altered in IL-1RA deficient bladder epithelial cells compared to Cas9 control cells. This suggests that IL-1RA has a broad effect on the inflammatory response in bladder epithelial cells.

Place, publisher, year, edition, pages
Academic Press, 2019. Vol. 123, article id 154772
Keywords [en]
IL-1 receptor antagonist, Inflammasome, NLRP3, Urinary tract infections, Uropathogenic Escherichia coli
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:oru:diva-75559DOI: 10.1016/j.cyto.2019.154772ISI: 000487576400023PubMedID: 31299415Scopus ID: 2-s2.0-85068516287OAI: oai:DiVA.org:oru-75559DiVA, id: diva2:1340772
Funder
Swedish Society for Medical Research (SSMF)
Note

Funding Agencies:

Research Committee of Örebro County Council  

Faculty of Medicine and Health at Örebro University  

Capio Research Foundation 

Available from: 2019-08-06 Created: 2019-08-06 Last updated: 2024-01-02Bibliographically approved
In thesis
1. The role of caspase-1, caspase-4, NLRP3 and IL-1RA in bladder epithelial cells infected by uropathogenic Escherichia coli
Open this publication in new window or tab >>The role of caspase-1, caspase-4, NLRP3 and IL-1RA in bladder epithelial cells infected by uropathogenic Escherichia coli
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Urinary tract infection is one of the most common infections and is mostlycaused by uropathogenic Escherichia coli (UPEC). The inflammasomeassociatedproteins caspase-1, caspase-4 and NLRP3 are essential in the hostcell response during urinary tract infection by regulating IL-1β release. Thepro-inflammatory effects of IL-1β can be inhibited by binding of the IL-1receptor antagonist (IL-1RA) to the IL-1 receptor. The aim of this thesis is toinvestigate what role caspase-1, caspase-4, NLRP3 and IL-1RA have on the proinflammatoryhost response evoked by UPEC and their role in recurrent UTI.

The results showed that the inflammasome-associated proteinscaspase-1, caspase-4 and NLRP3 are involved in cytokine and chemokinerelease and in antimicrobial activities of neutrophils during UTI. Weconclude that IL-1RA influences the release of various inflammatoryproteins during a UPEC infection from bladder epithelial cells. In addition,deficiency in IL-1RA led to decreased UPEC colonization and invasion ofbladder epithelial cells. Our results also show that NLRP3 has a regulativefunction on estrogen signalling and the expression of antimicrobialpeptides. Additionally, we found that capsase-1 and caspase-4 can regulatethe gene expression of important immune regulators, including TLR4,antimicrobial peptides, cytokines and chemokines.

Together, our results show that that the inflammasome-associatedproteins caspase-1, caspase-4, NLRP3 and IL-IRA are important immuneregulatorsduring UPEC infection in bladder epithelial cells. They regulateUPEC colonization, cytokines and chemokines release, antimicrobialactivities of neutrophils and estrogen signalling.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2023. p. 72
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 284
Keywords
Urinary tract infection, inflammasome, uropathogenic Escherichia coli, NLRP3, caspase-1, caspase-4, IL-1RA, antimicrobial peptides, estrogen
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-108232 (URN)9789175295268 (ISBN)9789175295275 (ISBN)
Public defence
2023-12-08, Örebro universitet, Campus USÖ, hörsal X1, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2023-09-12 Created: 2023-09-12 Last updated: 2023-11-24Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Lindblad, AnnaPersson, KatarinaDemirel, Isak

Search in DiVA

By author/editor
Lindblad, AnnaPersson, KatarinaDemirel, Isak
By organisation
School of Medical Sciences
In the same journal
Cytokine
Microbiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 373 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf