Identification of Anti-Inflammatory Substances
A Novel HTS Assay
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The immune system of mammals has evolved to eliminate a vast range of pathogenic organisms, but its hyperactivation in acute/chronic inflammatory and autoimmune diseases can pose a threat to the functions of tissues and organs. All inflammatory reactions involve a complex series of intercellular adhesion and signaling events between the immune system and endothelial and tissue-specific cell types. Pathogen associated molecules such as lipopolysaccharids (LPS) of bacterial cell walls are recognized by Toll-like receptors on monocytes, lymphocytes and fibroblasts and activate a signaling cascade which eventually leads to the activation of transcription factors such as activator protein-1 (AP-1), cyclic AMP response element binding protein (CREB) and nuclear factor κB (NFκB). These factors induce the expression of multiple pro-inflammatory genes such as iNOS and COX-2, TNF alpha and IL-1. Due to its pivotal role in all types of inflammatory conditions the NFκB pathway may represent a unique treasure trove for the identification and development of novel pro- and anti-inflammatory drug candidates. For this purpose we have used a commercially available NFκB reporter cell line (Invitrogen) and the Paradigm Detection Platform (Beckman Coulter) to screen secondary bacterial metabolites for their potential to selectively interfere with NFκB transcriptional activity.
Dipl. Biol. Maren Pflüger1, Priv. Doz. Dr. Andreas Eger1, Dr. Christoph Wiesner1, Dr. Jiri Kopecky2, Anita Eigner1, Christian Deinhammer1, Martin Schalling1, Prof. Dr. Wolfgang Schütt1, Dr. Harald Hundsberger1
1 IMC University of Applied Sciences Krems, Austria
2 Czech Academy of Sciences, Nove Hrady, Czech Republic