Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In Vitro
Understanding how uropathogenic <i>Escherichia coli</i> (UPEC) modulates the immune response in the kidney is essential to prevent UPEC from reaching the bloodstream and causing urosepsis. The purpose of this study was to elucidate if renal fibroblasts can release IL-1β during a UPEC inf...
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2021-12-01
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author | Ashok Kumar Kumawat Geena Varghese Paramel Kartheyaene Jayaprakash Demirel Isak Demirel |
author_facet | Ashok Kumar Kumawat Geena Varghese Paramel Kartheyaene Jayaprakash Demirel Isak Demirel |
author_sort | Ashok Kumar Kumawat |
collection | DOAJ |
description | Understanding how uropathogenic <i>Escherichia coli</i> (UPEC) modulates the immune response in the kidney is essential to prevent UPEC from reaching the bloodstream and causing urosepsis. The purpose of this study was to elucidate if renal fibroblasts can release IL-1β during a UPEC infection and to investigate the mechanism behind the IL-1β release. We found that the UPEC strain CFT073 induced an increased IL-1β and LDH release from renal fibroblasts, but not from renal epithelial cells. The UPEC-induced IL-1β release was found to be NLRP3, caspase-1, caspase-4, ERK 1/2, cathepsin B and serine protease dependent in renal fibroblasts. We also found that the UPEC virulence factor α-hemolysin was necessary for IL-1β release. Conditioned medium from caspase-1, caspase-4 and NLRP3-deficient renal fibroblasts mediated an increased reactive oxygen species production from neutrophils, but reduced UPEC phagocytosis. Taken together, our study demonstrates that renal fibroblasts, but not renal epithelial cells, release IL-1β during a UPEC infection. This suggest that renal fibroblasts are vital immunoreactive cells and not only structural cells that produce and regulate the extracellular matrix. |
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issn | 2073-4409 |
language | English |
last_indexed | 2024-03-10T04:25:46Z |
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spelling | doaj.art-65470069fa564e9b8b7d45d7958aa8aa2023-11-23T07:38:56ZengMDPI AGCells2073-44092021-12-011012352210.3390/cells10123522Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In VitroAshok Kumar Kumawat0Geena Varghese Paramel1Kartheyaene Jayaprakash Demirel2Isak Demirel3Cardiovascular Research Center, Faculty of Medicine and Health, Örebro University, 701 82 Örebro, SwedenCardiovascular Research Center, Faculty of Medicine and Health, Örebro University, 701 82 Örebro, SwedenPublic Dental Service, Region Örebro County, 703 64 Örebro, SwedenSchool of Medical Sciences, Örebro University, 701 82 Örebro, SwedenUnderstanding how uropathogenic <i>Escherichia coli</i> (UPEC) modulates the immune response in the kidney is essential to prevent UPEC from reaching the bloodstream and causing urosepsis. The purpose of this study was to elucidate if renal fibroblasts can release IL-1β during a UPEC infection and to investigate the mechanism behind the IL-1β release. We found that the UPEC strain CFT073 induced an increased IL-1β and LDH release from renal fibroblasts, but not from renal epithelial cells. The UPEC-induced IL-1β release was found to be NLRP3, caspase-1, caspase-4, ERK 1/2, cathepsin B and serine protease dependent in renal fibroblasts. We also found that the UPEC virulence factor α-hemolysin was necessary for IL-1β release. Conditioned medium from caspase-1, caspase-4 and NLRP3-deficient renal fibroblasts mediated an increased reactive oxygen species production from neutrophils, but reduced UPEC phagocytosis. Taken together, our study demonstrates that renal fibroblasts, but not renal epithelial cells, release IL-1β during a UPEC infection. This suggest that renal fibroblasts are vital immunoreactive cells and not only structural cells that produce and regulate the extracellular matrix.https://www.mdpi.com/2073-4409/10/12/3522UPEChuman renal fibroblastsinflammasomeUTIIL-1β |
spellingShingle | Ashok Kumar Kumawat Geena Varghese Paramel Kartheyaene Jayaprakash Demirel Isak Demirel Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In Vitro Cells UPEC human renal fibroblasts inflammasome UTI IL-1β |
title | Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In Vitro |
title_full | Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In Vitro |
title_fullStr | Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In Vitro |
title_full_unstemmed | Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In Vitro |
title_short | Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic <i>Escherichia coli</i> Infection In Vitro |
title_sort | human renal fibroblasts but not renal epithelial cells induce il 1β release during a uropathogenic i escherichia coli i infection in vitro |
topic | UPEC human renal fibroblasts inflammasome UTI IL-1β |
url | https://www.mdpi.com/2073-4409/10/12/3522 |
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