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Transcriptome analysis revealed unique genes as targets for the anti-inflammatory action of activated protein C in human macrophages


Pereira, C P; Bachli, E B; Schaer, D J; Schoedon, G (2010). Transcriptome analysis revealed unique genes as targets for the anti-inflammatory action of activated protein C in human macrophages. PLoS ONE, 5(10):e15352.

Abstract

BACKGROUND: Activated protein C (APC) has been introduced as a therapeutic agent for treatment of patients with severe sepsis due to its unique anticoagulant and anti-inflammatory properties in the vascular system. In this study we investigated novel targets for the anti-inflammatory action of APC in human macrophages.
METHODS: Using a genome-wide approach, effects of APC on the expression profile in inflammatory activated human macrophages were analyzed.
RESULTS: We identified, for the first time, genes that are specifically regulated by APC under inflammatory conditions, such as chromatin binding protein 4B (CHMP4B) and p300/CBP-associated factor (PCAF), thus indicating a role of APC in the epigenetic control of gene transcription. A functional assay showed the influence of APC in the acetyltransferase/deacetylase activity of nuclear extracts from inflamed macrophages.
CONCLUSION: Our data sheds new light on APC targets in inflammation and opens new lines of investigation that may be explored in order to further elucidate its unique molecule properties.

BACKGROUND: Activated protein C (APC) has been introduced as a therapeutic agent for treatment of patients with severe sepsis due to its unique anticoagulant and anti-inflammatory properties in the vascular system. In this study we investigated novel targets for the anti-inflammatory action of APC in human macrophages.
METHODS: Using a genome-wide approach, effects of APC on the expression profile in inflammatory activated human macrophages were analyzed.
RESULTS: We identified, for the first time, genes that are specifically regulated by APC under inflammatory conditions, such as chromatin binding protein 4B (CHMP4B) and p300/CBP-associated factor (PCAF), thus indicating a role of APC in the epigenetic control of gene transcription. A functional assay showed the influence of APC in the acetyltransferase/deacetylase activity of nuclear extracts from inflamed macrophages.
CONCLUSION: Our data sheds new light on APC targets in inflammation and opens new lines of investigation that may be explored in order to further elucidate its unique molecule properties.

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2 citations in Web of Science®
3 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:01 Feb 2011 15:58
Last Modified:05 Jul 2016 11:49
Publisher:Public Library of Science (PLoS)
ISSN:1932-6203
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1371/journal.pone.0015352
PubMed ID:20976180
Permanent URL: http://doi.org/10.5167/uzh-44232

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