Systems approaches to modeling chronic mucosal inflammation

Mridul Kalita, Bing Tian, Boning Gao, Sanjeev Choudhary, Thomas Wood, Joseph R. Carmical, Istvan Boldogh, Sankar Mitra, John D. Minna, Allan R. Brasier

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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-B pathways. Simulation experiments demonstrate that rapid, coordinated cap-independent translation of TRAF-1 and NF-B2 is required to reduce the noncanonical pathway coupling interval. Experiments using amantadine confirmed the prediction that TRAF-1 and NF-B2/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.

Original languageEnglish (US)
Article number505864
JournalBioMed Research International
Volume2013
DOIs
StatePublished - 2013

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Epithelial-Mesenchymal Transition
Inflammation
Amantadine
Pulmonary diseases
Gene expression
Epigenomics
Experiments
Chemical activation
Epithelial Cells
Phenotype
Respiratory Mucosa
Gene Regulatory Networks
Gene Expression Profiling
Proteomics
Chronic Obstructive Pulmonary Disease
Chronic Disease
Asthma
Mucous Membrane

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Kalita, M., Tian, B., Gao, B., Choudhary, S., Wood, T., Carmical, J. R., ... Brasier, A. R. (2013). Systems approaches to modeling chronic mucosal inflammation. BioMed Research International, 2013, [505864]. https://doi.org/10.1155/2013/505864

Systems approaches to modeling chronic mucosal inflammation. / Kalita, Mridul; Tian, Bing; Gao, Boning; Choudhary, Sanjeev; Wood, Thomas; Carmical, Joseph R.; Boldogh, Istvan; Mitra, Sankar; Minna, John D.; Brasier, Allan R.

In: BioMed Research International, Vol. 2013, 505864, 2013.

Research output: Contribution to journalArticle

Kalita, M, Tian, B, Gao, B, Choudhary, S, Wood, T, Carmical, JR, Boldogh, I, Mitra, S, Minna, JD & Brasier, AR 2013, 'Systems approaches to modeling chronic mucosal inflammation', BioMed Research International, vol. 2013, 505864. https://doi.org/10.1155/2013/505864
Kalita, Mridul ; Tian, Bing ; Gao, Boning ; Choudhary, Sanjeev ; Wood, Thomas ; Carmical, Joseph R. ; Boldogh, Istvan ; Mitra, Sankar ; Minna, John D. ; Brasier, Allan R. / Systems approaches to modeling chronic mucosal inflammation. In: BioMed Research International. 2013 ; Vol. 2013.
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