title: Identification of cytokines that might enhance the promoter activity of HLA-B27.
abstract: OBJECTIVE
  Although the mechanism by which HLA-B27 induces ankylosing spondylitis is unclear, a minimum threshold of transcription is essential, a process controlled at the promoter. Our aim was to scan the effect of a panel of cytokines on the promoter of the HLA-B27 gene over serial timepoints.
  
  
  METHODS
  The promoter region of B*2705 gene was cloned into a luciferase reporter, stably transfected into HeLa cells, and used to monitor the serial effect of 25 cytokines. Results of HLA-B27 promoter-reporter assays were compared to those of real-time polymerase chain reactions.
  
  
  RESULTS
  After an initial delay, significant activation of the HLA-B27 promoter was observed with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and IFN-beta. While early response of the HLA-B27 promoter was highest with TNF-alpha and IFN-gamma, ultimately the highest activity was observed with IFN-beta.
  
  
  CONCLUSIONS
  The only promoter of HLA-B alleles studied in the past was that of HLA-B7, and always at only a single fixed timepoint of culture. This is the first study to show that activation of HLA-B27 promoter is a sequential event, and that TNF-alpha and IFN-beta are major participants at different timepoints.
authors.affiliation: Rheumatology Division, University of California Los Angeles, Los Angeles, California 90024, USA.
authors.forename: Like
authors.initials: L
authors.lastname: Zhao
authors.forename: Yoly
authors.initials: Y
authors.lastname: Fong
authors.forename: Kaisa
authors.initials: K
authors.lastname: Granfors
authors.forename: Jieruo
authors.initials: J
authors.lastname: Gu
authors.forename: David
authors.initials: D
authors.lastname: Yu
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015796:HLA-B27 Antigen; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma