title: Influence of the cystic fibrosis transmembrane conductance regulator on expression of lipid metabolism-related genes in dendritic cells.
abstract: BACKGROUND
  Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Infections of the respiratory tract are a hallmark in CF. The host immune responses in CF are not adequate to eradicate pathogens, such as P. aeruginosa. Dendritic cells (DC) are crucial in initiation and regulation of immune responses. Changes in DC function could contribute to abnormal immune responses on multiple levels. The role of DC in CF lung disease remains unknown.
  
  
  METHODS
  This study investigated the expression of CFTR gene in bone marrow-derived DC. We compared the differentiation and maturation profile of DC from CF and wild type (WT) mice. We analyzed the gene expression levels in DC from naive CF and WT mice or following P. aeruginosa infection.
  
  
  RESULTS
  CFTR is expressed in DC with lower level compared to lung tissue. DC from CF mice showed a delayed in the early phase of differentiation. Gene expression analysis in DC generated from naive CF and WT mice revealed decreased expression of Caveolin-1 (Cav1), a membrane lipid raft protein, in the CF DC compared to WT DC. Consistently, protein and activity levels of the sterol regulatory element binding protein (SREBP), a negative regulator of Cav1 expression, were increased in CF DC. Following exposure to P. aeruginosa, expression of 3beta-hydroxysterol-Delta7 reductase (Dhcr7) and stearoyl-CoA desaturase 2 (Scd2), two enzymes involved in the lipid metabolism that are also regulated by SREBP, was less decreased in the CF DC compared to WT DC.
  
  
  CONCLUSIONS
  These results suggest that CFTR dysfunction in DC affects factors involved in membrane structure and lipid-metabolism, which may contribute to the abnormal inflammatory and immune response characteristic of CF.
authors.affiliation: Department of Pediatrics, Weill Cornell Medical College, New York, USA. yax2002@med.cornell.edu
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Xu
authors.forename: Christine
authors.initials: C
authors.lastname: Tertilt
authors.forename: Anja
authors.initials: A
authors.lastname: Krause
authors.forename: Luis E N
authors.initials: LE
authors.lastname: Quadri
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall