Computational approach to characterize causative factors and molecular indicators of chronic wound inflammation.
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Date
2014-02-10
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Abstract
Chronic inflammation is rapidly becoming recognized as a key contributor to numerous pathologies Despite detailed investigations understanding of the molecular mechanisms regulating inflammation is incomplete Knowledge of such critical regulatory processes and informative indicators of chronic inflammation is necessary for efficacious therapeutic interventions and diagnostic support to clinicians We used a computational modeling approach to elucidate the critical factors responsible for chronic inflammation and to identify robust molecular indicators of chronic inflammatory conditions Our kinetic model successfully captured experimentally observed cell and cytokine dynamics for both acute and chronic inflammatory responses Using sensitivity analysis we identified macrophage influx and efflux rate modulation as the strongest inducing factor of chronic inflammation for a wide range of scenarios Moreover our model predicted that among all major inflammatory mediators IL 6 TGF and PDGF may generally be considered the most sensitive and robust indicators of chronic inflammation which is supported by existing but limited experimental evidence