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

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 200 μM GA and 0.1 μM dexamethasone. Cells were incubated (72 h) 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-γ (IFN-γ) 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 200 μM GA and dexamethasone. The levels of IL-4, IL-10, and IFN-γ decreased after treatment with both dexamethasone and GA, but the ratio of IFN-γ/IL-4 (Th1/Th2 balance) increased significantly due to 200 μM 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.