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Communication

Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects

1
Center for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USA
2
Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8521, Japan
3
Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2652; https://doi.org/10.3390/ijms20112652
Received: 6 May 2019 / Revised: 24 May 2019 / Accepted: 26 May 2019 / Published: 30 May 2019
(This article belongs to the Special Issue Novel Aspects of Toxicity Mechanisms of Dioxins and Related Compounds)
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. View Full-Text
Keywords: AhR; cytokines; DC; IDO; NF-κB RelB; TCDD AhR; cytokines; DC; IDO; NF-κB RelB; TCDD
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MDPI and ACS Style

Ishihara, Y.; Kado, S.Y.; Hoeper, C.; Harel, S.; Vogel, C.F.A. Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects. Int. J. Mol. Sci. 2019, 20, 2652. https://doi.org/10.3390/ijms20112652

AMA Style

Ishihara Y, Kado SY, Hoeper C, Harel S, Vogel CFA. Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects. International Journal of Molecular Sciences. 2019; 20(11):2652. https://doi.org/10.3390/ijms20112652

Chicago/Turabian Style

Ishihara, Yasuhiro, Sarah Y. Kado, Christiane Hoeper, Shelly Harel, and Christoph F.A. Vogel. 2019. "Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects" International Journal of Molecular Sciences 20, no. 11: 2652. https://doi.org/10.3390/ijms20112652

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