RelB, a New Partner of Aryl Hydrocarbon Receptor-Mediated Transcription

Abstract

The nuclear factor-kappaB (NF-kappaB) transcription factor family has a crucial role in rapid responses to stress and pathogens. We show that the NF-kappaB subunit RelB is functionally associated with the aryl hydrocarbon receptor (AhR) and mediates transcription of chemokines such as IL-8 via activation of AhR and protein kinase A. RelB physically interacts with AhR and binds to an unrecognized RelB/AhR responsive element of the IL-8 promoter linking two signaling pathways to activate gene transcription. We found a time-dependent recruitment of AhR to the RelB/AhR responsive element site of IL-8 mediated by the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and via activation of protein kinase A. Furthermore, NF-kappaB-binding sites that are preferentially recognized by RelB/p52 are a target for RelB/AhR complexes without addition of any stimuli, implicating the endogenous function of the AhR. RelB/AhR complexes are also found to bind on xenobiotic responsive element, and RelB drastically increases the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced xenobiotic responsive element reporter activity. The interaction of RelB with AhR signaling, and AhR with NF-kappaB RelB signaling pathways represent a new mechanism of cross talk between the two transcription factors.

Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription

“…Besides the 'classical' pathway of AhR, the non-canonical interactions between AhR and RelA, STAT1 are important for the biological functions of AhR. For example, AhR agonists have been shown to repress or transactivate NF-kB response genes 22,[42][43][44][45] . The interaction between AhR and STAT1 is relevant for the abrogation of STAT1 signalling and subsequent Th17 differentiation 46 .…”

Differential NF-κB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance

“…The RelB-p52 dimer drives transcription of genes involved in lymphoid organogenesis (38) that belongs to the category of ''Immune and lymphatic system development and function,'' which is among the strongest regulated cellular functions induced after consumption of dead L. plantarum (Table S5). RelB may associate with the aryl hydrocarbon receptor (AHR) and together regulate responses to nonself molecules (54). The AHR signaling pathway was regulated after consumption of all 3 bacterial preparations suggesting that in the proximal duodenum of healthy humans, RelB-dependent NF-B signaling and AHR signaling may participate in regulating responses to food bacteria, potentially with roles for the NF-B inhibitors A20, I B, BCL3, and SOCS3.…”

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

“…4A, filled bars). AhR induces IL-6 production, in a human monocytic cell line, via cAMP-dependent PKA activation (27). To test whether AhR-induced cAMP correlates with IL-6 secretion, we used the PKA inhibitor Rp-cAMP.…”