Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Stan, Razvan C., Soriano, Francisco G., de Camargo, Maristela M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
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
_version_ 1783339117759692800
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
work_keys_str_mv AT stanrazvanc amathematicalmodelrelatesintracellulartlr4oscillationstosepsisprogression
AT sorianofranciscog amathematicalmodelrelatesintracellulartlr4oscillationstosepsisprogression
AT decamargomaristelam amathematicalmodelrelatesintracellulartlr4oscillationstosepsisprogression
AT stanrazvanc mathematicalmodelrelatesintracellulartlr4oscillationstosepsisprogression
AT sorianofranciscog mathematicalmodelrelatesintracellulartlr4oscillationstosepsisprogression
AT decamargomaristelam mathematicalmodelrelatesintracellulartlr4oscillationstosepsisprogression