PT - JOURNAL ARTICLE AU - Like Zhao AU - Yoly Fong AU - Kaisa Granfors AU - Jieruo Gu AU - David Yu TI - Identification of cytokines that might enhance the promoter activity of HLA-B27. DP - 2008 May 01 TA - The Journal of Rheumatology PG - 862--868 VI - 35 IP - 5 4099 - http://www.jrheum.org/content/35/5/862.short 4100 - http://www.jrheum.org/content/35/5/862.full SO - J Rheumatol2008 May 01; 35 AB - 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. CONCLUSION: 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.