Abstract

Objectives: Progressive lung disease, driven by inflammation secondary to chronicbacterial infection, constitutes the chief burden of CF.We describe a systems biologyinvestigation of the pathogenesis of Pseudomonas aeruginosa infected CF airwaysaiming to identify biomarkers/pathways as potential targets for improved therapyor for use as prognostic indicators.Methods: We employed multi-dimensional LC-MS/MS to semi-quantitatively contrastthe cellular protein profiles of sputum from CF and control cohorts. Importantly,our approach effectively assesses the activity of CF cells directly in theirin vivo environment, so taking into account the interactions between host and thehighly complex CF microbiome.Results: 119 of the 2309 human proteins detected were common to all samples(36 CF + 12 control). Of these, 49 were down-regulated and 29 up-regulatedin CF (p<0.05). Additionally, 21 proteins were detected exclusively in all CFsamples and 17 proteins exclusively in all controls. Analysis for biological relevanceusing Ingenuity Pathway Analysis (IPA) software identified molecular and cellularfunctions belonging to the categories of Cell Death; Cellular Movement; ProteinSynthesis, Degradation, Trafficking & Post-Translational Modification; Cell-to-CellSignalling and Interaction; Free Radical Scavenging; and Cellular Assembly andOrganisation as divergent between the study cohorts.Conclusions: Comparison of the infected CF cellular proteome with IPA diseaseprofiles showed up-regulation of proteins previously identified in Respiratory, Immunologicaland Inflammatory Diseases, and down-regulation of proteins associatedwith Cancer and Neurological Disease.