Identification of cytokines that might enhance the promoter activity of HLA-B27.
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.
Zhao
Like
L
Rheumatology Division, University of California Los Angeles, Los Angeles, California 90024, USA.
Fong
Yoly
Y
Granfors
Kaisa
K
Gu
Jieruo
J
Yu
David
D
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*
D015796:HLA-B27 Antigen; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma