Open this publication in new window or tab >>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
2023-09-122023-09-122023-11-24Bibliographically approved