Cargando…
The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells
The NLRP3 inflammasome, estrogen and antimicrobial peptides have all been found to have a vital role in the protection of the bladder urothelium. However, the interdependence between these protective factors during a bladder infection is currently unknown. Our aim was to investigate the role of NLRP...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526908/ https://www.ncbi.nlm.nih.gov/pubmed/37759520 http://dx.doi.org/10.3390/cells12182298 |
_version_ | 1785111093964701696 |
---|---|
author | Lindblad, Anna Wu, Rongrong Persson, Katarina Demirel, Isak |
author_facet | Lindblad, Anna Wu, Rongrong Persson, Katarina Demirel, Isak |
author_sort | Lindblad, Anna |
collection | PubMed |
description | The NLRP3 inflammasome, estrogen and antimicrobial peptides have all been found to have a vital role in the protection of the bladder urothelium. However, the interdependence between these protective factors during a bladder infection is currently unknown. Our aim was to investigate the role of NLRP3 in the regulation of antimicrobial peptides and estrogen signaling in bladder epithelial cells during a UPEC infection. Human bladder epithelial cells and CRISPR/Cas9-generated NLRP3-deficient cells were stimulated with the UPEC strain CFT073 and estradiol. The gene and protein expression were evaluated with microarray, qRT-PCR, western blot and ELISA. Microarray results showed that the expression of most antimicrobial peptides was reduced in CFT073-infected NLRP3-deficient cells compared to Cas9 control cells. Conditioned medium from NLRP3-deficient cells also lost the ability to suppress CFT073 growth. Moreover, NLRP3-deficient cells had lower basal release of Beta-defensin-1, Beta-defensin-2 and RNase7. The ability of estradiol to induce an increased expression of antimicrobial peptides was also abrogated in NLRP3-deficient cells. The decreased antimicrobial peptide expression might be linked to the observed reduced expression and activity of estradiol receptor beta in NLRP3-deficient cells. This study suggests that NLRP3 may regulate the release and expression of antimicrobial peptides and affect estrogen signaling in bladder epithelial cells. |
format | Online Article Text |
id | pubmed-10526908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105269082023-09-28 The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells Lindblad, Anna Wu, Rongrong Persson, Katarina Demirel, Isak Cells Article The NLRP3 inflammasome, estrogen and antimicrobial peptides have all been found to have a vital role in the protection of the bladder urothelium. However, the interdependence between these protective factors during a bladder infection is currently unknown. Our aim was to investigate the role of NLRP3 in the regulation of antimicrobial peptides and estrogen signaling in bladder epithelial cells during a UPEC infection. Human bladder epithelial cells and CRISPR/Cas9-generated NLRP3-deficient cells were stimulated with the UPEC strain CFT073 and estradiol. The gene and protein expression were evaluated with microarray, qRT-PCR, western blot and ELISA. Microarray results showed that the expression of most antimicrobial peptides was reduced in CFT073-infected NLRP3-deficient cells compared to Cas9 control cells. Conditioned medium from NLRP3-deficient cells also lost the ability to suppress CFT073 growth. Moreover, NLRP3-deficient cells had lower basal release of Beta-defensin-1, Beta-defensin-2 and RNase7. The ability of estradiol to induce an increased expression of antimicrobial peptides was also abrogated in NLRP3-deficient cells. The decreased antimicrobial peptide expression might be linked to the observed reduced expression and activity of estradiol receptor beta in NLRP3-deficient cells. This study suggests that NLRP3 may regulate the release and expression of antimicrobial peptides and affect estrogen signaling in bladder epithelial cells. MDPI 2023-09-18 /pmc/articles/PMC10526908/ /pubmed/37759520 http://dx.doi.org/10.3390/cells12182298 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lindblad, Anna Wu, Rongrong Persson, Katarina Demirel, Isak The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells |
title | The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells |
title_full | The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells |
title_fullStr | The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells |
title_full_unstemmed | The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells |
title_short | The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells |
title_sort | role of nlrp3 in regulation of antimicrobial peptides and estrogen signaling in upec-infected bladder epithelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526908/ https://www.ncbi.nlm.nih.gov/pubmed/37759520 http://dx.doi.org/10.3390/cells12182298 |
work_keys_str_mv | AT lindbladanna theroleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells AT wurongrong theroleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells AT perssonkatarina theroleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells AT demirelisak theroleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells AT lindbladanna roleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells AT wurongrong roleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells AT perssonkatarina roleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells AT demirelisak roleofnlrp3inregulationofantimicrobialpeptidesandestrogensignalinginupecinfectedbladderepithelialcells |