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Referenztyp Zeitschriften
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Creative Commons Lizenz creative commons licence
Titel (primär) Proteomic characterization of the cellular effects of AhR activation by microbial tryptophan catabolites in endotoxin-activated human macrophages
Autor Walter, K.; Grosskopf, H.; Karkossa, I.; von Bergen, M.; Schubert, K.;
Journal / Serie International Journal of Environmental Research and Public Health
Erscheinungsjahr 2021
Department MOLSYB;
Band/Volume 18
Heft 19
Sprache englisch;
Supplements https://www.mdpi.com/1660-4601/18/19/10336/s1
Keywords AhR; macrophages; proteome; BaP; indoles; indole-3-acetic acid; indole-3-aldehyde; LPS
Abstract Sensing microbial tryptophan catabolites by the aryl hydrocarbon receptor (AhR) plays a pivotal role in host-microbiome homeostasis by modulating the host immune response. Nevertheless, the involved cellular processes triggered by the metabolites are mainly unknown. Here, we analyzed proteomic changes in macrophages after treatment with the tryptophan metabolites indole-3-acetic acid (I3AA) or indole-3-aldehyde (IAld), as well as the prototypic exogenous AhR-ligand benzo(a)pyrene (BaP) in the absence and presence of lipopolysaccharide (LPS) to identify affected cellular processes and pathways. The AhR-ligands regulated metabolic and immunologic processes in dependency of LPS co-stimulation. All investigated ligands time-dependently enhanced fatty acid β-oxidation. Differences due to the combination with LPS were observed for all three ligands. Additionally, oxidative phosphorylation was significantly increased by IAld and I3AA in a time and LPS-dependent manner. Immunoregulatory processes were affected in distinct ways. While BaP and I3AA up-regulated IL-8 signaling, IL-6 signaling was decreased by IAld. BaP decreased the inflammasome pathway. Thus, AhR-ligand-dependent regulations were identified, which may modulate the response of macrophages to bacterial infections, but also the commensal microbiota through changes in immune cell signaling and metabolic pathways that may also alter functionality. These findings highlight the relevance of AhR for maintaining microbial homeostasis and, consequently, host health.
ID 25159
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25159
Walter, K., Grosskopf, H., Karkossa, I., von Bergen, M., Schubert, K. (2021):
Proteomic characterization of the cellular effects of AhR activation by microbial tryptophan catabolites in endotoxin-activated human macrophages
Int. J. Environ. Res. Public Health 18 (19), 10336