Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects
Copyright policy )Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects
Here, we investigate the role of RelB in the regulation of genes which were identified to be induced in an aryl hydrocarbon receptor (AhR)-dependent manner and critically involved in regulation of immune responses. We analyzed the expression of genes of the AhR gene battery, cytokines, and immune regulatory enzymes in bone marrow-derived macrophages (BMM) and thymus of B6 wildtype (wt) mice and RelB knockout (RelB−/−) mice after treatment with various AhR ligands. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced expression of indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2 was significantly repressed in thymus of RelB−/− mice but not in BMM derived from RelB−/− mice. Interestingly, the induced and basal expression of the cytokines interleukin (IL)-17A, IL-22, and CCL20 required the functional expression of RelB. The RelB-dependent expression of CCL20 was induced by the AhR ligands TCDD and 6-formylindolo[3,2-b]carbazole (FICZ), whereas indole-3-carbinol (I3C) suppressed CCL20 in lipopolysaccharide (LPS)-activated wt BMM. The LPS-induced expression of IL-6 and IL-10 was enhanced by TCDD and FICZ, whereas I3C significantly suppressed these cytokines in BMM. The exposure to FICZ led to higher increases of IL-17A and IL-22 mRNA compared to the effect of TCDD or I3C in thymus of wt mice. On the other hand, TCDD was the strongest inducer of CYP1A1, AhR Repressor (AhRR), and IDO2. In summary, these findings provide evidence for the important role of RelB in the transcriptional regulation of cytokines and enzymes induced by AhR ligands.
- University of California, San Francisco United States
- University of California, Davis United States
- University of California System United States
- UNIVERSITY OF CALIFORNIA DAVIS
- UNIVERSITY OF CALIFORNIA AT DAVIS
Male, TCDD, 1.1 Normal biological development and functioning, Knockout, 610, Gene Expression, Thymus Gland, Endocrine Disruptors, Ligands, Microbiology, DC, IDO, Immunomodulation, Medicinal and Biomolecular Chemistry, Mice, 616, Receptors, Genetics, Medicinal and biomolecular chemistry, 2.1 Biological and endogenous factors, Animals, NF-κB RelB, Mice, Knockout, Chemical Physics, Inflammatory and immune system, Communication, Macrophages, AhR, Transcription Factor RelB, Biological Sciences, cytokines, NF-B RelB, Gene Expression Regulation, Receptors, Aryl Hydrocarbon, Aryl Hydrocarbon, Agent Orange & Dioxin, Biochemistry and cell biology, Chemical Sciences, Cytokines, Biochemistry and Cell Biology, Other Biological Sciences, Other Chemical Sciences, Protein Binding
Male, TCDD, 1.1 Normal biological development and functioning, Knockout, 610, Gene Expression, Thymus Gland, Endocrine Disruptors, Ligands, Microbiology, DC, IDO, Immunomodulation, Medicinal and Biomolecular Chemistry, Mice, 616, Receptors, Genetics, Medicinal and biomolecular chemistry, 2.1 Biological and endogenous factors, Animals, NF-κB RelB, Mice, Knockout, Chemical Physics, Inflammatory and immune system, Communication, Macrophages, AhR, Transcription Factor RelB, Biological Sciences, cytokines, NF-B RelB, Gene Expression Regulation, Receptors, Aryl Hydrocarbon, Aryl Hydrocarbon, Agent Orange & Dioxin, Biochemistry and cell biology, Chemical Sciences, Cytokines, Biochemistry and Cell Biology, Other Biological Sciences, Other Chemical Sciences, Protein Binding
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