期刊
FASEB JOURNAL
卷 23, 期 9, 页码 3078-3088出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.09-129312
关键词
aptamer microarray; microbial infection; IP-SELEX
资金
- National Science Council [NSC-96-2628-B-001-024-MY3]
- Department of Health, and Academia Sinica, Taipei, Taiwan, ROC
Toll-like receptors (TLRs) play important roles in the immune responses against invading microorganisms. Development of TLR antagonists is recognized as a promising direction in suppressing the associated inflammatory reactions of the TLRs. Aptamers are single-stranded RNA or DNA molecules isolated through an in vitro selection process. Using a novel molecular evolution strategy that combines immuno-precipitation (IP) with systematic evolution of ligands by exponential enrichment (SELEX), we developed an IP-SELEX selection method to facilitate the screening of high-affinity aptamers for the Toll-like receptor 2 (TLR2). Also, human TLR2 functional aptamers were identified and characterized using NF-kappa B reporter assays. Among the functional aptamers, the most effective, AP177, with a dissociation constant of 73 pM, was characterized with TLR2-expressing cells challenged with bacterial cells and purified ligands. The aptamer could effectively antagonize TLR2, significantly inhibit NF-kappa B activity, and suppress the secretion of the cytokines by >80%. In addition, the precise region within the functional aptamer that specifically bound TLR2 was resolved using aptamer microarray analysis. The results of functional assays showed that AP177 acted as a TLR2 antagonist and may hold therapeutic potential in the treatment of diseases related to dysregulated TLR2 immune responses.-Chang, Y.-C., Kao, W.-C., Wang, W.-Y., Wang, W.-Y., Yang, R.-B., Peck, K. Identification and characterization of oligonucleotides that inhibit Toll-like receptor 2-associated immune responses. FASEB J. 23, 3078-3088 ( 2009). www.fasebj.org
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