Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Dreschers, Stephan, Platen, Christopher, Ludwig, Andreas, Gille, Christian, Köstlin, Natascha, Orlikowsky, Thorsten W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783412065517436928
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
work_keys_str_mv AT dreschersstephan metalloproteinasestaceandmmp9differentiallyregulatedeathfactorsonadultandneonatalmonocytesafterinfectionwithescherichiacoli
AT platenchristopher metalloproteinasestaceandmmp9differentiallyregulatedeathfactorsonadultandneonatalmonocytesafterinfectionwithescherichiacoli
AT ludwigandreas metalloproteinasestaceandmmp9differentiallyregulatedeathfactorsonadultandneonatalmonocytesafterinfectionwithescherichiacoli
AT gillechristian metalloproteinasestaceandmmp9differentiallyregulatedeathfactorsonadultandneonatalmonocytesafterinfectionwithescherichiacoli
AT kostlinnatascha metalloproteinasestaceandmmp9differentiallyregulatedeathfactorsonadultandneonatalmonocytesafterinfectionwithescherichiacoli
AT orlikowskythorstenw metalloproteinasestaceandmmp9differentiallyregulatedeathfactorsonadultandneonatalmonocytesafterinfectionwithescherichiacoli