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University of Oldenburg
07.12.2022 23:54:44
Seminar: 6.04.150.005 Immunology - Novel Kappa-Opioid-Receptor Agonists (KORA) for the treatment of inflammation - Details
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General information

Course name Seminar: 6.04.150.005 Immunology - Novel Kappa-Opioid-Receptor Agonists (KORA) for the treatment of inflammation
Subtitle
Course number 6.04.150.005
Semester SoSe2022
Current number of participants 1
expected number of participants 2
Home institute Department of Human Medicine
Courses type Seminar in category Teaching
Type/Form
Lehrsprache englisch
ECTS points 15

Course location / Course dates

Please contact Dr. Nadine Mykicki for individual timing and further information (during office hours or by e-mail).

Comment/Description

Objectives
The endogenous opioid system plays an important role in the pathogenesis of inflammatory disorders and opioid receptor agonists, mainly agonists of the kappa-opioid receptor (KOR), are able to regulate cytokine production, immune cell activation and migration. Therefore, activation of KOR could represent a novel promising approach for the treatment of (sterile) inflammation. Therefore, we developed quinoline- and quinoxaline-based KOR agonists with high affinity, selectivity, and full agonistic activity. These KOR agonists reduced the production of pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF, IFN-y) as well as immune cell proliferation upon activation. The observed effects were mediated via KOR signalling, since off-target effects were excluded by using KOR deficient mouse mutants.
Now we intend to develop new KOR agonists based on novel scaffolds. In particular, diverse substituents in 4- or 5-position of the perhydroquinoline system allow versatile modifications allowing fine-tuning of pharmacodynamic and pharmacokinetic properties. These novel KOR agonists will be used to better understand the relevance of KOR signalling in inflammatory diseases. Hence, the effect of KOR agonists on phenotype, function and migratory activity will be analyzed in primary mouse and human immune cells by multicolor flow cytometry, multiplex bead assays or impedance-based measurements using the xCELLigence®-system). Moreover, the metabolic activity and transcription profile of immune cells treated with KOR agonists shall be assessed using the Seahorse® technology and (single cell) RNA sequencing.

Admission settings

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