Osthole treatment ameliorates Th2-mediated allergic asthma and exerts immunomodulatory effects on dendritic cell maturation and function

Osthole,an active component of Chinese herbal medicines,reportedly possesses various pharmacological properties and has potential therapeutic applications.This study explored the anti-allergic effects of osthole in asthmatic mice and investigated the immunomodulatory actions of osthole on dendritic cells(DCs)and T cells.Herein,we show that oral administration of osthole to BALB/c mice after ovalbumin(OVA)sensitization ameliorated all of the cardinal features of T helper 2(Th2)-mediated allergic asthma;namely,the production of OVA-specific immunoglobulin E,airway hyperresponsiveness,airway inflammation and the production of Th2-type cytokines including interleukin(IL)-4,IL-5 and IL-13.Surprisingly,IL-10 production was not inhibited and was even enhanced by osthole treatment.We observed a significant increase in the percentages of IL-10-producing DCs and forkhead box P3-positive regulatory T(Treg)cells in osthole-treated asthmatic mice.Additionally,in vitro analyses revealed that osthole-treated bone-marrow-derived DCs had a partial maturation phenotype,secreting large amounts of IL-10 and low levels of proinflammatory cytokines,such as IL-12,IL-6 and tumor necrosis factor-α,and displaying reduced levels of MHC class II surface molecules.These DCs displayed immunosuppressive capacity by directly inhibiting effector T-cell responses or inducing Treg cells.In addition,osthole directly inhibited the activated CD4+T-cell proliferation and Th1/Th2-type cytokine production in this system.Collectively,these results suggest that DCs and T cells are potential target cells responsible for the action of osthole against allergic asthma.