Next Article in Journal
Special Issue “Feature Papers”
Next Article in Special Issue
A Computational Study of the Effects of Syk Activity on B Cell Receptor Signaling Dynamics
Previous Article in Journal
Special Issue: Design of Bioreactor Systems for Tissue Engineering
Previous Article in Special Issue
Mathematical Modeling of Pro- and Anti-Inflammatory Signaling in Macrophages
Article Menu

Export Article

Open AccessArticle
Processes 2015, 3(1), 50-70; doi:10.3390/pr3010050

Modeling the Dynamics of Acute Phase Protein Expression in Human Hepatoma Cells Stimulated by IL-6

1
Department of Chemical Engineering, Villanova University, Villanova, PA 19085, USA
2
Department of Mechanical Engineering, Villanova University, Villanova, PA 19085, USA
3
The Center for Nonlinear Dynamics& Control (CENDAC), Villanova University, Villanova, PA 19085, USA
4
The Villanova Center for the Advancement of Sustainability in Engineering (VCASE), Villanova University, Villanova, PA 19085, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Juergen Hahn
Received: 22 August 2014 / Accepted: 9 December 2014 / Published: 14 January 2015
(This article belongs to the Special Issue Modeling and Analysis of Signal Transduction Networks)
View Full-Text   |   Download PDF [2825 KB, uploaded 14 January 2015]   |  

Abstract

Interleukin-6 (IL-6) is a systemic inflammatory mediator that triggers the human body’s acute phase response to trauma or inflammation. Although mathematical models for IL-6 signaling pathways have previously been developed, reactions that describe the expression of acute phase proteins were not included. To address this deficiency, a recent model of IL-6 signaling was extended to predict the dynamics of acute phase protein expression in IL-6-stimulated HepG2 cells (a human hepatoma cell line). This included reactions that describe the regulation of haptoglobin, fibrinogen, and albumin secretion by nuclear transcription factors STAT3 dimer and C/EBPβ. This new extended model was validated against two different sets of experimental data. Using the validated model, a sensitivity analysis was performed to identify seven potential drug targets to regulate the secretion of haptoglobin, fibrinogen, and albumin. The drug-target binding kinetics for these seven targets was then integrated with the IL-6 kinetic model to rank them based upon the influence of their pairing with drugs on acute phase protein dynamics. It was found that gp80, JAK, and gp130 were the three most promising drug targets and that it was possible to reduce the therapeutic dosage by combining drugs aimed at the top three targets in a cocktail. These findings suggest hypotheses for further experimental investigation. View Full-Text
Keywords: systems engineering; cellular biology and engineering; kinetics; mathematical modeling; parameter estimation; sensitivity analysis systems engineering; cellular biology and engineering; kinetics; mathematical modeling; parameter estimation; sensitivity analysis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Xu, Z.; Karlsson, J.O.M.; Huang, Z. Modeling the Dynamics of Acute Phase Protein Expression in Human Hepatoma Cells Stimulated by IL-6. Processes 2015, 3, 50-70.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Processes EISSN 2227-9717 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top