18β-glycyrrhetinic acid delivered orally induces isolated lymphoid follicle maturation at the intestinal mucosa and attenuates rotavirus shedding

Jay M Hendricks; Carol Hoffman; David W Pascual; Michele E Hardy

doi:10.1371/journal.pone.0049491

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18β-glycyrrhetinic acid delivered orally induces isolated lymphoid follicle maturation at the intestinal mucosa and attenuates rotavirus shedding

Journal article

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18β-glycyrrhetinic acid delivered orally induces isolated lymphoid follicle maturation at the intestinal mucosa and attenuates rotavirus shedding

Jay M Hendricks, Carol Hoffman, David W Pascual and Michele E Hardy

PloS one, Vol.7(11), pp.e49491-e49491

2012

DOI: https://doi.org/10.1371/journal.pone.0049491

Handle:

https://hdl.handle.net/2376/112649

PMCID: PMC3496704

PMID: 23152913

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Abstract

Transcription, Genetic - drug effects

Antigens, Viral - metabolism

Leukocyte Common Antigens - metabolism

Intestine, Small - pathology

Virus Shedding - drug effects

Cell Count

Rotavirus - physiology

Rotavirus - immunology

Cell Aggregation - drug effects

Male

Peyer's Patches - drug effects

Lymphoid Tissue - growth & development

Intestinal Mucosa - drug effects

Glycyrrhetinic Acid - pharmacology

T-Lymphocytes - drug effects

Peyer's Patches - virology

Peyer's Patches - pathology

Receptors, Chemokine - genetics

Lymphoid Tissue - drug effects

Syndecan-1 - metabolism

Administration, Oral

Glycyrrhetinic Acid - analogs & derivatives

Lymphoid Tissue - virology

CD3 Complex

Mice, Inbred C57BL

Receptors, Chemokine - metabolism

Glycyrrhetinic Acid - administration & dosage

Intestinal Mucosa - virology

Intestine, Small - virology

Gene Expression Regulation - drug effects

Rotavirus Infections - immunology

B-Lymphocytes - drug effects

Lymphoid Tissue - pathology

Animals

B-Lymphocytes - immunology

Intestine, Small - drug effects

T-Lymphocytes - immunology

Antigens, CD19 - metabolism

Mice

Rotavirus Infections - pathology

Rotavirus - drug effects

Intestinal Mucosa - pathology

Ligands

Glycyrrhizin, an abundant bioactive component of the medicinal licorice root is rapidly metabolized by gut commensal bacteria into 18β-glycyrrhetinic acid (GRA). Either or both of these compounds have been shown to have antiviral, anti-hepatotoxic, anti-ulcerative, anti-tumor, anti-allergenic and anti-inflammatory activity in vitro or in vivo. In this study, the ability of GRA to modulate immune responses at the small intestinal mucosa when delivered orally was investigated. Analysis of cytokine transcription in duodenal and ileal tissue in response to GRA treatment revealed a pattern of chemokine and chemokine receptor gene expression predictive of B cell recruitment to the gut. Consistent with this finding, GRA induced increases in CD19(+) B cells in the lamina propria and B220(+) B cell aggregates framed by CD11c(+) dendritic cells in structures resembling isolated lymphoid follicles (ILF). Using a mouse model of rotavirus infection, GRA reduced the duration of viral antigen shedding, and endpoint serum antibody titers were higher in GRA-treated animals. Together the data suggest GRA delivered orally augments lymphocyte recruitment to the intestinal mucosa and induces maturation of B cell-rich ILF independently of ectopic antigenic stimulus. These results provide further support a role for dietary ligands in modulation of dynamic intestinal lymphoid tissue.

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Title: 18β-glycyrrhetinic acid delivered orally induces isolated lymphoid follicle maturation at the intestinal mucosa and attenuates rotavirus shedding
Creators: Jay M Hendricks - Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America
Carol Hoffman
David W Pascual
Michele E Hardy
Publication Details: PloS one, Vol.7(11), pp.e49491-e49491
Academic Unit: Veterinary Microbiology and Pathology, Department of
Publisher: Public Library Science; United States
Number of pages: 9
Grant note: AT004986 / NCCIH NIH HHS P01 AT004986 / NCCIH NIH HHS GM103500-09 / NIGMS NIH HHS RR020185-09 / NCRR NIH HHS P20 RR020185 / NCRR NIH HHS P20 GM103500 / NIGMS NIH HHS
Identifiers: 99900547547601842
Language: English
Resource Type: Journal article