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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.
This article was published in the following journal.
Inflammasomes are cytosolic, multimeric protein complexes, capable of activating pro-inflammatory cytokines such as IL-1β and IL-18, which play a key role in host defence. Inflammasome components are...
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We studied the production of PGE2 by human conjunctival and corneal cells in response to inflammation, and reduction of inflammation with non-steroidal anti-inflammatory drugs. Primary cultures of hum...
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HIV persists despite antiretroviral therapy (ART) and is associated with chronic inflammation. This inflammation is thought to prevent an effective immune response against the virus and is...
A heterogeneous, immature population of myeloid cells that can suppress the activity of T-CELLS and NATURAL KILLER CELLS in the INNATE IMMUNE RESPONSE and ADAPTIVE IMMUNE RESPONSE. They play important roles in ONCOGENESIS; INFLAMMATION; and INFECTION.
The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
A lipocalin of approximately 200 amino acids that functions as an iron transporter and is expressed by cells of BONE MARROW and many other cells with secretory functions. It is involved in APOPTOSIS and may function to limit pathogenic bacterial growth as part of the INNATE IMMUNE RESPONSE.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
A member of the INTERLEUKIN-1 protein family involved in the maturation of TH2 CELLS and the activation of MAST CELLS; BASOPHILS; EOSINOPHILS and NK CELLS. It is also produced by ENDOTHELIAL CELLS; EPITHELIAL CELLS and FIBROBLASTS; where it can function as an alarmin to modulate immune and inflammatory responses to tissue damage.
Non-invasive bladder cancer is a cancer that is only in the inner lining of the bladder. Invasive bladder cancer is cancer that has spread into the deeper walls of the bladder. When the cancer has spread outside the bladder to other parts of the body, th...