Publikation:

Inhibitor of Apoptosis Protein-1 Regulates Tumor Necrosis Factor-mediated Destruction of Intestinal Epithelial Cells

Lade...
Vorschaubild

Dateien

Grabinger_0-383915.pdf
Grabinger_0-383915.pdfGröße: 1.93 MBDownloads: 559

Datum

2017

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

ArXiv-ID

Internationale Patentnummer

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Green
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Gastroenterology. 2017, 152(4), pp. 867-879. ISSN 0016-5085. eISSN 1528-0012. Available under: doi: 10.1053/j.gastro.2016.11.019

Zusammenfassung

Background and aims

Tumor necrosis factor (TNF) is a cytokine that promotes inflammation and contributes to pathogenesis of inflammatory bowel diseases. Unlike other cells and tissues, intestinal epithelial cells undergo rapid cell death upon exposure to TNF, by unclear mechanisms. We investigated the roles of inhibitor of apoptosis proteins (IAPs) in the regulation of TNF-induced cell death in the intestinal epithelium of mice and intestinal organoids.

Methods

RNA from cell lines and tissues and analyzed by quantitative PCR, protein levels were analyzed by immunoblot assays. BIRC2 (also called cIAP1) was expressed upon induction from lentiviral vectors in young adult mouse colon (YAMC) cells. YAMC cells, the mouse colon carcinoma cell line MC38, the mouse macrophage cell line RAW 264.7, or mouse and human organoids were incubated with Smac-mimetic compound LCL161 or recombinant TNF-like weak inducer of apoptosis (TNFSF12) along with TNF, and cell death was quantified. C57BL/6 mice with disruption of Xiap,Birc2 (encodes cIAP1), Birc3 (encodes cIAP2), Tnfrsf1a, or Tnfrsf1b (Tnfrsf1a and b encode TNF receptors) were injected with TNF or saline (control); liver and intestinal tissues were collected and analyzed for apoptosis induction by cleaved caspase 3 immunohistochemistry. We also measured levels of TNF and alanine aminotransferase in serum from mice.

Results

YAMC cells, and mouse and human intestinal organoids, died rapidly in response to TNF. YAMC and intestinal crypts expressed lower levels of XIAP, cIAP1, cIAP2, and cFLIP than liver tissue. Smac-mimetics reduced levels of cIAP1 and XIAP in MC38 and YAMC cells, and Smac-mimetics and TWEAK increased TNF-induced cell death in YAMC cells and organoids—most likely by sequestering and degrading cIAP1. Injection of TNF greatly increased levels of cell death in intestinal tissue of cIAP1-null mice, compared to wild-type C57BL/6 mice, cIAP2-null mice, or XIAP-null mice. Excessive TNF-induced cell death in the intestinal epithelium was mediated TNF receptor 1.

Conclusion

In a study of mouse and human cell lines, organoids, and tissues, we found cIAP1 to be required for regulation of TNF-induced intestinal epithelial cell death and survival. These findings have important implications for the pathogenesis of TNF-mediated enteropathies and chronic inflammatory diseases of the intestine.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

