AhR Reporter HepG2 Cells

The aryl hydrocarborn receptor (AhR) is a ligand-dependent transcriptional factor widely expressed in barrier tissues [1]. AhR plays a key role in gut-microbiota and host’s immune homeostasis, not only in the intestine but also at distant sites [1].
Besides xenobiotics, including the prototypic AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a variety of dietary-derived AhR ligands have been identified, many of which are byproducts of tryptophan (Trp) metabolism [2].

Inactive AhR resides in the cytoplasm within a Hsp90:XAP2:p23:Src protein complex. The AhR canonical genomic signaling pathway occurs as follows: upon ligand binding, the complex undergoes conformational changes and translocates into the nucleus. AhR heterodimerizes with AhR nuclear translocator (ARNT) before binding to dioxin response elements (DREs) in the upstream regulatory regions of AhR target genes, such as the cytochrome P450-dependent monooxygenase Cyp1a1, the AhR repressor (AhRR), and the IL-22 interleukin.

Of note, non-canonical AhR signaling pathways have also been reported, either at the genomic level through association with other transcription factors (e.g. NF-κB), or at the non-genomic level (e.g. through the release of the Src kinase) [2,3].

References

1. Lamas B. et al. 2018. Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunol. 11:1024-38.
2. Gao J. et al. 2018. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front. Cell. Infect. Microbiol. 8:13.
3. Park JH. et al., 2018. Kynurenine promotes the goblet cell differentiation of HT-29 colon carcinoma cells by modulating Wnt, Notch and AhR signals. Oncol Rep. 39(4):1930-8.