Systems Approaches to Modeling Chronic Mucosal Inflammation
Joint Authors
Choudhary, Sanjeev
Kalita, Mridul
Tian, Bing
Gao, Boning
Wood, Thomas G.
Carmical, Joseph R.
Mitra, Sankar
Minna, John D.
Brasier, Allan R.
Boldogh, Istvan
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-10-21
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
The respiratory mucosa is a major coordinator of the inflammatory response in chronic airway diseases, including asthma and chronic obstructive pulmonary disease (COPD).
Signals produced by the chronic inflammatory process induce epithelial mesenchymal transition (EMT) that dramatically alters the epithelial cell phenotype.
The effects of EMT on epigenetic reprogramming and the activation of transcriptional networks are known, its effects on the innate inflammatory response are underexplored.
We used a multiplex gene expression profiling platform to investigate the perturbations of the innate pathways induced by TGFβ in a primary airway epithelial cell model of EMT.
EMT had dramatic effects on the induction of the innate pathway and the coupling interval of the canonical and noncanonical NF-κB pathways.
Simulation experiments demonstrate that rapid, coordinated cap-independent translation of TRAF-1 and NF-κB2 is required to reduce the noncanonical pathway coupling interval.
Experiments using amantadine confirmed the prediction that TRAF-1 and NF-κB2/p100 production is mediated by an IRES-dependent mechanism.
These data indicate that the epigenetic changes produced by EMT induce dynamic state changes of the innate signaling pathway.
Further applications of systems approaches will provide understanding of this complex phenotype through deterministic modeling and multidimensional (genomic and proteomic) profiling.
American Psychological Association (APA)
Kalita, Mridul& Tian, Bing& Gao, Boning& Choudhary, Sanjeev& Wood, Thomas G.& Carmical, Joseph R.…[et al.]. 2013. Systems Approaches to Modeling Chronic Mucosal Inflammation. BioMed Research International،Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-1030611
Modern Language Association (MLA)
Kalita, Mridul…[et al.]. Systems Approaches to Modeling Chronic Mucosal Inflammation. BioMed Research International No. 2013 (2013), pp.1-17.
https://search.emarefa.net/detail/BIM-1030611
American Medical Association (AMA)
Kalita, Mridul& Tian, Bing& Gao, Boning& Choudhary, Sanjeev& Wood, Thomas G.& Carmical, Joseph R.…[et al.]. Systems Approaches to Modeling Chronic Mucosal Inflammation. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-1030611
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030611