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A computational analysis of dynamic, multi-organ inflammatory crosstalk induced by endotoxin in mice.
- Source :
- PLoS Computational Biology, Vol 14, Iss 11, p e1006582 (2018)
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- 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.
- Subjects :
- Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 1553734X and 15537358
- Volume :
- 14
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Computational Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2c79d14110ca4cbabb9e7f8fb7d266e2
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1006582