Buchumschlag

A computational analysis of dynamic, multi-organ inflammatory crosstalk induced by endotoxin in mice

Bacterial lipopolysaccharide (LPS) induces an acute inflammatory response across multiple organs, primarily via Toll-like receptor 4 (TLR4). We sought to define novel aspects of the complex spatiotemporal dynamics of LPS-induced inflammation using computational modeling, with a special focus on the...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Zamora, Ruben (VerfasserIn) , Korff, Sebastian (VerfasserIn) , Mi, Qi (VerfasserIn) , Barclay, Derek (VerfasserIn) , Schimunek, Lukas (VerfasserIn) , Zucca, Riccardo (VerfasserIn) , Arsiwalla, Xerxes D. (VerfasserIn) , Simmons, Richard L. (VerfasserIn) , Verschure, Paul (VerfasserIn) , Billiar, Timothy R. (VerfasserIn) , Vodovotz, Yoram (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: November 6, 2018
In: PLoS Computational Biology
Year: 2018, Jahrgang: 14, Heft: 11
ISSN:1553-7358
DOI:10.1371/journal.pcbi.1006582
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pcbi.1006582
Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006582
Volltext
Verfasserangaben:Ruben Zamora, Sebastian Korff, Qi Mi, Derek Barclay, Lukas Schimunek, Riccardo Zucca, Xerxes D. Arsiwalla, Richard L. Simmons, Paul Verschure, Timothy R. Billiar, Yoram Vodovotz
Beschreibung
Zusammenfassung:Bacterial lipopolysaccharide (LPS) induces an acute inflammatory response across multiple organs, primarily via Toll-like receptor 4 (TLR4). We sought to define novel aspects of the complex spatiotemporal dynamics of LPS-induced inflammation using computational modeling, with a special focus on the timing of pathological systemic spillover. An analysis of principal drivers of LPS-induced inflammation in the heart, gut, lung, liver, spleen, and kidney to assess organ-specific dynamics, as well as in the plasma (as an assessment of systemic spillover), was carried out using data on 20 protein-level inflammatory mediators measured over 0-48h in both C57BL/6 and TLR4-null mice. Using a suite of computational techniques, including a time-interval variant of Principal Component Analysis, we confirm key roles for cytokines such as tumor necrosis factor-α and interleukin-17A, define a temporal hierarchy of organ-localized inflammation, and infer the point at which organ-localized inflammation spills over systemically. Thus, by employing a systems biology approach, we obtain a novel perspective on the time- and organ-specific components in the propagation of acute systemic inflammation.
Beschreibung:Gesehen am 11.03.2020
Beschreibung:Online Resource
ISSN:1553-7358
DOI:10.1371/journal.pcbi.1006582

Ähnliche Einträge