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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 (?F508) 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 ?F508 trafficking and a list of genes differentially expressed in bronchial epithelial cells after exposure to bacteria or virus. Of 34 genes documented to correct ?F508 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 ?F508. One can take a view of the inflammatory process as potentially a corrective mechanism for dysfunctional ?F508 trafficking. This opens up a new research direction and provides new targets in the search for disease treatments.

SUBMITTER: Wright JM

PROVIDER: S-EPMC3055700 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Interactions between an inflammatory response to infection and protein trafficking pathways favor correction of defective protein trafficking in Cystic Fibrosis.

Wright Jerry Mobley JM Joseloff Elisabeth E Nikolsky Yuri Y Serebriyskaya Tatiana T Wetmore Diana D

Bioinformation 20101127 6

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 ...[more]

PMID: 21364822

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Project description:Interactions in the airway ecology of cystic fibrosis may alter organism persistence and clinical outcomes. Better understanding of such interactions could guide clinical decisions. We used generalized estimating equations to fit logistic regression models to longitudinal 2-year patient cohorts in the Cystic Fibrosis Foundation Patient Registry, 2003 to 2011, in order to study associations between the airway organisms present in each calendar year and their presence in the subsequent year. Models were adjusted for clinical characteristics and multiple observations per patient. Adjusted models were tested for sensitivity to cystic fibrosis-specific treatments. The study included 28,042 patients aged 6 years and older from 257 accredited U.S. care centers and affiliates. These patients had produced sputum specimens for at least two consecutive years that were cultured for methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Candida and Aspergillus species. We analyzed 99.8% of 538,458 sputum cultures from the patients during the study period. Methicillin-sensitive S. aureus was negatively associated with subsequent Paeruginosa. Paeruginosa was negatively associated with subsequent B. cepacia complex, Axylosoxidans, and Smaltophilia. Bcepacia complex was negatively associated with the future presence of all bacteria studied, as well as with that of Aspergillus species. Paeruginosa, B. cepacia complex, and S. maltophilia were each reciprocally and positively associated with Aspergillus species. Independently of patient characteristics, the organisms studied interact and alter the outcomes of treatment decisions, sometimes in unexpected ways. By inhibiting P. aeruginosa, methicillin-sensitive S. aureus may delay lung disease progression. Paeruginosa and B. cepacia complex may inhibit other organisms by decreasing airway biodiversity, potentially worsening lung disease.

Dataset Information

Interactions between an inflammatory response to infection and protein trafficking pathways favor correction of defective protein trafficking in Cystic Fibrosis.

Publications

Interactions between an inflammatory response to infection and protein trafficking pathways favor correction of defective protein trafficking in Cystic Fibrosis.

Similar Datasets

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