The aryl hydrocarbon receptor (AhR) is responsible for the toxic effects of environmental pollutants such as dioxin, but little is known about its normal physiological functions. Li et al. (2011) now show that specific dietary compounds present in cruciferous vegetables act through the AhR to promote intestinal immune function, revealing AhR as a critical link between diet and immunity.
"The contributions of dietary ligands to modulation of dynamic lymphoid tissue in the gut are just beginning to be explored. Mice fed diets free of defined phytochemicals have reduced numbers of both cryptopatches and ILF, implicating a key role for nutrients in maintaining (or disrupting) intestinal inflammatory homeostasis , . We have explored the mechanisms by which dietary ligand GRA induces B cell recruitment to ILF. "
[Show abstract][Hide abstract] ABSTRACT: 18β-glycyrrhetinic acid (GRA) is a pharmacologically active component of licorice root with documented immunomodulatory properties. We reported that GRA administered orally to mice induces B cell recruitment to isolated lymphoid follicles (ILF) in the small intestine and shortens the duration of rotavirus antigen shedding. ILF are dynamic lymphoid tissues in the gut acquired post-natally upon colonization with commensal bacteria and mature through B cell recruitment to the follicles, resulting in up-regulation of IgA synthesis in response to changes in the composition of microbiota. In this study, we investigated potential mechanisms by which GRA induces ILF maturation in the ileum and the colon using mice depleted of enteric bacteria and a select group of mice genetically deficient in pattern recognition receptors. The data show GRA was unable to induce ILF maturation in ileums of mice devoid of commensal bacteria, MyD88-/- or NOD2-/- mice, but differentially induced ILF in colons. Increased expression of chemokine and chemokine receptor genes that modulate B and T cell recruitment to the mucosa were in part dependent on NOD2, TLR, and signaling adaptor protein MyD88. Together the results suggest GRA induces ILF through cooperative signals provided by bacterial ligands under normal conditions to induce B cell recruitment to ILF to the gut, but that the relative contribution of these signals differ between ileum and colon.
PLoS ONE 07/2014; 9(7):e100878. DOI:10.1371/journal.pone.0100878 · 3.23 Impact Factor
"For example, numerous dietary phytochemicals have been shown to bind and/or modulate AHR action, and these include diindolylmethane, indole-3-carbinol (I3C) and its acidic condensation product indolo-[3,2b]carbazole, and various flavonoids, carotenoids and other chemicals –. In fact, recent studies have reported the ability of dietary AHR active compounds present in cruciferous vegetables to promote intestinal immune function, revealing the AHR as a critical link between diet and immunity , . "
[Show abstract][Hide abstract] ABSTRACT: The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of structurally diverse chemicals. In this study, we examined the ability of a series of ginsenosides extracted from ginseng, a traditional Chinese medicine, to bind to and activate/inhibit the AHR and AHR signal transduction. Utilizing a combination of ligand and DNA binding assays, molecular docking and reporter gene analysis, we demonstrated the ability of selected ginsenosides to directly bind to and activate the guinea pig cytosolic AHR, and to stimulate/inhibit AHR-dependent luciferase gene expression in a recombinant guinea pig cell line. Comparative studies revealed significant species differences in the ability of ginsenosides to stimulate AHR-dependent gene expression in guinea pig, rat, mouse and human cell lines. Not only did selected ginsenosides preferentially activate the AHR from one species and not others, mouse cell line was also significantly less responsive to these chemicals than rat and guinea pig cell lines, but the endogenous gene CYP1A1 could still be inducted in mouse cell line. Overall, the ability of these compounds to stimulate AHR signal transduction demonstrated that these ginsenosides are a new class of naturally occurring AHR agonists.
PLoS ONE 06/2013; 8(6):e66258. DOI:10.1371/journal.pone.0066258 · 3.23 Impact Factor
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