title: Interactions between an inflammatory response to infection and protein trafficking pathways favor correction of defective protein trafficking in Cystic Fibrosis.
abstract: One unresolved issue in Cystic Fibrosis research is how functional loss of CFTR, a protein involved in chloride transport, results in chronic lung inflammation. Large scale experiments investigating protein or gene expression changes due to altered trafficking of the most common disease causing CFTR mutation (ΔF508) have produced long lists of changes with no apparent connection to inflammation. Likewise, experiments documenting the effects of inflammation in bronchial epithelial cell lines have yielded no insights into CFTR trafficking. We used MetaMiner CF to combine and analyze results of several CFTR trafficking and epithelial response to infection studies which were on different platforms using different methodologies and had different objectives. The program searches a manually curated database for published experiments linking proteins or genes and displays the interactions in a more easily understood graphic format. Numerous connections were established between genes documented to correct ΔF508 trafficking and a list of genes differentially expressed in bronchial epithelial cells after exposure to bacteria or virus. Of 34 genes documented to correct ΔF508 trafficking, 9 were directly linked by positive expression activation mechanisms to the immune inflammatory response. Looking at interactions among the results as a whole and in detail, it is apparent that an inflammatory response produces numerous changes which favor correct trafficking of ΔF508. One can take a view of the inflammatory process as potentially a corrective mechanism for dysfunctional ΔF508 trafficking. This opens up a new research direction and provides new targets in the search for disease treatments.
authors.forename: Jerry Mobley
authors.initials: JM
authors.lastname: Wright
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Joseloff
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.forename: Tatiana
authors.initials: T
authors.lastname: Serebriyskaya
authors.forename: Diana
authors.initials: D
authors.lastname: Wetmore