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DC Field | Value | Language |
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dc.contributor.author | Scicluna, Brendon P. | - |
dc.contributor.author | Veer, Cornelis Van't | - |
dc.contributor.author | Nieuwdorp, Max | - |
dc.contributor.author | Felsmann, Karen | - |
dc.contributor.author | Wlotzka, Britta | - |
dc.contributor.author | Stroes, Erik S.G. | - |
dc.contributor.author | Poll, Tom van der | - |
dc.date.accessioned | 2022-06-11T09:38:45Z | - |
dc.date.available | 2022-06-11T09:38:45Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Scicluna, B. P., van't Veer, C., Nieuwdorp, M., Felsmann, K., Wlotzka, B., Stroes, E. S., & van der Poll, T. (2013). Role of tumor necrosis factor-α in the human systemic endotoxin-induced transcriptome. PLoS One, 8(11), e79051. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/97570 | - |
dc.description.abstract | TNFα has been implicated in the pathogenesis of various inflammatory diseases. Different strategies to inhibit TNFα in patients with sepsis and chronic inflammatory conditions have shown contrasting outcomes. Although TNFα inhibitors are widely used in clinical practice, the impact of TNFα antagonism on white blood cell gene expression profiles during acute inflammation in humans in vivo has not been assessed. We here leveraged the established model of human endotoxemia to examine the effect of the TNFα antagonist, etanercept, on the genome-wide transcriptional responses in circulating leukocytes induced by intravenous LPS administration in male subjects. Etanercept pre-treatment resulted in a markedly dampened transcriptional response to LPS. Gene co-expression network analysis revealed this LPS-induced transcriptome can be categorized as TNFα responsive and non-responsive modules. Highly significant TNFα responsive modules include NF-kB signaling, antiviral responses and T-cell mediated responses. Within these TNFα responsive modules we delineate fundamental genes involved in epigenetic modifications, transcriptional initiation and elongation. Thus, we provide comprehensive information about molecular pathways that might be targeted by therapeutic interventions that seek to inhibit TNFα activity during human inflammatory diseases. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | PloS | en_GB |
dc.rights | info:eu-repo/semantics/openAccess | en_GB |
dc.subject | Epigenetics | en_GB |
dc.subject | Gene regulatory networks | en_GB |
dc.subject | Endotoxins -- Analysis | en_GB |
dc.subject | Tumor necrosis factor -- Receptors | en_GB |
dc.title | Role of tumor necrosis factor-α in the human systemic endotoxin-induced transcriptome | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1371/journal.pone.0079051 | - |
dc.publication.title | PLoS One | en_GB |
Appears in Collections: | Scholarly Works - FacHScABS |
Files in This Item:
File | Description | Size | Format | |
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Role_of_tumor_necrosis_factor_α_in_the_human_systemic_endotoxin_induced_transcriptome.pdf | 1.49 MB | Adobe PDF | View/Open |
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