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...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 6, 2018
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| In: |
PLoS Computational Biology
Year: 2018, Volume: 14, Issue: 11 |
| ISSN: | 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1006582 |
| Online Access: | 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 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 11.03.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1006582 |