title: Interleukin-4 Induces CpG Site-Specific Demethylation of the Pendrin Promoter in Primary Human Bronchial Epithelial Cells.
abstract: Pendrin is upregulated in bronchial epithelial cells following IL-4 stimulation via binding of STAT6 to an N4 GAS motif. Basal CpG methylation of the pendrin promoter is cell-specific. We studied if a correlation exists between IL-4 sensitivity and the CpG methylation status of the pendrin promoter in human bronchial epithelial cell models.
  
  
  METHODS
  Real-time PCR and pyrosequencing were used to respectively quantify pendrin mRNA levels and methylation of pendrin promoter, with and without IL-4 stimulation, in healthy and diseased primary HBE cells, as well as NCI-H292 cells.
  
  
  RESULTS
  Increases in pendrin mRNA after IL-4 stimulation was more robust in NCI-H292 cells than in primary cells. The amount of gDNA methylated varied greatly between the cell types. In particular, CpG site 90 located near the N4 GAS motif was highly methylated in the primary cells. An additional CpG site (90bis), created by a SNP, was found only in the primary cells. IL-4 stimulation resulted in dramatic demethylation of CpG sites 90 and 90bis in the primary cells.
  
  
  CONCLUSIONS
  IL-4 induces demethylation of specific CpG sites within the pendrin promoter. These epigenetic alterations are cell type specific, and may in part dictate pendrin mRNA transcription.
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Giada
authors.initials: G
authors.lastname: Scantamburlo
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Vanoni
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dossena
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Selma M
authors.initials: SM
authors.lastname: Soyal
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bernardinelli
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Davide Antonio
authors.initials: DA
authors.lastname: Civello
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
authors.affiliation: Center for Health & Bioresources, Austrian Institute of Technology (AIT), Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
authors.affiliation: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Charity
authors.initials: C
authors.lastname: Nofziger
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D000076988:Sulfate Transporters
chemical_list: C508598:IL4 protein, human; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D015847:Interleukin-4
keywords: Asthma; COPD; Lung; SLC26A4; STAT6