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Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli
Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471605/ https://www.ncbi.nlm.nih.gov/pubmed/30897723 http://dx.doi.org/10.3390/ijms20061399 |
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author | Dreschers, Stephan Platen, Christopher Ludwig, Andreas Gille, Christian Köstlin, Natascha Orlikowsky, Thorsten W. |
author_facet | Dreschers, Stephan Platen, Christopher Ludwig, Andreas Gille, Christian Köstlin, Natascha Orlikowsky, Thorsten W. |
author_sort | Dreschers, Stephan |
collection | PubMed |
description | Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates. |
format | Online Article Text |
id | pubmed-6471605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64716052019-04-26 Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli Dreschers, Stephan Platen, Christopher Ludwig, Andreas Gille, Christian Köstlin, Natascha Orlikowsky, Thorsten W. Int J Mol Sci Article Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates. MDPI 2019-03-20 /pmc/articles/PMC6471605/ /pubmed/30897723 http://dx.doi.org/10.3390/ijms20061399 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dreschers, Stephan Platen, Christopher Ludwig, Andreas Gille, Christian Köstlin, Natascha Orlikowsky, Thorsten W. Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli |
title | Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli |
title_full | Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli |
title_fullStr | Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli |
title_full_unstemmed | Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli |
title_short | Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli |
title_sort | metalloproteinases tace and mmp-9 differentially regulate death factors on adult and neonatal monocytes after infection with escherichia coli |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471605/ https://www.ncbi.nlm.nih.gov/pubmed/30897723 http://dx.doi.org/10.3390/ijms20061399 |
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