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A mathematical model relates intracellular TLR4 oscillations to sepsis progression
OBJECTIVE: Oscillations of physiological parameters describe many biological processes and their modulation is determinant for various pathologies. In sepsis, toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its intracellular trafficking rates shift t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042260/ https://www.ncbi.nlm.nih.gov/pubmed/29996939 http://dx.doi.org/10.1186/s13104-018-3561-9 |
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author | Stan, Razvan C. Soriano, Francisco G. de Camargo, Maristela M. |
author_facet | Stan, Razvan C. Soriano, Francisco G. de Camargo, Maristela M. |
author_sort | Stan, Razvan C. |
collection | PubMed |
description | OBJECTIVE: Oscillations of physiological parameters describe many biological processes and their modulation is determinant for various pathologies. In sepsis, toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its intracellular trafficking rates shift the equilibrium between the pro- and anti-inflammatory downstream signaling cascades, leading to either the physiological resolution of the bacterial stimulation or to sepsis. This study aimed to evaluate the effects of TLR4 increased expression and intracellular trafficking on the course and outcome of sepsis. RESULTS: Using a set of three differential equations, we defined the TLR4 fluxes between relevant cell organelles. We obtained three different regions in the phase space: (1) a limit-cycle describing unstimulated physiological oscillations, (2) a fixed-point attractor resulting from moderate LPS stimulation that is resolved and (3) a double-attractor resulting from sustained LPS stimulation that leads to sepsis. We used this model to describe available hospital data of sepsis patients and we correctly characterize the clinical outcome of these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3561-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6042260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60422602018-07-13 A mathematical model relates intracellular TLR4 oscillations to sepsis progression Stan, Razvan C. Soriano, Francisco G. de Camargo, Maristela M. BMC Res Notes Research Note OBJECTIVE: Oscillations of physiological parameters describe many biological processes and their modulation is determinant for various pathologies. In sepsis, toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its intracellular trafficking rates shift the equilibrium between the pro- and anti-inflammatory downstream signaling cascades, leading to either the physiological resolution of the bacterial stimulation or to sepsis. This study aimed to evaluate the effects of TLR4 increased expression and intracellular trafficking on the course and outcome of sepsis. RESULTS: Using a set of three differential equations, we defined the TLR4 fluxes between relevant cell organelles. We obtained three different regions in the phase space: (1) a limit-cycle describing unstimulated physiological oscillations, (2) a fixed-point attractor resulting from moderate LPS stimulation that is resolved and (3) a double-attractor resulting from sustained LPS stimulation that leads to sepsis. We used this model to describe available hospital data of sepsis patients and we correctly characterize the clinical outcome of these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3561-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-11 /pmc/articles/PMC6042260/ /pubmed/29996939 http://dx.doi.org/10.1186/s13104-018-3561-9 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Note Stan, Razvan C. Soriano, Francisco G. de Camargo, Maristela M. A mathematical model relates intracellular TLR4 oscillations to sepsis progression |
title | A mathematical model relates intracellular TLR4 oscillations to sepsis progression |
title_full | A mathematical model relates intracellular TLR4 oscillations to sepsis progression |
title_fullStr | A mathematical model relates intracellular TLR4 oscillations to sepsis progression |
title_full_unstemmed | A mathematical model relates intracellular TLR4 oscillations to sepsis progression |
title_short | A mathematical model relates intracellular TLR4 oscillations to sepsis progression |
title_sort | mathematical model relates intracellular tlr4 oscillations to sepsis progression |
topic | Research Note |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042260/ https://www.ncbi.nlm.nih.gov/pubmed/29996939 http://dx.doi.org/10.1186/s13104-018-3561-9 |
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