Auraptene regulates Th1/Th2/TReg balances, NF-κB nuclear localization and nitric oxide production in normal and Th2 provoked situations in human isolated lymphocytes

Abstract

Background: Auraptene as member of dietary coumarins, is found in citrus fruits. Former studies have demonstrated its anti-inflammatory and anti-cancer activity.

Purpose: The mechanism of action and immune-modulatory property of this compound on human lymphocytes are greatly unknown.

Study design/methods: The effect of three concentrations (10, 30 and 90 µM) of auraptene or dexamethasone (0.1 mM) were evaluated on percentage of cell proliferation and nitric oxide (NO) production as well as secretion and gene expression of cytokines, and NF-κB level in PHA-stimulated and non-stimulated lymphocytes.

Results: In non-stimulated cells, all three concentrations of auraptene significantly increased the gene expression index of IL-10 (P < 0.05-0.001). The IFN-γ gene expression index, IFN-γ/IL-4 and IL-10/IL-4 gene expression ratio were significantly increased due to the high concentration (90 µM) of auraptene treatment compared to control group (P < 0.05-0.001). In PHA stimulation, all three concentrations of the extract significantly decreased proliferation, cytokines (IL-4, IL-10 and IFN-γ) and NF-κB level as well as NO production, but IFN-γ/IL-4 and IL-10/IL-4 ratio were significantly increased compared control group (P < 0.05-0.001). Gene expression of IL-10 and IL-4 was decreased but that of IFN-γ as well as FN-γ/IL-4 and IL-10/IL-4 ratio were significantly increased due to all three concentrations of auraptene.

Conclusion: The results showed promoting effects of auraptene on T cell subsets toward Th₁ (IFN-γ) and T_reg (IL-10), which suggest its therapeutic value for treatment of Th₂ cells predominant diseases including allergic disease such as asthma and atopic dermatitis as well as cancers.

Keywords: Auraptene; IFN-γ; IL-10; ILL-4; Nitric Oxide; Th(1)/Th(2) (IFN-γ/IL-4) balance.