The In Vitro Impact of Glycyrrhizic Acid on CD4+T Lymphocytes through OX40 Receptor in the Patients with Allergic Rhinitis

Abstract

Glycyrrhizic acid (GA), the major bioactive component of glycyrrhiza, possesses anti-inflammatory, anti-allergic, and immunomodulatory activities. This study aimed to investigate the in vitro anti-allergic effect of GA through the OX40 receptor in patients with allergic rhinitis. Purified naive CD4+ T cells of patients with allergic rhinitis (n=12) were activated with anti-CD3/anti-CD28 with and without anti-OX40 agonist mAbs and then treated with 50, 100, and 200M GA and 0.1M dexamethasone. Cells were incubated (72h) to measure cell proliferation. Expression of OX40 in anti-OX40 mAb stimulated CD4+ T cells was evaluated by flow cytometry. mRNA expression of the OX40 receptor and T-bet, GATA-3, and forkhead box P3 (FoxP3) transcriptional factors were measured by a quantitative polymerase chain reaction. The levels of interleukin (IL)-4, IL-10, and interferon- (IFN-) were also measured. GA inhibited significantly the augmented T cell proliferation induced with anti-OX40 mAb. Protein and gene expression of OX40 was also decreased significantly. Dexamethasone and GA inhibited T-bet and GATA-3 genes expression, but this inhibition was only significant for GATA-3. In contrast, enhanced gene expression of FoxP3 was seen using 200M GA and dexamethasone. The levels of IL-4, IL-10, and IFN- decreased after treatment with both dexamethasone and GA, but the ratio of IFN-/IL-4 (Th1/Th2 balance) increased significantly due to 200M GA treatment. This study suggests that GA may have a therapeutic effect on allergic rhinitis, partly by modulation of the Th1/Th2 balance through suppression of OX40 and increasing the activity of regulatory T cells.