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In Silico Simulation of Corticosteroids Effect on an NFkB-Dependent Physicochemical Model of Systemic

Summary: In Silico Simulation of Corticosteroids Effect on an NFkB-
Dependent Physicochemical Model of Systemic
Panagiota T. Foteinou1
, Steve E. Calvano2
, Stephen F. Lowry2
, Ioannis P. Androulakis1
1 Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America, 2 Department of Surgery, UMDNJ-Robert Wood Johnson Medical School,
New Brunswick, New Jersey, United States of America
Background: During the onset of an inflammatory response signaling pathways are activated for ``translating'' extracellular
signals into intracellular responses converging to the activation of nuclear factor (NF)-kB, a central transcription factor in
driving the inflammatory response. An inadequate control of its transcriptional activity is associated with the culmination of a
hyper-inflammatory response making it a desired therapeutic target. Predicated upon the nature of the response, a systems
level analysis might provide rational leads for the development of strategies that promote the resolution of the response.
Methodology and Findings: A physicochemical host response model is proposed to integrate biological information in the
form of kinetic rules and signaling cascades with pharmacokinetic models of drug action for the modulation of the response.
The unifying hypothesis is that the response is triggered by the activation of the NFkB signaling module and corticosteroids
serve as a template for assessing anti-inflammatory strategies. The proposed in silico model is evaluated through its ability to


Source: Androulakis, Ioannis (Yannis) - Biomedical Engineering Department & Department of Chemical and Biochemical Engineering, Rutgers University


Collections: Engineering; Biology and Medicine