TY - JOUR T1 - High-Throughput Screening of Chemical Libraries for Modulators of Gene Promoter Activity of <em>HLA-B2705</em>: Environmental Pathogenesis and Therapeutics of Ankylosing Spondylitis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.101109 SP - jrheum.101109 AU - Like Zhao AU - Chin-Hsiu Liu AU - David Yu Y1 - 2011/04/01 UR - http://www.jrheum.org/content/early/2011/03/30/jrheum.101109.abstract N2 - Objective Ankylosing spondylitis (AS) is a highly heritable disease with HLA-B27 being the strongest susceptible gene. In order to survey the environmental triggers for arthritis development, we used a high-throughput technique to screen the effects of 12,264 chemicals on the HLA-B27 gene promoter. Methods Promoter reporter transfectants 293T-HLA-B27 and HeLa-HLA-B27 were tested using robotics with 12,264 chemicals. Chemicals that modulated HLA-B27 promoter activity &gt; 150% or &lt; 40% were selected for further evaluation of IC50/EC50 and cell viability. Results The primary screening using the 293T-HLA-B27 promoter reporter cell line yielded 5.1% hits that either suppressed (556 chemicals) or enhanced (68 chemicals) the HLA-B27 promoter activity. A secondary reconfirmation screening was carried out with these 624 candidates using HeLa- HLA-B27 promoter reporter cells under several different culture conditions. The yield of positive candidates was 130, of which 47 were derived from natural products. Based on the bio-information of those positive natural products, 21 chemicals were selected for analysis by dose-response IC50/EC50 experiments. Eight compounds showed potential pharmacological activities. Two suppressors are both derived from an herbal medicine (lei gong teng) that has been used for decades to treat immune diseases. The 6 activators all belonged to a group of chemicals known as flavonoids, widely distributed among dietary fruits and vegetables. Conclusion Several common dietary products that contain certain flavonoids might be environmental risk factors for AS; the Chinese traditional herb lei gong teng might be a potential drug for patients who are HLA-B27-positive. These results provide new research directions for the pathogenesis and therapeutics of AS. ER -