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, cotreatment
with ligand and LPS revealed a decreased AKT activity mediating an antiinflammatory
effect. Thus, our data show an immunomodulatory effect of AhR activation
through a Rac1ubiquitination-dependent mechanism that attenuated AKT-signaling,
resulting in a mitigated inflammatory response.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84292 |
| Date | 24 March 2023 |
| Creators | Großkopf, Henning, Walter, Katharina, Karkossa, Isabel, von Bergen, Martin, Schubert, Kristin |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-3224, 620270 |
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