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...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/18/2298 |
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| author | Anna Lindblad Rongrong Wu Katarina Persson Isak Demirel |
| author_facet | Anna Lindblad Rongrong Wu Katarina Persson Isak Demirel |
| author_sort | Anna Lindblad |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T22:56:06Z |
| format | Article |
| id | doaj.art-3c47c93b74414c5f99ec260f7a2dc732 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T22:56:06Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-3c47c93b74414c5f99ec260f7a2dc7322023-11-19T10:00:04ZengMDPI AGCells2073-44092023-09-011218229810.3390/cells12182298The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial CellsAnna Lindblad0Rongrong Wu1Katarina Persson2Isak Demirel3School of Medical Sciences, Örebro University, 701 82 Örebro, SwedenSchool of Medical Sciences, Örebro University, 701 82 Örebro, SwedenSchool of Medical Sciences, Örebro University, 701 82 Örebro, SwedenSchool of Medical Sciences, Örebro University, 701 82 Örebro, SwedenThe 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.https://www.mdpi.com/2073-4409/12/18/2298NLRP3 inflammasomeestradiolantimicrobial peptidesuropathogenic <i>Escherichia coli</i>urinary tract infections |
| spellingShingle | Anna Lindblad Rongrong Wu Katarina Persson Isak Demirel The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells Cells NLRP3 inflammasome estradiol antimicrobial peptides uropathogenic <i>Escherichia coli</i> urinary tract infections |
| 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 | NLRP3 inflammasome estradiol antimicrobial peptides uropathogenic <i>Escherichia coli</i> urinary tract infections |
| url | https://www.mdpi.com/2073-4409/12/18/2298 |
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