ReIB, a new partner of aryl hydrocarbon receptor-mediated transcription

The nuclear factor-kappa B (NF-kappa B) transcription factor family has a crucial role in rapid responses to stress and pathogens. We show that the NF-kappa B subunit ReIB 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. ReIB physically interacts with AhR and binds to an unrecognized ReIB/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 ReIB/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-kappa B-binding sites that are preferentially recognized by ReIB/p52 are a target for ReIB/AhR complexes without addition of any stimuli, implicating the endogenous function of the AhR. ReIB/AhR complexes are also found to bind on xenobiotic responsive element, and ReIB drastically increases the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced xenobiotic responsive element reporter activity. The interaction of ReIB with AhR signaling, and AhR with NF-kappa B ReIB signaling pathways represent a new mechanism of cross talk between the two transcription factors.