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Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver
Heat stroke (HS) is a life-threatening illness induced by prolonged exposure to a hot environment that causes central nervous system abnormalities and severe hyperthermia. Current data suggest that the pathophysiological responses to heat stroke may not only be due to the immediate effects of heat e...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764238/ https://www.ncbi.nlm.nih.gov/pubmed/24039931 http://dx.doi.org/10.1371/journal.pone.0073393 |
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author | Rodriguez-Fernandez, Maria Grosman, Benyamin Yuraszeck, Theresa M. Helwig, Bryan G. Leon, Lisa R. Doyle III, Francis J. |
author_facet | Rodriguez-Fernandez, Maria Grosman, Benyamin Yuraszeck, Theresa M. Helwig, Bryan G. Leon, Lisa R. Doyle III, Francis J. |
author_sort | Rodriguez-Fernandez, Maria |
collection | PubMed |
description | Heat stroke (HS) is a life-threatening illness induced by prolonged exposure to a hot environment that causes central nervous system abnormalities and severe hyperthermia. Current data suggest that the pathophysiological responses to heat stroke may not only be due to the immediate effects of heat exposure per se but also the result of a systemic inflammatory response syndrome (SIRS). The observation that pro- (e.g., IL-1) and anti-inflammatory (e.g., IL-10) cytokines are elevated concomitantly during recovery suggests a complex network of interactions involved in the manifestation of heat-induced SIRS. In this study, we measured a set of circulating cytokine/soluble cytokine receptor proteins and liver cytokine and receptor mRNA accumulation in wild-type and tumor necrosis factor (TNF) receptor knockout mice to assess the effect of neutralization of TNF signaling on the SIRS following HS. Using a systems approach, we developed a computational model describing dynamic changes (intra- and extracellular events) in the cytokine signaling pathways in response to HS that was fitted to novel genomic (liver mRNA accumulation) and proteomic (circulating cytokines and receptors) data using global optimization. The model allows integration of relevant biological knowledge and formulation of new hypotheses regarding the molecular mechanisms behind the complex etiology of HS that may serve as future therapeutic targets. Moreover, using our unique modeling framework, we explored cytokine signaling pathways with three in silico experiments (e.g. by simulating different heat insult scenarios and responses in cytokine knockout strains in silico). |
format | Online Article Text |
id | pubmed-3764238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37642382013-09-13 Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver Rodriguez-Fernandez, Maria Grosman, Benyamin Yuraszeck, Theresa M. Helwig, Bryan G. Leon, Lisa R. Doyle III, Francis J. PLoS One Research Article Heat stroke (HS) is a life-threatening illness induced by prolonged exposure to a hot environment that causes central nervous system abnormalities and severe hyperthermia. Current data suggest that the pathophysiological responses to heat stroke may not only be due to the immediate effects of heat exposure per se but also the result of a systemic inflammatory response syndrome (SIRS). The observation that pro- (e.g., IL-1) and anti-inflammatory (e.g., IL-10) cytokines are elevated concomitantly during recovery suggests a complex network of interactions involved in the manifestation of heat-induced SIRS. In this study, we measured a set of circulating cytokine/soluble cytokine receptor proteins and liver cytokine and receptor mRNA accumulation in wild-type and tumor necrosis factor (TNF) receptor knockout mice to assess the effect of neutralization of TNF signaling on the SIRS following HS. Using a systems approach, we developed a computational model describing dynamic changes (intra- and extracellular events) in the cytokine signaling pathways in response to HS that was fitted to novel genomic (liver mRNA accumulation) and proteomic (circulating cytokines and receptors) data using global optimization. The model allows integration of relevant biological knowledge and formulation of new hypotheses regarding the molecular mechanisms behind the complex etiology of HS that may serve as future therapeutic targets. Moreover, using our unique modeling framework, we explored cytokine signaling pathways with three in silico experiments (e.g. by simulating different heat insult scenarios and responses in cytokine knockout strains in silico). Public Library of Science 2013-09-05 /pmc/articles/PMC3764238/ /pubmed/24039931 http://dx.doi.org/10.1371/journal.pone.0073393 Text en © 2013 Rodriguez-Fernandez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rodriguez-Fernandez, Maria Grosman, Benyamin Yuraszeck, Theresa M. Helwig, Bryan G. Leon, Lisa R. Doyle III, Francis J. Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver |
title | Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver |
title_full | Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver |
title_fullStr | Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver |
title_full_unstemmed | Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver |
title_short | Modeling the Intra- and Extracellular Cytokine Signaling Pathway under Heat Stroke in the Liver |
title_sort | modeling the intra- and extracellular cytokine signaling pathway under heat stroke in the liver |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764238/ https://www.ncbi.nlm.nih.gov/pubmed/24039931 http://dx.doi.org/10.1371/journal.pone.0073393 |
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