Effects of CFTR, interleukin-10, and Pseudomonas aeruginosa on gene expression profiles in a CF bronchial epithelial cell Line

Molecular Therapy : the Journal of the American Society of Gene Therapy
Isabel Virella-LowellTerence R Flotte

Abstract

Mutations in CFTR lead to a complex phenotype that includes increased susceptibility to Pseudomonas infections, a functional deficiency of IL-10, and an exaggerated proinflammatory cytokine response. We examined the effects of CFTR gene correction on the gene expression profile of a CF bronchial epithelial cell line (IB3-1) and determined which CF-related gene expression changes could be reversed by IL-10 expression. We performed microarray experiments to monitor the gene expression profile of three cell lines over a time course of exposure to Pseudomonas. At baseline, we identified 843 genes with statistically different levels of expression in CFTR-corrected (S9) cells compared to the IB3-1 line or the IL-10-expressing line. K-means clustering and functional group analysis revealed a primary up-regulation of ubiquitination enzymes and TNF pathway components and a primary down-regulation of protease inhibitors and protein glycosylation enzymes in CF. Key gene expression changes were confirmed by real-time RT-PCR. Massive reprogramming of gene expression occurred 3 h after Pseudomonas exposure. Changes specific to CF included exaggerated activation of cytokines, blunted activation of anti-proteases, and repression of protein gly...Continue Reading

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Citations

Jul 19, 2008·American Journal of Respiratory Cell and Molecular Biology·Toni R Bartling, Mitchell L Drumm
Jan 27, 2009·American Journal of Respiratory Cell and Molecular Biology·Hong YuIsabel Virella-Lowell
Mar 17, 2009·Respiratory Research·Mathilde RottnerM Carmen Martínez
Jan 2, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Thomas H Hampton, Bruce A Stanton
Jul 20, 2010·American Journal of Respiratory Cell and Molecular Biology·Michelle M FarbermanThomas W Ferkol
Aug 10, 2010·American Journal of Respiratory Cell and Molecular Biology·Ashley T MartinoTerence R Flotte
Mar 10, 2012·American Journal of Respiratory Cell and Molecular Biology·Dmitry Ratner, Christian Mueller
Jan 8, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Motohiro TsuchiyaRoopa Biswas
Aug 12, 2009·Journal of Cellular Biochemistry·Michael S Stalvey, Terence R Flotte
Jul 5, 2012·Annals of the New York Academy of Sciences·Jason P EiserichCarroll E Cross
Dec 13, 2005·Free Radical Biology & Medicine·Emilie BoncoeurAlexandra Henrion-Caude
Nov 8, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Olivier TabaryJacky Jacquot
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Oct 22, 2013·Expert Review of Respiratory Medicine·Vignesh VenkatakrishnanMorten Thaysen-Andersen
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Jul 24, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Thomas H HamptonBruce A Stanton
Feb 24, 2006·Pharmacogenetics and Genomics·Rainer BüscherPaul A Insel
Aug 20, 2021·Frontiers in Microbiology·Jian WangNan Yao

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