The role of caspase-1, caspase-4, NLRP3 and IL-1RA in bladder epithelial cells infected by uropathogenic Escherichia coli

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

Nyckelord

Urinary tract infection

inflammasome

uropathogenic Escherichia coli

NLRP3

caspase-1

caspase-4

IL-1RA

antimicrobial peptides

estrogen

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