Aryl hydrocarbon receptor ligand effects in RBL2H3 cells

Kristina Maaetoft-Udsen; Lori M. N. Shimoda; Hanne Frøkiær; Helen Turner

doi:10.3109/1547691X.2012.661802

Aryl hydrocarbon receptor ligand effects in RBL2H3 cells

Kristina Maaetoft-Udsen, Lori M. N. Shimoda, Hanne Frøkiær, Helen Turner

23 Citations (Scopus)

Abstract

The aryl hydrocarbon receptor (AHR) mediates toxic effects of dioxin and xenobiotic metabolism. AHR has an emerging role in the immune system, but its physiological ligands and functional role in immunocytes remain poorly understood. Mast cells are immunocytes that are central to inflammatory responses and release a spectrum of pro-inflammatory mediators including histamine, mast cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. The aim was to investigate the AHR in model mast cells and examine how both putative and known AHR ligands, e.g., kynurenine, kynurenic acid (KA), Resveratrol, indolmycin, and violacein, affect mast cell activation and signaling. These ligands were tested on calcium signaling, degranulation, and gene expression. The data show that AHR is present in three model mast cell lines, and that various known and putative AHR ligands regulate gene expression of Cyp1a1, a gene down-stream of AHR. Furthermore, it was found that calcium influxes and mast cell secretory responses were enhanced or suppressed after chronic treatment with AHR agonists or antagonists, and that AHR ligands modified RBL2H3 cell degranulation. AHR ligands can chronically change cytokine gene expression in activated mast cells, as exemplified by IL-6. The antagonist Resveratrol repressed expression of induced IL-6 gene expression. Although KA and kynurenine are both AHR agonists, these ligands behaved differently in regards to degranulation and IL-6 expression, indicating that they may function outside of AHR pathways. These data suggest considerable complexity in RBL2H3 responses to AHR ligands, with implications for understanding of both dioxin pathology and the immunological effects of endogenous AHR ligands.

Original language	English
Journal	Journal of Immunotoxicology
Volume	9
Issue number	3
Pages (from-to)	327-337
Number of pages	11
ISSN	1547-691X
DOIs	https://doi.org/10.3109/1547691X.2012.661802
Publication status	Published - Jul 2012

Keywords

Animals
Cell Degranulation
Cell Line
Cytochrome P-450 CYP1A1
Dioxins
Gene Expression Regulation
Interleukin-6
Mast Cells
Rats
Receptors, Aryl Hydrocarbon
Signal Transduction
Xenobiotics

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10.3109/1547691X.2012.661802

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title = "Aryl hydrocarbon receptor ligand effects in RBL2H3 cells",

abstract = "The aryl hydrocarbon receptor (AHR) mediates toxic effects of dioxin and xenobiotic metabolism. AHR has an emerging role in the immune system, but its physiological ligands and functional role in immunocytes remain poorly understood. Mast cells are immunocytes that are central to inflammatory responses and release a spectrum of pro-inflammatory mediators including histamine, mast cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. The aim was to investigate the AHR in model mast cells and examine how both putative and known AHR ligands, e.g., kynurenine, kynurenic acid (KA), Resveratrol, indolmycin, and violacein, affect mast cell activation and signaling. These ligands were tested on calcium signaling, degranulation, and gene expression. The data show that AHR is present in three model mast cell lines, and that various known and putative AHR ligands regulate gene expression of Cyp1a1, a gene down-stream of AHR. Furthermore, it was found that calcium influxes and mast cell secretory responses were enhanced or suppressed after chronic treatment with AHR agonists or antagonists, and that AHR ligands modified RBL2H3 cell degranulation. AHR ligands can chronically change cytokine gene expression in activated mast cells, as exemplified by IL-6. The antagonist Resveratrol repressed expression of induced IL-6 gene expression. Although KA and kynurenine are both AHR agonists, these ligands behaved differently in regards to degranulation and IL-6 expression, indicating that they may function outside of AHR pathways. These data suggest considerable complexity in RBL2H3 responses to AHR ligands, with implications for understanding of both dioxin pathology and the immunological effects of endogenous AHR ligands.",

keywords = "Animals, Cell Degranulation, Cell Line, Cytochrome P-450 CYP1A1, Dioxins, Gene Expression Regulation, Interleukin-6, Mast Cells, Rats, Receptors, Aryl Hydrocarbon, Signal Transduction, Xenobiotics, Mast cells, calcium, aryl hydrocarbon receptor, resveratrol, kynurenine",

author = "Kristina Maaetoft-Udsen and Shimoda, {Lori M. N.} and Hanne Fr{\o}ki{\ae}r and Helen Turner",

year = "2012",

month = jul,

doi = "10.3109/1547691X.2012.661802",

language = "English",

volume = "9",

pages = "327--337",

journal = "Journal of Immunotoxicology",

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TY - JOUR

T1 - Aryl hydrocarbon receptor ligand effects in RBL2H3 cells

AU - Maaetoft-Udsen, Kristina

AU - Shimoda, Lori M. N.

