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

Authors :
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
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

Subjects :
Biology (General)
QH301-705.5

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