Please use this identifier to cite or link to this item: http://dx.doi.org/10.18419/opus-14984
Authors: Merk, Helena
Amran-Gealia, Tehila
Finkelmeier, Doris
Kohl, Christina
Pichota, Isabelle
Stern, Noa
Rupp, Steffen
Goldblum, Amiram
Burger-Kentischer, Anke
Title: Human-based immune responsive in vitro infection models for validation of novel TLR4 antagonists identified by computational discovery
Issue Date: 2022
metadata.ubs.publikation.typ: Zeitschriftenartikel
metadata.ubs.publikation.seiten: 15
metadata.ubs.publikation.source: Microorganisms 10 (2022), No. 243
URI: http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-150032
http://elib.uni-stuttgart.de/handle/11682/15003
http://dx.doi.org/10.18419/opus-14984
ISSN: 2076-2607
Abstract: Infectious 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.
Appears in Collections:04 Fakultät Energie-, Verfahrens- und Biotechnik

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