AU - Frøkiær, Hanne

AU - Turner, Helen

PY - 2012/7

Y1 - 2012/7

N2 - The aryl hydrocarbon receptor (AHR) mediates toxic effects of dioxin and xenobiotic metabolism. AHR has an emerging role in the immune system, but its physiological ligands and functional role in immunocytes remain poorly understood. Mast cells are immunocytes that are central to inflammatory responses and release a spectrum of pro-inflammatory mediators including histamine, mast cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. The aim was to investigate the AHR in model mast cells and examine how both putative and known AHR ligands, e.g., kynurenine, kynurenic acid (KA), Resveratrol, indolmycin, and violacein, affect mast cell activation and signaling. These ligands were tested on calcium signaling, degranulation, and gene expression. The data show that AHR is present in three model mast cell lines, and that various known and putative AHR ligands regulate gene expression of Cyp1a1, a gene down-stream of AHR. Furthermore, it was found that calcium influxes and mast cell secretory responses were enhanced or suppressed after chronic treatment with AHR agonists or antagonists, and that AHR ligands modified RBL2H3 cell degranulation. AHR ligands can chronically change cytokine gene expression in activated mast cells, as exemplified by IL-6. The antagonist Resveratrol repressed expression of induced IL-6 gene expression. Although KA and kynurenine are both AHR agonists, these ligands behaved differently in regards to degranulation and IL-6 expression, indicating that they may function outside of AHR pathways. These data suggest considerable complexity in RBL2H3 responses to AHR ligands, with implications for understanding of both dioxin pathology and the immunological effects of endogenous AHR ligands.

AB - The aryl hydrocarbon receptor (AHR) mediates toxic effects of dioxin and xenobiotic metabolism. AHR has an emerging role in the immune system, but its physiological ligands and functional role in immunocytes remain poorly understood. Mast cells are immunocytes that are central to inflammatory responses and release a spectrum of pro-inflammatory mediators including histamine, mast cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. The aim was to investigate the AHR in model mast cells and examine how both putative and known AHR ligands, e.g., kynurenine, kynurenic acid (KA), Resveratrol, indolmycin, and violacein, affect mast cell activation and signaling. These ligands were tested on calcium signaling, degranulation, and gene expression. The data show that AHR is present in three model mast cell lines, and that various known and putative AHR ligands regulate gene expression of Cyp1a1, a gene down-stream of AHR. Furthermore, it was found that calcium influxes and mast cell secretory responses were enhanced or suppressed after chronic treatment with AHR agonists or antagonists, and that AHR ligands modified RBL2H3 cell degranulation. AHR ligands can chronically change cytokine gene expression in activated mast cells, as exemplified by IL-6. The antagonist Resveratrol repressed expression of induced IL-6 gene expression. Although KA and kynurenine are both AHR agonists, these ligands behaved differently in regards to degranulation and IL-6 expression, indicating that they may function outside of AHR pathways. These data suggest considerable complexity in RBL2H3 responses to AHR ligands, with implications for understanding of both dioxin pathology and the immunological effects of endogenous AHR ligands.

KW - Animals

KW - Cell Degranulation

KW - Cell Line

KW - Cytochrome P-450 CYP1A1

KW - Dioxins

KW - Gene Expression Regulation

KW - Interleukin-6

KW - Mast Cells

KW - Rats

KW - Receptors, Aryl Hydrocarbon

KW - Signal Transduction

KW - Xenobiotics

KW - Mast cells

KW - calcium

KW - aryl hydrocarbon receptor

KW - resveratrol

KW - kynurenine

U2 - 10.3109/1547691X.2012.661802

DO - 10.3109/1547691X.2012.661802

M3 - Journal article

C2 - 22471748

SN - 1547-691X

VL - 9

SP - 327

EP - 337

JO - Journal of Immunotoxicology

JF - Journal of Immunotoxicology

IS - 3

ER -

Aryl hydrocarbon receptor ligand effects in RBL2H3 cells

Abstract

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