2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known immunotoxic compound affecting the expression of inflammatory genes. We found that TCDD induces the expression of the B-cell activating factor of the tumor necrosis factor family (BAFF), B-lymphocyte chemoattractant (BLC), CC-chemokine ligand I (CCL1), and the transcription factor interferon gamma responsive factor (IFR3) in U937 macrophages in an aryl hydrocarbon receptor- (AhR) and RelB-dependent manner. The induction was associated with increased binding activity of an AhR/RelB complex without participation of ARNT to a NF-kappa B element that is recognized by the NF-kappa B subunit RelB and localized on promoters of the cytokine and chemokine genes BAFF, BLC, CCL 1, and the transcription factor IRF3. The interaction of AhR with RelB binding on a novel type of NF-kappa B binding site represents a new regulatory function of the AhR. (C) 2007 Elsevier Inc. All rights reserved.