| A dynamic view of trauma/hemorrhage-induced inflammation in mice: principal drivers and networks. | |
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MedLine Citation:
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PMID: 21573002 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: Complex biological processes such as acute inflammation induced by trauma/hemorrhagic shock/ (T/HS) are dynamic and multi-dimensional. We utilized multiplexing cytokine analysis coupled with data-driven modeling to gain a systems perspective into T/HS. METHODOLOGY/PRINCIPAL FINDINGS: Mice were subjected to surgical cannulation trauma (ST) ± hemorrhagic shock (HS; 25 mmHg), and followed for 1, 2, 3, or 4 h in each case. Serum was assayed for 20 cytokines and NO(2) (-)/NO(3) (-). These data were analyzed using four data-driven methods (Hierarchical Clustering Analysis [HCA], multivariate analysis [MA], Principal Component Analysis [PCA], and Dynamic Network Analysis [DyNA]). Using HCA, animals subjected to ST vs. ST + HS could be partially segregated based on inflammatory mediator profiles, despite a large overlap. Based on MA, interleukin [IL]-12p40/p70 (IL-12.total), monokine induced by interferon-γ (CXCL-9) [MIG], and IP-10 were the best discriminators between ST and ST/HS. PCA suggested that the inflammatory mediators found in the three main principal components in animals subjected to ST were IL-6, IL-10, and IL-13, while the three principal components in ST + HS included a large number of cytokines including IL-6, IL-10, keratinocyte-derived cytokine (CXCL-1) [KC], and tumor necrosis factor-α [TNF-α]. DyNA suggested that the circulating mediators produced in response to ST were characterized by a high degree of interconnection/complexity at all time points; the response to ST + HS consisted of different central nodes, and exhibited zero network density over the first 2 h with lesser connectivity vs. ST at all time points. DyNA also helped link the conclusions from MA and PCA, in that central nodes consisting of IP-10 and IL-12 were seen in ST, while MIG and IL-6 were central nodes in ST + HS. CONCLUSIONS/SIGNIFICANCE: These studies help elucidate the dynamics of T/HS-induced inflammation, complementing other forms of dynamic mechanistic modeling. These methods should be applicable to the analysis of other complex biological processes. |
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Authors:
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Qi Mi; Gregory Constantine; Cordelia Ziraldo; Alexey Solovyev; Andres Torres; Rajaie Namas; Timothy Bentley; Timothy R Billiar; Ruben Zamora; Juan Carlos Puyana; Yoram Vodovotz |
Publication Detail:
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Type: Journal Article Date: 2011-05-10 |
Journal Detail:
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Title: PloS one Volume: 6 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2011 |
Date Detail:
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Created Date: 2011-05-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e19424 Citation Subset: IM |
Affiliation:
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Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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