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PublicationHuman-Based Immune Responsive In Vitro Infection Models for Validation of Novel TLR4 Antagonists Identified by Computational DiscoveryInfectious diseases are still a major problem worldwide. This includes microbial infections, with a constant increase in resistance to the current anti-infectives employed. Toll-like receptors (TLRs) perform a fundamental role in pathogen recognition and activation of the innate immune response. Promising new approaches to combat infections and inflammatory diseases involve modulation of the host immune system via TLR4. TLR4 and its co-receptors MD2 and CD14 are required for immune response to fungal and bacterial infection by recognition of microbial cell wall components, making it a prime target for drug development. To evaluate the efficacy of anti-infective compounds early on, we have developed a series of human-based immune responsive infection models, including immune responsive 3D-skin infection models for modeling fungal infections. By using computational methods: pharmacophore modeling and molecular docking, we identified a set of 46 potential modulators of TLR4, which were screened in several tests systems of increasing complexity, including immune responsive 3D-skin infection models. We could show a strong suppression of cytokine and chemokine response induced by lipopolysacharide (LPS) and Candida albicans for individual compounds. The development of human-based immune responsive assays provides a more accurate and reliable basis for development of new anti-inflammatory or immune-modulating drugs.
PublicationOn-line monitoring of drinking water based on a biological broad-spectrum sensor
PublicationControl of drinking water by linking biosensors with physicochemical methodsAn alarm system is developed for the direct detection of toxic substances in drinking water. The vitality of living organisms or cells is monitored continuously by electrochemical and infrared spectroscopic methods. Mammalian cells or bacteria are acting as highly sensitive biosensors and are monitored simultaneously by infrared and electro-chemical techniques. It enables the nonspecific detection of toxins with short response times for implementation in water supplies.