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 re...
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doaj-27ee54f41b2d4da08f22d4002b2f76522020-11-25T01:55:15ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-05-012011265210.3390/ijms20112652ijms20112652Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific EffectsYasuhiro Ishihara0Sarah Y. Kado1Christiane Hoeper2Shelly Harel3Christoph F. A. Vogel4Center for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USAHere, 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<sup>−/−</sup>) 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<sup>−/−</sup> mice but not in BMM derived from RelB<sup>−/−</sup> 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.https://www.mdpi.com/1422-0067/20/11/2652AhRcytokinesDCIDONF-κB RelBTCDD |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yasuhiro Ishihara Sarah Y. Kado Christiane Hoeper Shelly Harel Christoph F. A. Vogel |
spellingShingle |
Yasuhiro Ishihara Sarah Y. Kado Christiane Hoeper Shelly Harel Christoph F. A. Vogel Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects International Journal of Molecular Sciences AhR cytokines DC IDO NF-κB RelB TCDD |
author_facet |
Yasuhiro Ishihara Sarah Y. Kado Christiane Hoeper Shelly Harel Christoph F. A. Vogel |
author_sort |
Yasuhiro Ishihara |
title |
Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects |
title_short |
Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects |
title_full |
Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects |
title_fullStr |
Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects |
title_full_unstemmed |
Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects |
title_sort |
role of nf-kb relb in aryl hydrocarbon receptor-mediated ligand specific effects |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-05-01 |
description |
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<sup>−/−</sup>) 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<sup>−/−</sup> mice but not in BMM derived from RelB<sup>−/−</sup> 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. |
topic |
AhR cytokines DC IDO NF-κB RelB TCDD |
url |
https://www.mdpi.com/1422-0067/20/11/2652 |
work_keys_str_mv |
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