Model-Based Characterization of Inflammatory Gene Expression Patterns of Activated Macrophages


Macrophages are cells with remarkable plasticity. They integrate signals from their microenvironment leading to context-dependent polarization into classically (M1) or alternatively (M2) activated macrophages, representing two extremes of a broad spectrum of divergent phenotypes. Thereby, macrophages deliver protective and pro-regenerative signals towards injured tissue but, depending on the eliciting damage, may also be responsible for the generation and aggravation of tissue injury. Although incompletely understood, there is emerging evidence that macrophage polarization is critical for these antagonistic roles. To identify activation-specific expression patterns of chemokines and cytokines that may confer these distinct effects a systems biology approach was applied. A comprehensive literature-based Boolean model was developed to describe the M1 (LPS-activated) and M2 (IL-4/13-activated) polarization types. The model was validated using high-throughput transcript expression data from murine bone marrow derived macrophages. By dynamic modeling of gene expression, the chronology of pathway activation and autocrine signaling was estimated. Our results provide a deepened understanding of the physiological balance leading to M1/M2 activation, indicating the relevance of co-regulatory signals at the level of Akt1 or Akt2 that may be important for directing macrophage polarization.


Projects: B1: Intercellular communication of hepatocytes and macrophages

PLoS Comput Biol
PLoS Comput Biol 12(7) : e1005018
27th Jul 2016

Julia Rex, Ute Albrecht, Christian Ehlting, Maria Thomas, Ulrich M. Zanger, Oliver Sawodny, Dieter Häussinger, Michael Ederer, Ronny Feuer, Johannes G. Bode

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[Julia Sanwald] [Ute Albrecht] [Maria Thomas] [Ulrich Zanger] [Oliver Sawodny]

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Cell and Intercellular
Views: 525
  • Created: 23rd Nov 2016 at 13:29
  • Last updated: 23rd Nov 2016 at 13:32

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