TWEAK; TNF signaling; IBD; mouse model

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690GRABINGER, Thomas, Konstantin J. BODE, Janine DEMGENSKI, Carina SEITZ, M. Eugenia DELGADO, Feodora KOSTADINOVA, Cindy REINHOLD, Nima ETEMADI, Christof R. HAUCK, Thomas BRUNNER, 2017. Inhibitor of Apoptosis Protein-1 Regulates Tumor Necrosis Factor-mediated Destruction of Intestinal Epithelial Cells. In: Gastroenterology. 2017, 152(4), pp. 867-879. ISSN 0016-5085. eISSN 1528-0012. Available under: doi: 10.1053/j.gastro.2016.11.019
BibTex
@article{Grabinger2017-03Inhib-36485,
  year={2017},
  doi={10.1053/j.gastro.2016.11.019},
  title={Inhibitor of Apoptosis Protein-1 Regulates Tumor Necrosis Factor-mediated Destruction of Intestinal Epithelial Cells},
  number={4},
  volume={152},
  issn={0016-5085},
  journal={Gastroenterology},
  pages={867--879},
  author={Grabinger, Thomas and Bode, Konstantin J. and Demgenski, Janine and Seitz, Carina and Delgado, M. Eugenia and Kostadinova, Feodora and Reinhold, Cindy and Etemadi, Nima and Hauck, Christof R. and Brunner, Thomas}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/36485">
    <dc:contributor>Brunner, Thomas</dc:contributor>
    <dc:creator>Delgado, M. Eugenia</dc:creator>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/36485"/>
    <dc:creator>Kostadinova, Feodora</dc:creator>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/36485/1/Grabinger_0-383915.pdf"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-01-04T07:57:59Z</dcterms:available>
    <dc:contributor>Bode, Konstantin J.</dc:contributor>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>Delgado, M. Eugenia</dc:contributor>
    <dcterms:title>Inhibitor of Apoptosis Protein-1 Regulates Tumor Necrosis Factor-mediated Destruction of Intestinal Epithelial Cells</dcterms:title>
    <dc:rights>terms-of-use</dc:rights>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-01-04T07:57:59Z</dc:date>
    <dc:creator>Seitz, Carina</dc:creator>
    <dc:creator>Bode, Konstantin J.</dc:creator>
    <dc:contributor>Reinhold, Cindy</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/36485/1/Grabinger_0-383915.pdf"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Kostadinova, Feodora</dc:contributor>
    <dc:creator>Hauck, Christof R.</dc:creator>
    <dcterms:issued>2017-03</dcterms:issued>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Seitz, Carina</dc:contributor>
    <dcterms:abstract xml:lang="eng">Background and aims&lt;br /&gt;&lt;br /&gt;Tumor necrosis factor (TNF) is a cytokine that promotes inflammation and contributes to pathogenesis of inflammatory bowel diseases. Unlike other cells and tissues, intestinal epithelial cells undergo rapid cell death upon exposure to TNF, by unclear mechanisms. We investigated the roles of inhibitor of apoptosis proteins (IAPs) in the regulation of TNF-induced cell death in the intestinal epithelium of mice and intestinal organoids.&lt;br /&gt;&lt;br /&gt;Methods&lt;br /&gt;&lt;br /&gt;RNA from cell lines and tissues and analyzed by quantitative PCR, protein levels were analyzed by immunoblot assays. BIRC2 (also called cIAP1) was expressed upon induction from lentiviral vectors in young adult mouse colon (YAMC) cells. YAMC cells, the mouse colon carcinoma cell line MC38, the mouse macrophage cell line RAW 264.7, or mouse and human organoids were incubated with Smac-mimetic compound LCL161 or recombinant TNF-like weak inducer of apoptosis (TNFSF12) along with TNF, and cell death was quantified. C57BL/6 mice with disruption of Xiap,Birc2 (encodes cIAP1), Birc3 (encodes cIAP2), Tnfrsf1a, or Tnfrsf1b (Tnfrsf1a and b encode TNF receptors) were injected with TNF or saline (control); liver and intestinal tissues were collected and analyzed for apoptosis induction by cleaved caspase 3 immunohistochemistry. We also measured levels of TNF and alanine aminotransferase in serum from mice.&lt;br /&gt;&lt;br /&gt;Results&lt;br /&gt;&lt;br /&gt;YAMC cells, and mouse and human intestinal organoids, died rapidly in response to TNF. YAMC and intestinal crypts expressed lower levels of XIAP, cIAP1, cIAP2, and cFLIP than liver tissue. Smac-mimetics reduced levels of cIAP1 and XIAP in MC38 and YAMC cells, and Smac-mimetics and TWEAK increased TNF-induced cell death in YAMC cells and organoids—most likely by sequestering and degrading cIAP1. Injection of TNF greatly increased levels of cell death in intestinal tissue of cIAP1-null mice, compared to wild-type C57BL/6 mice, cIAP2-null mice, or XIAP-null mice. Excessive TNF-induced cell death in the intestinal epithelium was mediated TNF receptor 1.&lt;br /&gt;&lt;br /&gt;Conclusion&lt;br /&gt;&lt;br /&gt;In a study of mouse and human cell lines, organoids, and tissues, we found cIAP1 to be required for regulation of TNF-induced intestinal epithelial cell death and survival. These findings have important implications for the pathogenesis of TNF-mediated enteropathies and chronic inflammatory diseases of the intestine.</dcterms:abstract>
    <dc:creator>Brunner, Thomas</dc:creator>
    <dc:contributor>Grabinger, Thomas</dc:contributor>
    <dc:creator>Reinhold, Cindy</dc:creator>
    <dc:creator>Demgenski, Janine</dc:creator>
    <dc:language>eng</dc:language>
    <dc:contributor>Demgenski, Janine</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Grabinger, Thomas</dc:creator>
    <dc:contributor>Hauck, Christof R.</dc:contributor>
    <dc:contributor>Etemadi, Nima</dc:contributor>
    <dc:creator>Etemadi, Nima</dc:creator>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen