Involvement of RelB in aryl hydrocarbon receptor-mediated induction of chemokines.
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 1 (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-kappaB element that is recognized by the NF-kappaB subunit RelB and localized on promoters of the cytokine and chemokine genes BAFF, BLC, CCL1, and the transcription factor IRF3. The interaction of AhR with RelB binding on a novel type of NF-kappaB binding site represents a new regulatory function of the AhR.
Vogel
Christoph F A
CF
Department of Environmental Toxicology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA. cfvogel@ucdavis.edu
Sciullo
Eric
E
Matsumura
Fumio
F
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D054402:Chemokine CCL1 / Q000235:genetics; D018925:Chemokines / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020298:U937 Cells
C497396:ARNT protein, human; D053264:B-Cell Activating Factor; C065971:CCL1 protein, human; D054402:Chemokine CCL1; D018925:Chemokines; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D000072317:Polychlorinated Dibenzodioxins; C497593:RELB protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; C505719:TNFSF13B protein, human; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051841:Transcription Factor RelB