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

Academic Article

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 glycosylation enzymes. In conclusion, the CFTR genotype changes the expression of multiple genes at baseline and in response to bacterial challenge, and only a subset of these changes is secondary to IL-10 deficiency. © 2004 The American Society of Gene Therapy.
  • Digital Object Identifier (doi)

    Pubmed Id

  • 26302050
  • Author List

  • Virella-Lowell I; Herlihy JD; Liu B; Lopez C; Cruz P; Muller C; Baker HV; Flotte TR
  • Start Page

  • 562
  • End Page

  • 573
  • Volume

  • 10
  • Issue

  • 3