Identification of signaling components required for the prediction of cytokine release in RAW 264.7 macrophages

Genome Biology
Sylvain PradervandShankar Subramaniam

Abstract

Release of immuno-regulatory cytokines and chemokines during inflammatory response is mediated by a complex signaling network. Multiple stimuli produce different signals that generate different cytokine responses. Current knowledge does not provide a complete picture of these signaling pathways. However, using specific markers of signaling pathways, such as signaling proteins, it is possible to develop a 'coarse-grained network' map that can help understand common regulatory modules for various cytokine responses and help differentiate between the causes of their release. Using a systematic profiling of signaling responses and cytokine release in RAW 264.7 macrophages made available by the Alliance for Cellular Signaling, an analysis strategy is presented that integrates principal component regression and exhaustive search-based model reduction to identify required signaling factors necessary and sufficient to predict the release of seven cytokines (G-CSF, IL-1alpha, IL-6, IL-10, MIP-1alpha, RANTES, and TNFalpha) in response to selected ligands. This study provides a model-based quantitative estimate of cytokine release and identifies ten signaling components involved in cytokine production. The models identified capture many o...Continue Reading

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Aug 19, 2011·Journal of Clinical Immunology·Oliver CrespoWilliam H Robinson
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Jun 3, 2009·Biophysical Journal·Shakti GuptaShankar Subramaniam

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