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.
authors.affiliation: Laboratory of Immunology and Signal Transduction, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Maaetoft-Udsen
authors.forename: Lori M N
authors.initials: LM
authors.lastname: Shimoda
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiær
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004147:Dioxins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis; D008407:Mast Cells; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015262:Xenobiotics / Q000494:pharmacology*
chemical_list: D004147:Dioxins; D015850:Interleukin-6; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D019363:Cytochrome P-450 CYP1A1