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Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

Namas, RA and Bartels, J and Hoffman, R and Barclay, D and Billiar, TR and Zamora, R and Vodovotz, Y (2013) Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice. PLoS ONE, 8 (7).

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Abstract

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Namas, RAran39@pitt.eduRAN390000-0002-8582-5321
Bartels, J
Hoffman, Rrah10@pitt.eduRAH10
Barclay, Ddeb7@pitt.eduDEB7
Billiar, TRbilliar@pitt.eduBILLIAR
Zamora, Rzamorar@pitt.eduZAMORAR
Vodovotz, Yvodovotz@pitt.eduVODOVOTZ
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorUnutmaz, DeryaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 2 July 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0067419
Schools and Programs: Dietrich School of Arts and Sciences > Mathematics
Refereed: Yes
Other ID: NLM PMC3699569
PubMed Central ID: PMC3699569
PubMed ID: 23844008
Date Deposited: 16 Aug 2013 20:47
Last Modified: 04 Feb 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/19502

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