Immunopharmacology and inflammationAuraptene has the inhibitory property on murine T lymphocyte activation

Auraptene, a citrus fruit-derived coumarin, has been reported to exert valuable pharmacological properties as anti-tumor, anti-inflammatory, and anti-oxidant agent. However, little is known about auraptene on immune responses. In this study, we conducted an investigation to evaluate auraptene as an anti-T lymphocyte proliferation agent using CD3/CD28-activated lymphocytes isolated from C57BL/6 mice. We found that administration of auraptene inhibited CD3/CD28-activated lymphocyte proliferation in a dose dependent manner, but the inhibition at a wide range of doses used in this study did not induce cytotoxicity or apoptosis. In addition, auraptene dose dependently decreased the CD3/CD28-activated T lymphocyte secreting T helper (Th)1 cytokines (interleukin (IL)-2 and interferon (IFN)-γ); whereas, auraptene could decrease Th2 cytokine (IL-4) at a higher level (40 µM) but had not at lower levels (10 and 20 µM). Further mechanistic study demonstrated that auraptene doses dependently suppressed T cell early and middle/late activation marker CD69 and CD25 expression, respectively. Finally, auraptene could suppress cell cycle progression which contributes to inhibiting T cell proliferation and cell division. These findings indicate that auraptene exhibits anti-inflammatory properties via inhibiting T cell proliferation and their inflammatory cytokine secretion that may mediate the interaction between T cells and autoimmune disorders, suggesting that auraptene is a potential food-derived compound with a benefit to those with abnormally over-activation T cell mediated response and chronic inflammation such as autoimmune and inflammatory diseases.