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Mathematical modeling, which has been instrumental for understanding the NF-\u03baB response in other cell types, offers a valuable tool to investigate the regulation of NF-\u03baB activation in microglia at a systems level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We quantify the dynamic response of NF-\u03baB activation and activation of the upstream kinase IKK using ELISA measurements of a microglial cell line following treatment with the pro-inflammatory cytokine TNF\u03b1. A new mathematical model is developed based on these data sets using a modular procedure that exploits the feedback structure of the network. We show that the new model requires previously unmodeled dynamics involved in the stimulus-induced degradation of the inhibitor I\u03baB\u03b1 in order to properly describe microglial NF-\u03baB activation in a statistically consistent manner. This suggests a more prominent role for the ubiquitin-proteasome system in regulating the activation of NF-\u03baB to inflammatory stimuli. We also find that the introduction of nonlinearities in the kinetics of IKK activation and inactivation is essential for proper characterization of transient IKK activity and corresponds to known biological mechanisms. Numerical analyses of the model highlight key regulators of the microglial NF-\u03baB response, as well as those governing IKK activation. Results illustrate the dynamic regulatory mechanisms and the robust yet fragile nature of the negative feedback regulated network.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We have developed a new mathematical model that incorporates previously unmodeled dynamics to characterize the dynamic response of the NF-\u03baB signaling network in microglia. This model is the first of its kind for microglia and provides a tool for the quantitative, systems level study the dynamic cellular response to inflammatory stimuli.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-12-276","type":"journal-article","created":{"date-parts":[[2011,7,6]],"date-time":"2011-07-06T06:21:25Z","timestamp":1309933285000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Quantitative characterization and analysis of the dynamic NF-\u03baB response in microglia"],"prefix":"10.1186","volume":"12","author":[{"given":"Patrick W","family":"Sheppard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F","family":"Emery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rona G","family":"Giffard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa","family":"Khammash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,7,5]]},"reference":[{"issue":"6","key":"4717_CR1","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/S0166-2236(96)01035-1","volume":"20","author":"LA O'Neill","year":"1997","unstructured":"O'Neill LA, Kaltschmidt C: NF-\u03baB: a crucial transcription factor for glial and neuronal cell function. 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