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Title (Primary) Non-genomic AhR-signaling modulates the immune response in endotoxin-activated macrophages after activation by the environmental stressor BaP
Author Großkopf, H.; Walter, K.; Karkossa, I.; von Bergen, M.; Schubert, K.;
Journal Frontiers in Immunology
Year 2021
Department MOLSYB;
Volume 12
Language englisch;
POF III (all) F11;
Supplements https://ndownloader.figstatic.com/files/27381989
https://ndownloader.figstatic.com/files/27381992
Keywords Aryl hydrocarbon receptor (Ah receptor or AhR), Macrophages, Proteome, Ubiquitin (Ub), Phosphorylation, Immunomodulation, Rac1, Akt
Abstract Emerging studies revealed that the Aryl hydrocarbon receptor (AhR), a receptor sensing environmental contaminants, is executing an immunomodulatory function. However, it is an open question to which extent this is achieved by its role as a transcription factor or via non-genomic signaling. We utilized a multi-post-translational modification-omics approach to examine non-genomic AhR-signaling after activation with endogenous (FICZ) or exogenous (BaP) ligand in endotoxin-activated (LPS) monocyte-derived macrophages. While AhR activation affected abundances of few proteins, regulation of ubiquitination and phosphorylation were highly pronounced. Although the number and strength of effects depended on the applied AhR-ligand, both ligands increased ubiquitination of Rac1, which participates in PI3K/AKT-pathway-dependent macrophage activation, resulting in a pro-inflammatory phenotype. In contrast, co-treatment with BaP and LPS revealed a decreased AKT activity mediating an anti-inflammatory effect. Thus, our data show an immunomodulatory effect of AhR activation through a Rac1-ubiquitination dependent mechanism that attenuated AKT-signaling, resulting in a mitigated inflammatory response.
ID 23840
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=23840
Großkopf, H., Walter, K., Karkossa, I., von Bergen, M., Schubert, K. (2021):
Non-genomic AhR-signaling modulates the immune response in endotoxin-activated macrophages after activation by the environmental stressor BaP
Front. Immunol. 12 , art. 620270